Article

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

THE CASE

Sam C* is a 68-year-old man who presented to his family physician in a rural health clinic due to concerns about weight loss. Since his visit 8 months prior, Mr. C unintentionally had lost 20 pounds. Upon questioning, Mr. C also reported feeling irritable and having difficulty with sleep and concentration.

A review of systems did not indicate the presence of infection or other medical conditions. In the 6 years since becoming a patient to the practice, he had reported no chronic health concerns, was taking no medications, and had only been to the clinic for his annual check-up appointments. He completed a Patient Health Questionnaire (PHQ-9) and scored 18, indicating moderately severe depression.

Mr. C had established care with his physician when he moved to the area from out of state so that he could be closer to his parents, who were in their mid-80s at the time. Mr. C’s physician also had been the family physician for his parents for the previous 20 years. Three years prior to Mr. C’s presentation for weight loss, his mother had received a diagnosis of acute leukemia; she died a year later.

Over the past year, Mr. C had needed to take a more active role in the care of his father, who was now in his early 90s. Mr. C’s father, who was previously in excellent health, had begun to develop significant health problems, including degenerative arthritis and progressive vascular dementia. He also had ataxia, leading to poor mobility, and a neurogenic bladder requiring self-catheterization, which required Mr. C’s assistance. Mr. C lived next door to his father and provided frequent assistance with activities of daily living. However, his father, who always had been the dominant figure in the family, was determined to maintain his independence and not relinquish control to others.

The strain of caregiving activities, along with managing his father’s inflexibility, was causing increasing distress for Mr. C. As he told his family physician, “I just don’t know what to do.”

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

It is estimated that more than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.¹ As individuals with dementia progressively decline, they require increased assistance with activities of daily living (ADLs, such as bathing and dressing) and instrumental activities of daily living (IADLs, such as paying bills and using transportation). Most of this assistance comes from informal caregiving provided by family members and friends.

Caregiver burden can be defined as “the strain or load borne by a person who cares for a chronically ill, disabled, or elderly family member.”² Caregiver stress has been found to be higher for dementia caregiving than other types of caregiving.³ In particular, caring for someone with greater behavioral and psychological symptoms of dementia (BPSDs) has been associated with higher caregiver burden.^4-7

Beyond the subjective burden of care­giving, there are other potential negative ­consequences for dementia caregivers (see ­TABLE 1^8-14 and TABLE 2^15,16). In addition, caregiver distress is related to a number of care recipient outcomes, including earlier institutionalization, more hospitalizations, more BPSDs, poorer quality of life, and greater likelihood of experiencing elder abuse.¹⁷

Assessment, reassessment are key to meeting needs

Numerous factors can foster caregiver well-­being, including feelings of accomplishment and contribution, a strengthening of the relationship with the care recipient, and feeling supported by friends, family, and formal care systems.^18,19 Family physicians can play an important role by assessing and supporting patients with dementia and their caregivers. Ideally, the individual with dementia and the caregiver will be assessed both together and separately.

Caregiver distress is related to care recipient outcomes, such as earlier institutionalization, more hospitalizations, and poorer quality of life.

A thorough assessment includes gathering information about the context and quality of the caregiving relationship; caregiver perception of the care recipient’s health and functional status; caregiver values and preferences; caregiver well-being (including mental health assessment); caregiver skills, abilities, and knowledge about caregiving; and positive and negative consequences of caregiving.²⁰ Caregiver needs—including informational, care support, emotional, physical, and social needs—also should be assessed.

Continue to: Tools are available...

Tools are available to facilitate caregiver assessment. For example, the Zarit Burden Interview is a 22-item self-report measure that can be given to the caregiver²¹; shorter versions (4 and 12 items) are also available.²² Another resource available for caregiver assessment guidance is a toolkit developed by the Family Caregiver Alliance.²⁰

Continually assess for changing needs

As the condition of the individual with dementia progresses, it will be important to reassess the caregiver, as stressors and needs will change over the course of the caregiving relationship. Support should be adapted ­accordingly.

In the early stage of dementia, caregivers may need information on disease progression and dementia care planning, ways to navigate the health care system, financial planning, and useful resources. Caregivers also may need emotional support to help them adapt to the role of caregiver, deal with denial, and manage their stress.^23,24

With dementia progression, caregivers may need support related to increased decision-making responsibility, managing challenging behaviors, assisting with ADLs and IADLs, and identifying opportunities to meet personal social and well-being needs. They also may need support to accept the changes they are seeing in the individual with dementia and the shifts they are experiencing in their relationship with him or her.^23,25

In late-stage dementia, caregiver needs tend to shift to determining the need for long-term care placement vs staying at home, end-of-life planning, loneliness, and anticipatory grief.^23,26 Support with managing changing and accumulating stress typically remains a primary need throughout the progression of dementia.²⁷

Continue to: Specific populations have distinct needs

Specific populations have distinct needs. Some caregivers, including members of the LGBTQ+ community and different racial and ethnic groups, as well as caregivers of people with younger-onset dementia, may have additional support needs.²⁸

More than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.

For example, African American and ­Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-­intensive care, but use fewer formal support services than White caregivers.²⁹ Caregivers from non-White racial and ethnic groups also are more likely to experience discrimination when interacting with health care services on behalf of care recipients.³⁰

Having an awareness of potential specialized needs may help to prevent or address potential care disparities, and cultural humility may help to improve caregiver experiences with primary care physicians.

Resources to support caregivers

Family physicians are well situated to provide informational and emotional support for both patients with dementia and their informal care providers.³¹ Given the variability of caregiver concerns, multicomponent interventions addressing informational, self-care, social support, and financial needs often are needed.³¹ Supportive counseling and psychoeducation can help dementia caregivers with stress management, self-care, coping, and skills training—supporting the development of self-efficacy.^32,33

Outside resources. Although significant caregiver support can be provided directly by the physician, caregivers should be connected with outside resources, including support groups, counselors, psychotherapists, financial and legal support, and formal care services.³⁴

Continue to: Psychosocial and complementary interventions

Psychosocial and complementary interventions. Various psychosocial interventions (eg, psychoeducation, cognitive behavioral therapy, support groups) have been found to be beneficial in alleviating caregiver symptoms of depression, anxiety, and stress and improving well-being, perceived burden, and quality of life. However, systematic reviews have found variability in the degree of helpfulness of these interventions.^35,36

Some caregivers and care recipients may benefit from complementary and integrative medicine referrals. Mind–body therapies such as mindfulness, yoga, and Tai Chi have shown some beneficial effects.³⁷

Online resources. Caregivers also can be directed to online resources from organizations such as the Alzheimer’s Association (www.alz.org), the National Institutes of Health (www.alzheimers.gov), and the Family Caregiver Alliance (www.caregiver.org).

In rural settings, such as the one in which this case took place, online resources may decrease some barriers to supporting caregivers.³⁸ Internet-based interventions also have been found to have some benefit for dementia caregivers.^31,39

However, some rural locations continue to have limited reliable Internet services.⁴⁰ In affected areas, a strong relationship with a primary care physician may be even more important to the well-being of caregivers, since other support services may be less accessible.⁴¹

Continue to: Impacts of the pandemic

Impacts of the pandemic. Although our case took place prior to the COVID-19 pandemic, it is important to acknowledge ways the pandemic has impacted informal dementia caregiving.

Caregiver stress, depression, and anxiety increased during the pandemic, and the need for greater home confinement and social ­distancing amplified the negative impact of social isolation, including loneliness, on ­caregivers.^42,43 Caregivers often needed to increase their caregiving responsibilities and had more difficulty with care coordination due to limited access to in-person resources.⁴³ The pandemic led to increased reliance on technology and telehealth in the support of dementia caregivers.⁴³

THE CASE

The physician prescribed mirtazapine for Mr. C, titrating the dose as needed to address depressive symptoms and promote weight gain. The physician connected Mr. C’s father with home health services, including physical therapy for fall risk reduction. Mr. C also hired part-time support to provide additional assistance with ADLs and IADLs, allowing Mr. C to have time to attend to his own needs. Though provided with information about a local caregiver support group, Mr. C chose not to attend. The physician also assisted the family with advanced directives.

African American and Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-intensive care, but they tend to use fewer formal support services than White caregivers.

A particular challenge that occurred during care for the family was addressing Mr. C’s father’s driving capacity, considering his strong need for independence. To address this concern, a family meeting was held with Mr. C, his father, and his siblings from out of town. Although Mr. C’s father was not willing to relinquish his driver’s license during that meeting, he agreed to complete a functional driving assessment.

The physician continued to meet with Mr. C and his father together, as well as with Mr. C individually, to provide supportive counseling as needed. As the father’s dementia progressed and it became more difficult to complete office appointments, the physician transitioned to home visits to provide care until the father’s death.

After the death of Mr. C’s father, the physician continued to serve as Mr. C’s primary care provider.

Keeping the “family”in family medicine

Through longitudinal assessment, needs identification, and provision of relevant information, emotional support, and resources, family physicians can provide care that can improve the quality of life and well-being and help alleviate burden experienced by dementia caregivers. Family physicians also are positioned to provide treatments that can address the negative physical and psychological health outcomes associated with informal dementia caregiving. By building relationships with multiple family members across generations, family physicians can understand the context of caregiving dynamics and work together with individuals with dementia and their caregivers throughout disease progression, providing consistent support to the family unit.

CORRESPONDENCE
Kathleen M. Young, PhD, MPH, Novant Health Family Medicine Wilmington, 2523 Delaney Avenue, Wilmington, NC 28403; Kathleen.Young@novanthealth.org

THE CASE

Sam C* is a 68-year-old man who presented to his family physician in a rural health clinic due to concerns about weight loss. Since his visit 8 months prior, Mr. C unintentionally had lost 20 pounds. Upon questioning, Mr. C also reported feeling irritable and having difficulty with sleep and concentration.

A review of systems did not indicate the presence of infection or other medical conditions. In the 6 years since becoming a patient to the practice, he had reported no chronic health concerns, was taking no medications, and had only been to the clinic for his annual check-up appointments. He completed a Patient Health Questionnaire (PHQ-9) and scored 18, indicating moderately severe depression.

Mr. C had established care with his physician when he moved to the area from out of state so that he could be closer to his parents, who were in their mid-80s at the time. Mr. C’s physician also had been the family physician for his parents for the previous 20 years. Three years prior to Mr. C’s presentation for weight loss, his mother had received a diagnosis of acute leukemia; she died a year later.

Over the past year, Mr. C had needed to take a more active role in the care of his father, who was now in his early 90s. Mr. C’s father, who was previously in excellent health, had begun to develop significant health problems, including degenerative arthritis and progressive vascular dementia. He also had ataxia, leading to poor mobility, and a neurogenic bladder requiring self-catheterization, which required Mr. C’s assistance. Mr. C lived next door to his father and provided frequent assistance with activities of daily living. However, his father, who always had been the dominant figure in the family, was determined to maintain his independence and not relinquish control to others.

The strain of caregiving activities, along with managing his father’s inflexibility, was causing increasing distress for Mr. C. As he told his family physician, “I just don’t know what to do.”

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

It is estimated that more than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.¹ As individuals with dementia progressively decline, they require increased assistance with activities of daily living (ADLs, such as bathing and dressing) and instrumental activities of daily living (IADLs, such as paying bills and using transportation). Most of this assistance comes from informal caregiving provided by family members and friends.

Caregiver burden can be defined as “the strain or load borne by a person who cares for a chronically ill, disabled, or elderly family member.”² Caregiver stress has been found to be higher for dementia caregiving than other types of caregiving.³ In particular, caring for someone with greater behavioral and psychological symptoms of dementia (BPSDs) has been associated with higher caregiver burden.^4-7

Beyond the subjective burden of care­giving, there are other potential negative ­consequences for dementia caregivers (see ­TABLE 1^8-14 and TABLE 2^15,16). In addition, caregiver distress is related to a number of care recipient outcomes, including earlier institutionalization, more hospitalizations, more BPSDs, poorer quality of life, and greater likelihood of experiencing elder abuse.¹⁷

Assessment, reassessment are key to meeting needs

Numerous factors can foster caregiver well-­being, including feelings of accomplishment and contribution, a strengthening of the relationship with the care recipient, and feeling supported by friends, family, and formal care systems.^18,19 Family physicians can play an important role by assessing and supporting patients with dementia and their caregivers. Ideally, the individual with dementia and the caregiver will be assessed both together and separately.

Caregiver distress is related to care recipient outcomes, such as earlier institutionalization, more hospitalizations, and poorer quality of life.

A thorough assessment includes gathering information about the context and quality of the caregiving relationship; caregiver perception of the care recipient’s health and functional status; caregiver values and preferences; caregiver well-being (including mental health assessment); caregiver skills, abilities, and knowledge about caregiving; and positive and negative consequences of caregiving.²⁰ Caregiver needs—including informational, care support, emotional, physical, and social needs—also should be assessed.

Continue to: Tools are available...

Tools are available to facilitate caregiver assessment. For example, the Zarit Burden Interview is a 22-item self-report measure that can be given to the caregiver²¹; shorter versions (4 and 12 items) are also available.²² Another resource available for caregiver assessment guidance is a toolkit developed by the Family Caregiver Alliance.²⁰

Continually assess for changing needs

As the condition of the individual with dementia progresses, it will be important to reassess the caregiver, as stressors and needs will change over the course of the caregiving relationship. Support should be adapted ­accordingly.

In the early stage of dementia, caregivers may need information on disease progression and dementia care planning, ways to navigate the health care system, financial planning, and useful resources. Caregivers also may need emotional support to help them adapt to the role of caregiver, deal with denial, and manage their stress.^23,24

With dementia progression, caregivers may need support related to increased decision-making responsibility, managing challenging behaviors, assisting with ADLs and IADLs, and identifying opportunities to meet personal social and well-being needs. They also may need support to accept the changes they are seeing in the individual with dementia and the shifts they are experiencing in their relationship with him or her.^23,25

In late-stage dementia, caregiver needs tend to shift to determining the need for long-term care placement vs staying at home, end-of-life planning, loneliness, and anticipatory grief.^23,26 Support with managing changing and accumulating stress typically remains a primary need throughout the progression of dementia.²⁷

Continue to: Specific populations have distinct needs

Specific populations have distinct needs. Some caregivers, including members of the LGBTQ+ community and different racial and ethnic groups, as well as caregivers of people with younger-onset dementia, may have additional support needs.²⁸

More than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.

For example, African American and ­Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-­intensive care, but use fewer formal support services than White caregivers.²⁹ Caregivers from non-White racial and ethnic groups also are more likely to experience discrimination when interacting with health care services on behalf of care recipients.³⁰

Having an awareness of potential specialized needs may help to prevent or address potential care disparities, and cultural humility may help to improve caregiver experiences with primary care physicians.

Resources to support caregivers

Family physicians are well situated to provide informational and emotional support for both patients with dementia and their informal care providers.³¹ Given the variability of caregiver concerns, multicomponent interventions addressing informational, self-care, social support, and financial needs often are needed.³¹ Supportive counseling and psychoeducation can help dementia caregivers with stress management, self-care, coping, and skills training—supporting the development of self-efficacy.^32,33

Outside resources. Although significant caregiver support can be provided directly by the physician, caregivers should be connected with outside resources, including support groups, counselors, psychotherapists, financial and legal support, and formal care services.³⁴

Continue to: Psychosocial and complementary interventions

Psychosocial and complementary interventions. Various psychosocial interventions (eg, psychoeducation, cognitive behavioral therapy, support groups) have been found to be beneficial in alleviating caregiver symptoms of depression, anxiety, and stress and improving well-being, perceived burden, and quality of life. However, systematic reviews have found variability in the degree of helpfulness of these interventions.^35,36

Some caregivers and care recipients may benefit from complementary and integrative medicine referrals. Mind–body therapies such as mindfulness, yoga, and Tai Chi have shown some beneficial effects.³⁷

Online resources. Caregivers also can be directed to online resources from organizations such as the Alzheimer’s Association (www.alz.org), the National Institutes of Health (www.alzheimers.gov), and the Family Caregiver Alliance (www.caregiver.org).

In rural settings, such as the one in which this case took place, online resources may decrease some barriers to supporting caregivers.³⁸ Internet-based interventions also have been found to have some benefit for dementia caregivers.^31,39

However, some rural locations continue to have limited reliable Internet services.⁴⁰ In affected areas, a strong relationship with a primary care physician may be even more important to the well-being of caregivers, since other support services may be less accessible.⁴¹

Continue to: Impacts of the pandemic

Impacts of the pandemic. Although our case took place prior to the COVID-19 pandemic, it is important to acknowledge ways the pandemic has impacted informal dementia caregiving.

Caregiver stress, depression, and anxiety increased during the pandemic, and the need for greater home confinement and social ­distancing amplified the negative impact of social isolation, including loneliness, on ­caregivers.^42,43 Caregivers often needed to increase their caregiving responsibilities and had more difficulty with care coordination due to limited access to in-person resources.⁴³ The pandemic led to increased reliance on technology and telehealth in the support of dementia caregivers.⁴³

THE CASE

The physician prescribed mirtazapine for Mr. C, titrating the dose as needed to address depressive symptoms and promote weight gain. The physician connected Mr. C’s father with home health services, including physical therapy for fall risk reduction. Mr. C also hired part-time support to provide additional assistance with ADLs and IADLs, allowing Mr. C to have time to attend to his own needs. Though provided with information about a local caregiver support group, Mr. C chose not to attend. The physician also assisted the family with advanced directives.

African American and Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-intensive care, but they tend to use fewer formal support services than White caregivers.

A particular challenge that occurred during care for the family was addressing Mr. C’s father’s driving capacity, considering his strong need for independence. To address this concern, a family meeting was held with Mr. C, his father, and his siblings from out of town. Although Mr. C’s father was not willing to relinquish his driver’s license during that meeting, he agreed to complete a functional driving assessment.

The physician continued to meet with Mr. C and his father together, as well as with Mr. C individually, to provide supportive counseling as needed. As the father’s dementia progressed and it became more difficult to complete office appointments, the physician transitioned to home visits to provide care until the father’s death.

After the death of Mr. C’s father, the physician continued to serve as Mr. C’s primary care provider.

Keeping the “family”in family medicine

Through longitudinal assessment, needs identification, and provision of relevant information, emotional support, and resources, family physicians can provide care that can improve the quality of life and well-being and help alleviate burden experienced by dementia caregivers. Family physicians also are positioned to provide treatments that can address the negative physical and psychological health outcomes associated with informal dementia caregiving. By building relationships with multiple family members across generations, family physicians can understand the context of caregiving dynamics and work together with individuals with dementia and their caregivers throughout disease progression, providing consistent support to the family unit.

CORRESPONDENCE
Kathleen M. Young, PhD, MPH, Novant Health Family Medicine Wilmington, 2523 Delaney Avenue, Wilmington, NC 28403; Kathleen.Young@novanthealth.org

THE CASE

Sam C* is a 68-year-old man who presented to his family physician in a rural health clinic due to concerns about weight loss. Since his visit 8 months prior, Mr. C unintentionally had lost 20 pounds. Upon questioning, Mr. C also reported feeling irritable and having difficulty with sleep and concentration.

A review of systems did not indicate the presence of infection or other medical conditions. In the 6 years since becoming a patient to the practice, he had reported no chronic health concerns, was taking no medications, and had only been to the clinic for his annual check-up appointments. He completed a Patient Health Questionnaire (PHQ-9) and scored 18, indicating moderately severe depression.

Mr. C had established care with his physician when he moved to the area from out of state so that he could be closer to his parents, who were in their mid-80s at the time. Mr. C’s physician also had been the family physician for his parents for the previous 20 years. Three years prior to Mr. C’s presentation for weight loss, his mother had received a diagnosis of acute leukemia; she died a year later.

Over the past year, Mr. C had needed to take a more active role in the care of his father, who was now in his early 90s. Mr. C’s father, who was previously in excellent health, had begun to develop significant health problems, including degenerative arthritis and progressive vascular dementia. He also had ataxia, leading to poor mobility, and a neurogenic bladder requiring self-catheterization, which required Mr. C’s assistance. Mr. C lived next door to his father and provided frequent assistance with activities of daily living. However, his father, who always had been the dominant figure in the family, was determined to maintain his independence and not relinquish control to others.

The strain of caregiving activities, along with managing his father’s inflexibility, was causing increasing distress for Mr. C. As he told his family physician, “I just don’t know what to do.”

● How would you proceed with this patient?

* The patient’s name has been changed to protect his identity.

It is estimated that more than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.¹ As individuals with dementia progressively decline, they require increased assistance with activities of daily living (ADLs, such as bathing and dressing) and instrumental activities of daily living (IADLs, such as paying bills and using transportation). Most of this assistance comes from informal caregiving provided by family members and friends.

Caregiver burden can be defined as “the strain or load borne by a person who cares for a chronically ill, disabled, or elderly family member.”² Caregiver stress has been found to be higher for dementia caregiving than other types of caregiving.³ In particular, caring for someone with greater behavioral and psychological symptoms of dementia (BPSDs) has been associated with higher caregiver burden.^4-7

Beyond the subjective burden of care­giving, there are other potential negative ­consequences for dementia caregivers (see ­TABLE 1^8-14 and TABLE 2^15,16). In addition, caregiver distress is related to a number of care recipient outcomes, including earlier institutionalization, more hospitalizations, more BPSDs, poorer quality of life, and greater likelihood of experiencing elder abuse.¹⁷

Assessment, reassessment are key to meeting needs

Numerous factors can foster caregiver well-­being, including feelings of accomplishment and contribution, a strengthening of the relationship with the care recipient, and feeling supported by friends, family, and formal care systems.^18,19 Family physicians can play an important role by assessing and supporting patients with dementia and their caregivers. Ideally, the individual with dementia and the caregiver will be assessed both together and separately.

Caregiver distress is related to care recipient outcomes, such as earlier institutionalization, more hospitalizations, and poorer quality of life.

A thorough assessment includes gathering information about the context and quality of the caregiving relationship; caregiver perception of the care recipient’s health and functional status; caregiver values and preferences; caregiver well-being (including mental health assessment); caregiver skills, abilities, and knowledge about caregiving; and positive and negative consequences of caregiving.²⁰ Caregiver needs—including informational, care support, emotional, physical, and social needs—also should be assessed.

Continue to: Tools are available...

Tools are available to facilitate caregiver assessment. For example, the Zarit Burden Interview is a 22-item self-report measure that can be given to the caregiver²¹; shorter versions (4 and 12 items) are also available.²² Another resource available for caregiver assessment guidance is a toolkit developed by the Family Caregiver Alliance.²⁰

Continually assess for changing needs

As the condition of the individual with dementia progresses, it will be important to reassess the caregiver, as stressors and needs will change over the course of the caregiving relationship. Support should be adapted ­accordingly.

In the early stage of dementia, caregivers may need information on disease progression and dementia care planning, ways to navigate the health care system, financial planning, and useful resources. Caregivers also may need emotional support to help them adapt to the role of caregiver, deal with denial, and manage their stress.^23,24

With dementia progression, caregivers may need support related to increased decision-making responsibility, managing challenging behaviors, assisting with ADLs and IADLs, and identifying opportunities to meet personal social and well-being needs. They also may need support to accept the changes they are seeing in the individual with dementia and the shifts they are experiencing in their relationship with him or her.^23,25

In late-stage dementia, caregiver needs tend to shift to determining the need for long-term care placement vs staying at home, end-of-life planning, loneliness, and anticipatory grief.^23,26 Support with managing changing and accumulating stress typically remains a primary need throughout the progression of dementia.²⁷

Continue to: Specific populations have distinct needs

Specific populations have distinct needs. Some caregivers, including members of the LGBTQ+ community and different racial and ethnic groups, as well as caregivers of people with younger-onset dementia, may have additional support needs.²⁸

More than 11 million Americans provided more than 18 billion hours in unpaid support for individuals with dementia in 2022, averaging 30 hours of care per caregiver per week.

For example, African American and ­Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-­intensive care, but use fewer formal support services than White caregivers.²⁹ Caregivers from non-White racial and ethnic groups also are more likely to experience discrimination when interacting with health care services on behalf of care recipients.³⁰

Having an awareness of potential specialized needs may help to prevent or address potential care disparities, and cultural humility may help to improve caregiver experiences with primary care physicians.

Resources to support caregivers

Family physicians are well situated to provide informational and emotional support for both patients with dementia and their informal care providers.³¹ Given the variability of caregiver concerns, multicomponent interventions addressing informational, self-care, social support, and financial needs often are needed.³¹ Supportive counseling and psychoeducation can help dementia caregivers with stress management, self-care, coping, and skills training—supporting the development of self-efficacy.^32,33

Outside resources. Although significant caregiver support can be provided directly by the physician, caregivers should be connected with outside resources, including support groups, counselors, psychotherapists, financial and legal support, and formal care services.³⁴

Continue to: Psychosocial and complementary interventions

Psychosocial and complementary interventions. Various psychosocial interventions (eg, psychoeducation, cognitive behavioral therapy, support groups) have been found to be beneficial in alleviating caregiver symptoms of depression, anxiety, and stress and improving well-being, perceived burden, and quality of life. However, systematic reviews have found variability in the degree of helpfulness of these interventions.^35,36

Some caregivers and care recipients may benefit from complementary and integrative medicine referrals. Mind–body therapies such as mindfulness, yoga, and Tai Chi have shown some beneficial effects.³⁷

Online resources. Caregivers also can be directed to online resources from organizations such as the Alzheimer’s Association (www.alz.org), the National Institutes of Health (www.alzheimers.gov), and the Family Caregiver Alliance (www.caregiver.org).

In rural settings, such as the one in which this case took place, online resources may decrease some barriers to supporting caregivers.³⁸ Internet-based interventions also have been found to have some benefit for dementia caregivers.^31,39

However, some rural locations continue to have limited reliable Internet services.⁴⁰ In affected areas, a strong relationship with a primary care physician may be even more important to the well-being of caregivers, since other support services may be less accessible.⁴¹

Continue to: Impacts of the pandemic

Impacts of the pandemic. Although our case took place prior to the COVID-19 pandemic, it is important to acknowledge ways the pandemic has impacted informal dementia caregiving.

Caregiver stress, depression, and anxiety increased during the pandemic, and the need for greater home confinement and social ­distancing amplified the negative impact of social isolation, including loneliness, on ­caregivers.^42,43 Caregivers often needed to increase their caregiving responsibilities and had more difficulty with care coordination due to limited access to in-person resources.⁴³ The pandemic led to increased reliance on technology and telehealth in the support of dementia caregivers.⁴³

THE CASE

The physician prescribed mirtazapine for Mr. C, titrating the dose as needed to address depressive symptoms and promote weight gain. The physician connected Mr. C’s father with home health services, including physical therapy for fall risk reduction. Mr. C also hired part-time support to provide additional assistance with ADLs and IADLs, allowing Mr. C to have time to attend to his own needs. Though provided with information about a local caregiver support group, Mr. C chose not to attend. The physician also assisted the family with advanced directives.

African American and Latino caregivers tend to have caregiving relationships of longer duration, requiring more time-intensive care, but they tend to use fewer formal support services than White caregivers.

A particular challenge that occurred during care for the family was addressing Mr. C’s father’s driving capacity, considering his strong need for independence. To address this concern, a family meeting was held with Mr. C, his father, and his siblings from out of town. Although Mr. C’s father was not willing to relinquish his driver’s license during that meeting, he agreed to complete a functional driving assessment.

The physician continued to meet with Mr. C and his father together, as well as with Mr. C individually, to provide supportive counseling as needed. As the father’s dementia progressed and it became more difficult to complete office appointments, the physician transitioned to home visits to provide care until the father’s death.

After the death of Mr. C’s father, the physician continued to serve as Mr. C’s primary care provider.

Keeping the “family”in family medicine

Through longitudinal assessment, needs identification, and provision of relevant information, emotional support, and resources, family physicians can provide care that can improve the quality of life and well-being and help alleviate burden experienced by dementia caregivers. Family physicians also are positioned to provide treatments that can address the negative physical and psychological health outcomes associated with informal dementia caregiving. By building relationships with multiple family members across generations, family physicians can understand the context of caregiving dynamics and work together with individuals with dementia and their caregivers throughout disease progression, providing consistent support to the family unit.

CORRESPONDENCE
Kathleen M. Young, PhD, MPH, Novant Health Family Medicine Wilmington, 2523 Delaney Avenue, Wilmington, NC 28403; Kathleen.Young@novanthealth.org

Social distancing measures instituted during the ­COVID-19 pandemic challenged the usual way of operating in primary care. To continue delivering medical services, physicians had to transition quickly to forms of remote interaction with patients. Use of technology appeared to be the answer. And it gave clinicians the ability to do what many had long hoped for: offer patients the option of telehealth.

The terms telemedicine and telehealth have similar definitions and are commonly used interchangeably. We think most practices probably would have adopted telehealth earlier were it not for reimbursement barriers. In this article, we adopt the World Health Organization’s definition of telemedicine as: “The delivery of healthcare services, where distance is a critical factor, by all healthcare professionals using information and communication technologies for the exchange of valid information for the diagnosis, treatment, and prevention of disease and injuries, research and evaluation, and for the continuing education of healthcare providers, all in the interests of advancing the health of individuals and their communities.”¹

To provide family medicine clinicians with evidence-based recommendations about telehealth, we conducted a critical review of the literature published through April 30, 2021. The scope of this review includes studies found using the PubMed and Google Scholar databases. In addition, we used the keywords “telehealth,” “telemedicine,” “family medicine,” and “primary care.” We divided this review into 6 sections, including focus areas on implementation in primary care, remote diagnostic accuracy, conditions lending themselves to telehealth, physician and patient perceptions, disparities in telehealth, and finally, the conclusions.

Telehealth implementation in primary care

Telehealth in various forms had been around for years before the pandemic, mainly in the form of commercial telehealth businesses. Telehealth was being used in rural and remote areas where it could be difficult to see a primary care provider—let alone a specialist. The family medicine department of the University of Colorado was an early adopter of telehealth and had navigated this transition since 2017, with clinical champions guiding the process. By 2019, 54% of their clinicians were conducting telehealth encounters.²

However, telehealth implementation elsewhere was not accepted so readily. Before the pandemic, a cross-sectional study of more than 1.1 million patients in Northern California showed that 86% preferred in-­person care over video.³ Even as the pandemic began and social distancing measures were implemented, a quality improvement project at a family medicine residency clinic in Florida documented that clinicians still preferred telephone interviews despite the capacity for video visits.⁴ And many primary care systems were simply unprepared to adopt telehealth technologies.

With time, however, family physicians began to improvise using popular videoconferencing technologies (eg, Zoom) that were readily available and familiar to patients, and medical centers began to repurpose their existing videoconferencing systems.⁵ The Ohio State University Wexner Medical Center launched a virtual health initiative just before the pandemic struck, at which time fewer than 5% of patient visits were conducted through telehealth. Weeks later, nearly 93% of patient visits were offered through telehealth.⁶

Reimbursement. Another significant impediment to early telehealth uptake was the late reaction by the Centers for Medicare and Medicaid Services (CMS) in changing the payment system. Hectic expansion of telehealth in response to the crisis pointed to the lack of policies that supported primary care with payments based on outcomes rather than fee-for-service models.⁷ By the end of April 2020, CMS finally announced that video visits would be reimbursed at the same rate as in-person visits. However, telephone-only visits are still very limited in coverage, and appropriate codes should be verified with payers.

Continue to: Remote diagnosis comes with a caveat

Remote diagnosis comes with a caveat

Some primary care practices have found that images of skin lesions submitted by patients (usually by cell phone) suffice for accurate diagnosis in lieu of office visits.⁸ With chronic conditions, home-based remote monitoring of vital signs may assist in diagnosing and managing acute issues. More efficient triage of patients is increasingly possible with the receipt of still images or video files of concerning lesions (eg, burns, rash, chronic wounds) sent from smartphones alone^9,10 or with devices attached to smartphones (eg, parent-managed otoscopes).^11,12

CMS reimburses for video visits at the same rate it does for in-person visits, but telephone-only visits are still limited in coverage.

Family physicians historically have relied on in-person visits for holistic assessment and diagnosis. Telehealth video visits have the potential to assist with this goal, but there are risks. For example, one patient cut her foot while swimming and the wound became infected. In a video telehealth visit with a physician assistant, the patient was prescribed an oral antibiotic for cellulitis. However, redness and swelling of the wound continued to increase. Subsequent messages left by the patient went unheeded, and she then visited her local emergency department where she received intravenous antibiotics.¹³ Another patient, who had cervical neck discomfort, had a video visit with an urgent care clinic. The initial diagnosis was sciatica; however, the pain continued with the addition of chills, sweats, and subjective fever.¹⁴ Physical examination at the hospital and lab tests revealed endocarditis. These case reports show the limitations of video visits.

Specific conditions usually suitable for telehealth evaluation

The pandemic helped us understand that some situations and conditions are better suited than others to coverage by telehealth. The National Ambulatory Medical Care Survey examined 850 million patient–­physician encounters and found that 66% of all ambulatory primary care visits required in-­office care,¹⁵ suggesting that about one-third of patient encounters could be treated via ­telehealth.

As an example, our southeastern Wisconsin urban clinic has about 20,000 office visits per year. We launched telehealth in March 2020 in direct response to the pandemic. Telehealth usage peaked at the beginning of the pandemic (FIGURE), fell gradually, hit a lower peak in November and December as COVID case counts increased, and then decreased again as our community changed from a “quarantine/lockdown” mentality to “opening up/back to new normal.”

Some conditions can be managed favorably with the telehealth format:

Infectious diseases may be treatable remotely.^16,17 Following an initial telehealth visit, the physician can evaluate and recommend further care.

Stable, chronic conditions. Telehealth can be used for stable, chronic conditions such as diabetes, chronic obstructive pulmonary disease, and heart failure when lab or imaging studies are not needed.¹⁸

Mental health. Telehealth can be useful in counseling and providing mental health and social support.¹⁸ Safeguards can be put in place to protect patient privacy in this setting.¹⁹

Behavioral change. Telehealth can be effective in providing support for patients actively trying to quit smoking or lose weight, and for caregivers. A physician who “checks in” can be a positive motivator and can promote a patient’s continued success.²⁰

Continue to: Telehealth is less beneficial...

Telehealth is less beneficial when a physical exam is needed to assess pain, tenderness, strength, or other sensations. Office visits also are required for lab assays and imaging, as in periodic checks of A1C levels in patients with diabetes. As technology advances, home-based laboratory kits and sensors likely will change this picture. New patients may be better served through an initial office visit to develop the patient–physician relationship.

Visual assessment of conditions may be limited by telehealth depending on the quality of the devices used. For example, rashes may be difficult to assess given the clarity of the picture on the device and the ability to see only in 2D. There is still a need for more controlled trials to clarify which conditions can be evaluated and managed by telehealth and which ones need in-person care.²¹

Physician and patient perceptions of telehealth encounters

Research into family physicians’ perceptions of telehealth is scant. However, 3 studies published in 2021 reveal some advantages and challenges for telehealth adoption.

• A qualitative study found that physicians valued the increased access to care for some patients, changes to reimbursement practices not covered before, and the opportunity to see patients’ home environments.²² Disadvantages included an inability to examine the patient, problems with diagnostic accuracy, hindrances to developing personal connections, and the potential for burnout with on-demand care.²² The researchers suggested that telehealth might better serve to augment in-person care.
• A second study found that clinicians are satisfied with the use of telehealth in general. However, it also noted that the lack of physical examination could hinder accurate diagnosis and treatment.²³
• A third study surveyed 109 family physicians, reinforcing the importance of physical exams and highlighting the lack of body language as another barrier.²⁴

In addition, all 3 studies noted that video visits are typically briefer than in-person visits. Previous research predominantly done in specialty and mental health care showed that the benefits of telehealth for physicians include an increase in efficiency, reduced commute time, and improved work-life balance.²⁵

Patient perspectives. Many patients have reported that they prefer telehealth because of lower costs, decreased travel time, and faster health care access.^26,27 However, patients also have expressed concerns that the telehealth environment may reduce physician attention, can limit personal interaction (and impart a sense of being rushed), and lacks the physical examination that may be key to an adequate diagnosis.²⁸

Continue to: A survey of 223 patients showed...

A survey of 223 patients showed that sicker patients choose in-person care because they want more in-depth visits with more attention to detail than healthier patients do.²⁹ In a Veterans Affairs health care system qualitative study, patients voiced concerns about communicating with physicians via telehealth, including the potential for errors, less attention paid to their needs, audio difficulties, and challenges to establishing a physician–patient relationship.³⁰ Some patients thought telehealth inhibited their personal expression or that the clinician was not attentive enough. These patient reports underscore the importance of patient–clinician relationships developed in person.³¹ The perceived level of complexity involved in a visit appears to be an essential factor in a patient opting for telehealth—or not.

Efficient triage of patients is increasingly possible with still images or videos sent from smartphones.

In light of these known physician and patient perspectives, it seems wise to develop a hybrid model approach in which visits alternate between telehealth and office.

Patient disparities that may limit the use of telehealth

Race and ethnicity is a major factor in telehealth use. Patients who are Black or Hispanic use telehealth services less often than patients who are White.^32,33 A study that looked at patients with chronic conditions—hypertension and diabetes—that disproportionately affect Black and Hispanic patients found that patients in these populations with either of these conditions had a lower prevalence of Internet use when compared with White patients.³⁴ However, subpopulations can vary in their usage. For example, a study in East Harlem, New York, found that Hispanic pregnant women used telehealth frequently for prenatal care and perceived the care as satisfactory.³⁵

Age is also a significant variable in the adoption of telehealth, with pre-­COVID-19 studies finding lower use of technology among older adults. However, a study performed at the University of Missouri during the first months of the pandemic found an increase in telehealth use in seniors,³² although the increase was in telephone use and not full video sessions.

Many patients in need of health care services may have older devices and/or low-speed or no Internet access; they also may lack the technical know-how to conduct a telehealth visit.^4,36 For example, regardless of race or ethnicity, patients on government insurance (Medicaid and Medicare) have been shown to complete more telephone than video visits,³⁷ underscoring the importance of telehealth practice flexibility and the need for increased technology support to decrease the digital divide. Even with adequate technological support and patient training, telehealth may be more complicated if patients have such comorbidities as hearing, visual, or cognitive impairment.³¹ Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.³⁸

Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.

Overall, incorporating telehealth for the care of older and/or vulnerable patients will present a unique set of challenges that organizations must address. Efforts must be made to understand the available technologies and patients’ comfort in using them. A hybrid model offering telehealth and in-office encounters may be the best solution.

CORRESPONDENCE
Hernan Barenboim, PhD, KPC Health Group, 301 North San Jacinto Street, Hemet, CA 92543; hbarenboim@gmail.com

Social distancing measures instituted during the ­COVID-19 pandemic challenged the usual way of operating in primary care. To continue delivering medical services, physicians had to transition quickly to forms of remote interaction with patients. Use of technology appeared to be the answer. And it gave clinicians the ability to do what many had long hoped for: offer patients the option of telehealth.

The terms telemedicine and telehealth have similar definitions and are commonly used interchangeably. We think most practices probably would have adopted telehealth earlier were it not for reimbursement barriers. In this article, we adopt the World Health Organization’s definition of telemedicine as: “The delivery of healthcare services, where distance is a critical factor, by all healthcare professionals using information and communication technologies for the exchange of valid information for the diagnosis, treatment, and prevention of disease and injuries, research and evaluation, and for the continuing education of healthcare providers, all in the interests of advancing the health of individuals and their communities.”¹

To provide family medicine clinicians with evidence-based recommendations about telehealth, we conducted a critical review of the literature published through April 30, 2021. The scope of this review includes studies found using the PubMed and Google Scholar databases. In addition, we used the keywords “telehealth,” “telemedicine,” “family medicine,” and “primary care.” We divided this review into 6 sections, including focus areas on implementation in primary care, remote diagnostic accuracy, conditions lending themselves to telehealth, physician and patient perceptions, disparities in telehealth, and finally, the conclusions.

Telehealth implementation in primary care

Telehealth in various forms had been around for years before the pandemic, mainly in the form of commercial telehealth businesses. Telehealth was being used in rural and remote areas where it could be difficult to see a primary care provider—let alone a specialist. The family medicine department of the University of Colorado was an early adopter of telehealth and had navigated this transition since 2017, with clinical champions guiding the process. By 2019, 54% of their clinicians were conducting telehealth encounters.²

However, telehealth implementation elsewhere was not accepted so readily. Before the pandemic, a cross-sectional study of more than 1.1 million patients in Northern California showed that 86% preferred in-­person care over video.³ Even as the pandemic began and social distancing measures were implemented, a quality improvement project at a family medicine residency clinic in Florida documented that clinicians still preferred telephone interviews despite the capacity for video visits.⁴ And many primary care systems were simply unprepared to adopt telehealth technologies.

With time, however, family physicians began to improvise using popular videoconferencing technologies (eg, Zoom) that were readily available and familiar to patients, and medical centers began to repurpose their existing videoconferencing systems.⁵ The Ohio State University Wexner Medical Center launched a virtual health initiative just before the pandemic struck, at which time fewer than 5% of patient visits were conducted through telehealth. Weeks later, nearly 93% of patient visits were offered through telehealth.⁶

Reimbursement. Another significant impediment to early telehealth uptake was the late reaction by the Centers for Medicare and Medicaid Services (CMS) in changing the payment system. Hectic expansion of telehealth in response to the crisis pointed to the lack of policies that supported primary care with payments based on outcomes rather than fee-for-service models.⁷ By the end of April 2020, CMS finally announced that video visits would be reimbursed at the same rate as in-person visits. However, telephone-only visits are still very limited in coverage, and appropriate codes should be verified with payers.

Continue to: Remote diagnosis comes with a caveat

Remote diagnosis comes with a caveat

Some primary care practices have found that images of skin lesions submitted by patients (usually by cell phone) suffice for accurate diagnosis in lieu of office visits.⁸ With chronic conditions, home-based remote monitoring of vital signs may assist in diagnosing and managing acute issues. More efficient triage of patients is increasingly possible with the receipt of still images or video files of concerning lesions (eg, burns, rash, chronic wounds) sent from smartphones alone^9,10 or with devices attached to smartphones (eg, parent-managed otoscopes).^11,12

CMS reimburses for video visits at the same rate it does for in-person visits, but telephone-only visits are still limited in coverage.

Family physicians historically have relied on in-person visits for holistic assessment and diagnosis. Telehealth video visits have the potential to assist with this goal, but there are risks. For example, one patient cut her foot while swimming and the wound became infected. In a video telehealth visit with a physician assistant, the patient was prescribed an oral antibiotic for cellulitis. However, redness and swelling of the wound continued to increase. Subsequent messages left by the patient went unheeded, and she then visited her local emergency department where she received intravenous antibiotics.¹³ Another patient, who had cervical neck discomfort, had a video visit with an urgent care clinic. The initial diagnosis was sciatica; however, the pain continued with the addition of chills, sweats, and subjective fever.¹⁴ Physical examination at the hospital and lab tests revealed endocarditis. These case reports show the limitations of video visits.

Specific conditions usually suitable for telehealth evaluation

The pandemic helped us understand that some situations and conditions are better suited than others to coverage by telehealth. The National Ambulatory Medical Care Survey examined 850 million patient–­physician encounters and found that 66% of all ambulatory primary care visits required in-­office care,¹⁵ suggesting that about one-third of patient encounters could be treated via ­telehealth.

As an example, our southeastern Wisconsin urban clinic has about 20,000 office visits per year. We launched telehealth in March 2020 in direct response to the pandemic. Telehealth usage peaked at the beginning of the pandemic (FIGURE), fell gradually, hit a lower peak in November and December as COVID case counts increased, and then decreased again as our community changed from a “quarantine/lockdown” mentality to “opening up/back to new normal.”

Some conditions can be managed favorably with the telehealth format:

Infectious diseases may be treatable remotely.^16,17 Following an initial telehealth visit, the physician can evaluate and recommend further care.

Stable, chronic conditions. Telehealth can be used for stable, chronic conditions such as diabetes, chronic obstructive pulmonary disease, and heart failure when lab or imaging studies are not needed.¹⁸

Mental health. Telehealth can be useful in counseling and providing mental health and social support.¹⁸ Safeguards can be put in place to protect patient privacy in this setting.¹⁹

Behavioral change. Telehealth can be effective in providing support for patients actively trying to quit smoking or lose weight, and for caregivers. A physician who “checks in” can be a positive motivator and can promote a patient’s continued success.²⁰

Continue to: Telehealth is less beneficial...

Telehealth is less beneficial when a physical exam is needed to assess pain, tenderness, strength, or other sensations. Office visits also are required for lab assays and imaging, as in periodic checks of A1C levels in patients with diabetes. As technology advances, home-based laboratory kits and sensors likely will change this picture. New patients may be better served through an initial office visit to develop the patient–physician relationship.

Visual assessment of conditions may be limited by telehealth depending on the quality of the devices used. For example, rashes may be difficult to assess given the clarity of the picture on the device and the ability to see only in 2D. There is still a need for more controlled trials to clarify which conditions can be evaluated and managed by telehealth and which ones need in-person care.²¹

Physician and patient perceptions of telehealth encounters

Research into family physicians’ perceptions of telehealth is scant. However, 3 studies published in 2021 reveal some advantages and challenges for telehealth adoption.

• A qualitative study found that physicians valued the increased access to care for some patients, changes to reimbursement practices not covered before, and the opportunity to see patients’ home environments.²² Disadvantages included an inability to examine the patient, problems with diagnostic accuracy, hindrances to developing personal connections, and the potential for burnout with on-demand care.²² The researchers suggested that telehealth might better serve to augment in-person care.
• A second study found that clinicians are satisfied with the use of telehealth in general. However, it also noted that the lack of physical examination could hinder accurate diagnosis and treatment.²³
• A third study surveyed 109 family physicians, reinforcing the importance of physical exams and highlighting the lack of body language as another barrier.²⁴

In addition, all 3 studies noted that video visits are typically briefer than in-person visits. Previous research predominantly done in specialty and mental health care showed that the benefits of telehealth for physicians include an increase in efficiency, reduced commute time, and improved work-life balance.²⁵

Patient perspectives. Many patients have reported that they prefer telehealth because of lower costs, decreased travel time, and faster health care access.^26,27 However, patients also have expressed concerns that the telehealth environment may reduce physician attention, can limit personal interaction (and impart a sense of being rushed), and lacks the physical examination that may be key to an adequate diagnosis.²⁸

Continue to: A survey of 223 patients showed...

A survey of 223 patients showed that sicker patients choose in-person care because they want more in-depth visits with more attention to detail than healthier patients do.²⁹ In a Veterans Affairs health care system qualitative study, patients voiced concerns about communicating with physicians via telehealth, including the potential for errors, less attention paid to their needs, audio difficulties, and challenges to establishing a physician–patient relationship.³⁰ Some patients thought telehealth inhibited their personal expression or that the clinician was not attentive enough. These patient reports underscore the importance of patient–clinician relationships developed in person.³¹ The perceived level of complexity involved in a visit appears to be an essential factor in a patient opting for telehealth—or not.

Efficient triage of patients is increasingly possible with still images or videos sent from smartphones.

In light of these known physician and patient perspectives, it seems wise to develop a hybrid model approach in which visits alternate between telehealth and office.

Patient disparities that may limit the use of telehealth

Race and ethnicity is a major factor in telehealth use. Patients who are Black or Hispanic use telehealth services less often than patients who are White.^32,33 A study that looked at patients with chronic conditions—hypertension and diabetes—that disproportionately affect Black and Hispanic patients found that patients in these populations with either of these conditions had a lower prevalence of Internet use when compared with White patients.³⁴ However, subpopulations can vary in their usage. For example, a study in East Harlem, New York, found that Hispanic pregnant women used telehealth frequently for prenatal care and perceived the care as satisfactory.³⁵

Age is also a significant variable in the adoption of telehealth, with pre-­COVID-19 studies finding lower use of technology among older adults. However, a study performed at the University of Missouri during the first months of the pandemic found an increase in telehealth use in seniors,³² although the increase was in telephone use and not full video sessions.

Many patients in need of health care services may have older devices and/or low-speed or no Internet access; they also may lack the technical know-how to conduct a telehealth visit.^4,36 For example, regardless of race or ethnicity, patients on government insurance (Medicaid and Medicare) have been shown to complete more telephone than video visits,³⁷ underscoring the importance of telehealth practice flexibility and the need for increased technology support to decrease the digital divide. Even with adequate technological support and patient training, telehealth may be more complicated if patients have such comorbidities as hearing, visual, or cognitive impairment.³¹ Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.³⁸

Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.

Overall, incorporating telehealth for the care of older and/or vulnerable patients will present a unique set of challenges that organizations must address. Efforts must be made to understand the available technologies and patients’ comfort in using them. A hybrid model offering telehealth and in-office encounters may be the best solution.

CORRESPONDENCE
Hernan Barenboim, PhD, KPC Health Group, 301 North San Jacinto Street, Hemet, CA 92543; hbarenboim@gmail.com

Social distancing measures instituted during the ­COVID-19 pandemic challenged the usual way of operating in primary care. To continue delivering medical services, physicians had to transition quickly to forms of remote interaction with patients. Use of technology appeared to be the answer. And it gave clinicians the ability to do what many had long hoped for: offer patients the option of telehealth.

The terms telemedicine and telehealth have similar definitions and are commonly used interchangeably. We think most practices probably would have adopted telehealth earlier were it not for reimbursement barriers. In this article, we adopt the World Health Organization’s definition of telemedicine as: “The delivery of healthcare services, where distance is a critical factor, by all healthcare professionals using information and communication technologies for the exchange of valid information for the diagnosis, treatment, and prevention of disease and injuries, research and evaluation, and for the continuing education of healthcare providers, all in the interests of advancing the health of individuals and their communities.”¹

To provide family medicine clinicians with evidence-based recommendations about telehealth, we conducted a critical review of the literature published through April 30, 2021. The scope of this review includes studies found using the PubMed and Google Scholar databases. In addition, we used the keywords “telehealth,” “telemedicine,” “family medicine,” and “primary care.” We divided this review into 6 sections, including focus areas on implementation in primary care, remote diagnostic accuracy, conditions lending themselves to telehealth, physician and patient perceptions, disparities in telehealth, and finally, the conclusions.

Telehealth implementation in primary care

Telehealth in various forms had been around for years before the pandemic, mainly in the form of commercial telehealth businesses. Telehealth was being used in rural and remote areas where it could be difficult to see a primary care provider—let alone a specialist. The family medicine department of the University of Colorado was an early adopter of telehealth and had navigated this transition since 2017, with clinical champions guiding the process. By 2019, 54% of their clinicians were conducting telehealth encounters.²

However, telehealth implementation elsewhere was not accepted so readily. Before the pandemic, a cross-sectional study of more than 1.1 million patients in Northern California showed that 86% preferred in-­person care over video.³ Even as the pandemic began and social distancing measures were implemented, a quality improvement project at a family medicine residency clinic in Florida documented that clinicians still preferred telephone interviews despite the capacity for video visits.⁴ And many primary care systems were simply unprepared to adopt telehealth technologies.

With time, however, family physicians began to improvise using popular videoconferencing technologies (eg, Zoom) that were readily available and familiar to patients, and medical centers began to repurpose their existing videoconferencing systems.⁵ The Ohio State University Wexner Medical Center launched a virtual health initiative just before the pandemic struck, at which time fewer than 5% of patient visits were conducted through telehealth. Weeks later, nearly 93% of patient visits were offered through telehealth.⁶

Reimbursement. Another significant impediment to early telehealth uptake was the late reaction by the Centers for Medicare and Medicaid Services (CMS) in changing the payment system. Hectic expansion of telehealth in response to the crisis pointed to the lack of policies that supported primary care with payments based on outcomes rather than fee-for-service models.⁷ By the end of April 2020, CMS finally announced that video visits would be reimbursed at the same rate as in-person visits. However, telephone-only visits are still very limited in coverage, and appropriate codes should be verified with payers.

Continue to: Remote diagnosis comes with a caveat

Remote diagnosis comes with a caveat

Some primary care practices have found that images of skin lesions submitted by patients (usually by cell phone) suffice for accurate diagnosis in lieu of office visits.⁸ With chronic conditions, home-based remote monitoring of vital signs may assist in diagnosing and managing acute issues. More efficient triage of patients is increasingly possible with the receipt of still images or video files of concerning lesions (eg, burns, rash, chronic wounds) sent from smartphones alone^9,10 or with devices attached to smartphones (eg, parent-managed otoscopes).^11,12

CMS reimburses for video visits at the same rate it does for in-person visits, but telephone-only visits are still limited in coverage.

Family physicians historically have relied on in-person visits for holistic assessment and diagnosis. Telehealth video visits have the potential to assist with this goal, but there are risks. For example, one patient cut her foot while swimming and the wound became infected. In a video telehealth visit with a physician assistant, the patient was prescribed an oral antibiotic for cellulitis. However, redness and swelling of the wound continued to increase. Subsequent messages left by the patient went unheeded, and she then visited her local emergency department where she received intravenous antibiotics.¹³ Another patient, who had cervical neck discomfort, had a video visit with an urgent care clinic. The initial diagnosis was sciatica; however, the pain continued with the addition of chills, sweats, and subjective fever.¹⁴ Physical examination at the hospital and lab tests revealed endocarditis. These case reports show the limitations of video visits.

Specific conditions usually suitable for telehealth evaluation

The pandemic helped us understand that some situations and conditions are better suited than others to coverage by telehealth. The National Ambulatory Medical Care Survey examined 850 million patient–­physician encounters and found that 66% of all ambulatory primary care visits required in-­office care,¹⁵ suggesting that about one-third of patient encounters could be treated via ­telehealth.

As an example, our southeastern Wisconsin urban clinic has about 20,000 office visits per year. We launched telehealth in March 2020 in direct response to the pandemic. Telehealth usage peaked at the beginning of the pandemic (FIGURE), fell gradually, hit a lower peak in November and December as COVID case counts increased, and then decreased again as our community changed from a “quarantine/lockdown” mentality to “opening up/back to new normal.”

Some conditions can be managed favorably with the telehealth format:

Infectious diseases may be treatable remotely.^16,17 Following an initial telehealth visit, the physician can evaluate and recommend further care.

Stable, chronic conditions. Telehealth can be used for stable, chronic conditions such as diabetes, chronic obstructive pulmonary disease, and heart failure when lab or imaging studies are not needed.¹⁸

Mental health. Telehealth can be useful in counseling and providing mental health and social support.¹⁸ Safeguards can be put in place to protect patient privacy in this setting.¹⁹

Behavioral change. Telehealth can be effective in providing support for patients actively trying to quit smoking or lose weight, and for caregivers. A physician who “checks in” can be a positive motivator and can promote a patient’s continued success.²⁰

Continue to: Telehealth is less beneficial...

Telehealth is less beneficial when a physical exam is needed to assess pain, tenderness, strength, or other sensations. Office visits also are required for lab assays and imaging, as in periodic checks of A1C levels in patients with diabetes. As technology advances, home-based laboratory kits and sensors likely will change this picture. New patients may be better served through an initial office visit to develop the patient–physician relationship.

Visual assessment of conditions may be limited by telehealth depending on the quality of the devices used. For example, rashes may be difficult to assess given the clarity of the picture on the device and the ability to see only in 2D. There is still a need for more controlled trials to clarify which conditions can be evaluated and managed by telehealth and which ones need in-person care.²¹

Physician and patient perceptions of telehealth encounters

Research into family physicians’ perceptions of telehealth is scant. However, 3 studies published in 2021 reveal some advantages and challenges for telehealth adoption.

• A qualitative study found that physicians valued the increased access to care for some patients, changes to reimbursement practices not covered before, and the opportunity to see patients’ home environments.²² Disadvantages included an inability to examine the patient, problems with diagnostic accuracy, hindrances to developing personal connections, and the potential for burnout with on-demand care.²² The researchers suggested that telehealth might better serve to augment in-person care.
• A second study found that clinicians are satisfied with the use of telehealth in general. However, it also noted that the lack of physical examination could hinder accurate diagnosis and treatment.²³
• A third study surveyed 109 family physicians, reinforcing the importance of physical exams and highlighting the lack of body language as another barrier.²⁴

In addition, all 3 studies noted that video visits are typically briefer than in-person visits. Previous research predominantly done in specialty and mental health care showed that the benefits of telehealth for physicians include an increase in efficiency, reduced commute time, and improved work-life balance.²⁵

Patient perspectives. Many patients have reported that they prefer telehealth because of lower costs, decreased travel time, and faster health care access.^26,27 However, patients also have expressed concerns that the telehealth environment may reduce physician attention, can limit personal interaction (and impart a sense of being rushed), and lacks the physical examination that may be key to an adequate diagnosis.²⁸

Continue to: A survey of 223 patients showed...

A survey of 223 patients showed that sicker patients choose in-person care because they want more in-depth visits with more attention to detail than healthier patients do.²⁹ In a Veterans Affairs health care system qualitative study, patients voiced concerns about communicating with physicians via telehealth, including the potential for errors, less attention paid to their needs, audio difficulties, and challenges to establishing a physician–patient relationship.³⁰ Some patients thought telehealth inhibited their personal expression or that the clinician was not attentive enough. These patient reports underscore the importance of patient–clinician relationships developed in person.³¹ The perceived level of complexity involved in a visit appears to be an essential factor in a patient opting for telehealth—or not.

Efficient triage of patients is increasingly possible with still images or videos sent from smartphones.

In light of these known physician and patient perspectives, it seems wise to develop a hybrid model approach in which visits alternate between telehealth and office.

Patient disparities that may limit the use of telehealth

Race and ethnicity is a major factor in telehealth use. Patients who are Black or Hispanic use telehealth services less often than patients who are White.^32,33 A study that looked at patients with chronic conditions—hypertension and diabetes—that disproportionately affect Black and Hispanic patients found that patients in these populations with either of these conditions had a lower prevalence of Internet use when compared with White patients.³⁴ However, subpopulations can vary in their usage. For example, a study in East Harlem, New York, found that Hispanic pregnant women used telehealth frequently for prenatal care and perceived the care as satisfactory.³⁵

Age is also a significant variable in the adoption of telehealth, with pre-­COVID-19 studies finding lower use of technology among older adults. However, a study performed at the University of Missouri during the first months of the pandemic found an increase in telehealth use in seniors,³² although the increase was in telephone use and not full video sessions.

Many patients in need of health care services may have older devices and/or low-speed or no Internet access; they also may lack the technical know-how to conduct a telehealth visit.^4,36 For example, regardless of race or ethnicity, patients on government insurance (Medicaid and Medicare) have been shown to complete more telephone than video visits,³⁷ underscoring the importance of telehealth practice flexibility and the need for increased technology support to decrease the digital divide. Even with adequate technological support and patient training, telehealth may be more complicated if patients have such comorbidities as hearing, visual, or cognitive impairment.³¹ Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.³⁸

Patients from a lower socioeconomic status may feel uncomfortable with providers seeing their home environment on video.

Overall, incorporating telehealth for the care of older and/or vulnerable patients will present a unique set of challenges that organizations must address. Efforts must be made to understand the available technologies and patients’ comfort in using them. A hybrid model offering telehealth and in-office encounters may be the best solution.

CORRESPONDENCE
Hernan Barenboim, PhD, KPC Health Group, 301 North San Jacinto Street, Hemet, CA 92543; hbarenboim@gmail.com

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸ The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

 

 

Lifestyle modifications: As important as medication

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; jarrett8@uic.edu

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸ The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

 

 

Lifestyle modifications: As important as medication

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; jarrett8@uic.edu

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸ The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

 

 

Lifestyle modifications: As important as medication

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; jarrett8@uic.edu

Platelet-rich plasma (PRP) injections have become a popular treatment option in a variety of specialties including sports medicine, maxillofacial surgery, dermatology, cosmetology, and reproductive medicine.¹ PRP is an autologous blood product derived from whole blood, using a centrifuge to isolate a concentrated layer of platelets. The ­a-granules in platelets release transforming growth factor b 1, vascular endothelial growth factor, platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor 1, and other mediators that enhance the natural healing process.²

When patients ask. Familiarity with the use of PRP to treat specific musculoskeletal (MSK) conditions is essential for family physicians who frequently are asked by patients about whether PRP is right for them. These patients may have experienced failure of medication therapy or declined surgical intervention, or may not be surgical candidates. This review details the evidence surrounding common intra-articular and extra-articular applications of PRP. But first, a word about how PRP is prepared, its contraindications, and costs.

Preparation and types of PRP

Although there are many commercial systems for preparing PRP, there is no consensus on the optimal formulation.² Other terms for PRP, such as autologous concentrated platelets and super-concentrated platelets, are based on concentration of red blood cells, leukocytes, and fibrin.³ PRP therapies usually are categorized as leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), based on neutrophil concentrations that are above and below baseline.² Leukocyte concentration is one of the most debated topics in PRP therapy.⁴

Common commercially available preparation systems produce platelet concentrations between 3 to 6 times the baseline platelet count.⁵ Although there is no universally agreed upon PRP formulation, studies have shown 2 centrifugation cycles (“double-spun” or “dual centrifugation”) that yield platelet concentrations between 1.8 to 1.9 times the baseline values significantly improve MSK conditions.^6-8

Familiarity with the use of platelet-rich plasma to treat specific musculoskeletal conditions is essential for FPs who frequently are asked by patients about whether it is right for them.

For MSK purposes, PRP may be injected into intratendinous, peritendinous, and intra-articular spaces. Currently, there is no consensus regarding injection frequency. Many studies have incorporated single-­injection protocols, while some have used 2 to 3 injections repeated over several weeks to months. PRP commonly is injected at point-of-care without requiring storage.

Contraindications. PRP has been shown to be safe, with most adverse effects attributed to local injection site pain, bleeding, swelling, and bruising.⁹

Contraindications to PRP include active malignancy or recent remission from malignancy with the exception of nonmetastatic skin tumors.¹⁰ PRP is not recommended for patients with an allergy to manufacturing components (eg, dimethyl sulfoxide), thrombocytopenia, nonsteroidal anti-­inflammatory drug use within 2 weeks, active infection causing fever, and local infection at the injection site.¹⁰ Since local anesthetics may impair platelet function, they should not be given at the same injection site as PRP.¹⁰

Continue to: Cost

Cost. PRP is not covered by most insurance plans.^11,12 The cost for PRP may range from $500 to $2500 for a single injection.¹²

Evidence-based summary by condition

Knee osteoarthritis

❯❯❯ Consider using PRP

Knee osteoarthritis (OA) is a common cause of pain and disability. Treatment options include physical therapy, pharmacotherapy, and surgery. PRP has gained popularity as a nonsurgical option. A recent meta-analysis by Costa et al¹³ of 40 studies with 3035 participants comparing intra-articular PRP with hyaluronic acid (HA), corticosteroid, and saline injections, found that PRP appears to be more effective or as effective as other nonsurgical modalities. However, due to study heterogeneity and high risk for bias, the authors could not recommend PRP for knee OA in clinical practice.¹³

Despite Costa et al’s findings, reproducible data have demonstrated the superiority of PRP over other nonsurgical treatment options for knee OA. A 2021 systematic review and meta-analysis of 18 randomized controlled trials (RCTs; N = 811) by Belk et al⁶ comparing PRP to HA injections showed a higher mean improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in the PRP group compared to the HA group (44.7% vs 12.6%, respectively; P < .01).⁶ Six of 11 studies using the visual analog scale (VAS) for pain reported significantly less pain in the PRP group compared to the HA group (P < .05).⁶ The mean follow-up time was 11.1 months.⁶ Three of 6 studies reported improved subjective International Knee Documentation Committee (IKDC) scores (range from 0-100, with higher scores representing higher levels of function and lower levels of symptoms) in the PRP group compared to the HA group: 75.7 ± 15.1 vs 65.6 ± 16.9 (P = .004); 65.5 ± 3.6 vs 55.8 ± 3.8 (P = .01); and 60.8 ± 9.8 vs 48.4 ± 6.2 (P < .05).⁶ There was concern for moderate-to-high heterogeneity.⁶

PRP has been shown to be safe, with most adverse effects attributed to local injectionsite pain, bleeding, swelling, and bruising.

Other systematic reviews and meta-­analyses found similar efficacy of PRP for knee OA, including improved WOMAC scores and patient-reported outcomes (eg, pain, physical function, stiffness) compared to other injectable options.^14,15 A systematic review of 14 RCTs (N = 1423) by Shen et al¹⁵ showed improved WOMAC scores at 3 months (mean differences [MD] = –14.53; 95% CI, –29.97 to –7.09; P < .001), 6 months (MD = –18.21; 95% CI, –27.84 to –8.95; P < .001), and 12 months (MD = –19.45; 95% CI, –26.90 to –12.82; P < .001) in favor of PRP vs controls (saline placebo, ozone, corticosteroids, HA).¹⁵

Despite a lack of consensus regarding the optimal preparation of PRP for knee OA, another recent RCT (N = 192) found significant improvement in mean subjective IKDC scores in the LR-PRP group (45.5 ± 15.5 to 60.7 ± 21.1; P < .0005) and the LP-PRP group (46.8 ± 15.8 to 62.9 ± 19.9; P < .0005), indicating efficacy regardless of PRP type.⁴

Continue to: Ankle osteoarthritis

 

 

Ankle osteoarthritis

❯ ❯ ❯   Additional research is needed

Ankle OA affects 3.4% of all adults and is more common in the younger population than knee or hip OA.¹⁶ An RCT (N = 100) investigating PRP vs placebo (saline) injections showed no statistically significant difference in American Orthopedic Foot and Ankle Society scores evaluating pain and function over 26 weeks (–2 points; 95% CI, –5 to 1; P = .16).¹⁶ Limitations to this study include its small sample size and the PRP formulation used. (The intervention group received 2 injections of 2 mL of PRP, and the platelet concentration was not reported.)¹⁶

A 2020 systematic review and meta-­analysis of 4 RCTs and 5 case series by Evans et al¹⁷ concluded that PRP improves pain and function in small-joint OA compared to controls of saline, corticosteroids, and HA.¹⁷ One of the case series (N = 20) included in the study demonstrated improvement in ankle OA pain and function scores at 24 weeks posttreatment (P = .04), although improvement in pain and function peaked at 12 weeks.¹⁷ In addition, a 2017 retrospective study (N = 20) from the review reported improved VAS scores and function at 17 months following 4 injections of PRP over 4 weeks (P < .001).¹⁷ Given that RCT data found no benefit with PRP in treating small-joint OA, additional research is indicated.

Hip osteoarthritis

❯ ❯ ❯   Additional research is needed

Symptomatic hip OA occurs in 40% of adults older than 65 years, with a higher prevalence in women.¹⁸ Currently, corticosteroid injections are the only intra-articular therapy recommended by international guidelines for hip OA.¹⁹ A systematic review and meta-analysis comparing PRP to HA injections that included 4 RCTs (N = 303) showed a statistically significant reduction in VAS scores at 2 months in the PRP group compared to the HA group (weighted mean difference [WMD] = –0.376; 95% CI, –0.614 to –0.138; P = .002).¹⁸ However, there were no significant differences in VAS scores between the PRP and HA groups at 6 months (WMD = –0.141; 95% CI, –0.401 to 0.119; P = .289) and 12 months (WMD = –0.083; 95% CI, –0.343 to 0.117; P = .534). Likewise, no significant differences were found in WOMAC scores at 6 months (WMD = –2.841; 95% CI, –6.248 to 0.565; P = .102) and 12 months (WMD = –3.134; 95% CI, –6.624 to 0.356; P = .078) and Harris Hip Scores (HHS) at 6 months (WMD = 2.782; 95% CI, –6.639 to 12.203; P =.563) and 12 months (WMD = 0.706; 95% CI, –6.333 to 7.745; P = .844).¹⁸

A systematic review of 6 RCTs (N = 408) by Belk et al²⁰ comparing PRP to HA for hip OA found similar short-term improvements in WOMAC scores (standardized mean differences [SMD] = 0.27; 95% CI, –0.05 to 0.59; P = .09), VAS scores (MD = 0.59; 95% CI, –0.741 to 1.92; P = .39), and HHS (MD = -0.81; 95% CI, –10.06 to 8.43; P = .93). The average follow-up time was 12.2 and 11.9 months for the PRP and HA groups, respectively.²⁰

LR-PRP, which was used in 1 of the 6 RCTs, showed improvement in VAS scores and HHS from baseline, but no significant difference compared to HA at the latest follow-­up.²⁰ A pooled subanalysis of the 3 studies that used LP-PRP found no difference in WOMAC scores between the PRP and HA groups (SMD = 0.42; 95% CI, –0.01 to 0.86; P = .06).²⁰ Future studies comparing the efficacy of intra-articular steroid vs PRP for hip OA would be beneficial.¹⁸

Continue to: Rotator cuff tendinopathy

Rotator cuff tendinopathy

❯ ❯ ❯   Consider PRP for short-term pain relief

Painful conditions of the rotator cuff include impingement syndrome, tendonitis, and partial and complete tears. A 2021 RCT (N = 58) by Dadgostar et al²¹ comparing PRP injection to corticosteroid therapy (methylprednisolone and lidocaine) for the treatment of rotator cuff tendinopathy showed significant improvement in VAS scores at 3 months in the PRP group compared to the corticosteroid group (6.66 ± 2.26 to 3.08 ± 2.14 vs 5.53 ± 1.80 to 3.88 ± 1.99, respectively; P = .023). There also were more significant improvements in adduction in the PRP group compared to the corticosteroid group (20.50° ± 8.23° to 28° ± 3.61° vs 23.21° ± 7.09° to 28.46° ± 4.18°, respectively; P = .011), and external rotation (59.66° ± 23.81° to 76.66° ± 18.30° vs 57.14°± 24.69° to 65.57° ± 26.39° for the PRP and corticosteroid groups, respectively; P = .036).²¹

Another RCT (N = 99) by Kwong et al²² comparing PRP to corticosteroids found similar short-term advantages of LP-PRP with an improved VAS score (–13.6 vs 0.4; P = .03), American Shoulder and Elbow Surgeons score (13.0 vs 2.9; P = .02), and Western Ontario Rotator Cuff Index score (16.8 vs 5.8; P = .03). However, there was no long-term benefit of PRP over corticosteroids found at 12 months.²²

A 2021 systematic review and meta-­analysis by Hamid et al²³ that included 8 RCTs (N = 976) favored PRP over control (no injection, saline injections, and/or shoulder rehabilitation) with improved VAS scores at 12 months (SMD = –0.5; 95% CI, –0.7 to –0.2; P < .001). The evidence on functional outcome was mixed. Data pooled from 2 studies (n = 228) found better Shoulder Pain and Disability Index (SPADI) scores compared to controls at 3- and 6-month follow-ups. However, there were no significant differences in Disabilities of the Arm, Shoulder and Hand (DASH) scores between the 2 groups.²³

Patellar tendinopathy

❯ ❯ ❯   Consider using PRP for return to sport

Patellar tendinopathy, a common MSK condition encountered in the primary care setting, has an overall prevalence of 22% in elite athletes at some point in their career.^{24 ­}Nonsurgical management options include rest, ice, eccentric and isometric exercises, anti-­inflammatory drugs, extracorporeal shock wave therapy (ESWT), and dry needling (DN).

Currently, corticosteroid injections are the only intraarticular therapy recommended by international guidelines for hip OA.

A 2014 RCT (N = 23) evaluating DN vs PRP for patellar tendinopathy favored PRP with improved VAS scores (mean ± SD = 25.4 ± 23.2 points; P = .01 vs 5.2 ± 12.5 points; P = .20) at 12 weeks (P = .02). However, at ≥ 26 weeks, the improvement in pain and function scores was similar between the DN and PRP groups (33.2 ± 14.0 points; P = .001 vs 28.9 ± 25.2 points; P = .01). Notably, there was significantly more improvement in the PRP group at 12 weeks (P = .02) but not at 26 weeks (P = .66).²⁵

Continue to: Another perspective study...

Another prospective study (N = 31) comparing PRP to physiotherapy showed a greater improvement in sport activity level reflected by the Tegner score in the PRP group (percentage improvement, 39 ± 22%) compared to control (20 ± 27%; P = .048) at 6 months.⁷

A recent RCT (N = 20) revealed improved VAS scores at 6 months with rehabilitation paired with either bone marrow mesenchymal stem cells (BM-MSC) or LP-PRP when compared with baseline (BM-MSC group: 4.23 ± 2.13 to 2.52 ± 2.37; P = .0621; LP-PRP group: 3.10 ± 1.20 to 1.13 ± 1.25; P = .0083). Pain was significantly reduced during sport play in both groups at 6 months when compared with baseline (BM-MSC group: 6.91 ± 1.11 to 3.06 ± 2.89, P = .0049; PRP group: 7.03 ± 1.42 to 1.94 ± 1.24, P = .0001).²⁶

A 2019 systematic review and meta-analysis (N = 2530) demonstrated greater improvements in Victorian Institute of Sport Assessment scale for patellar tendinopathy (VISA-P) with multiple injections of PRP (38.7 points; 95% CI, 26.3-51.2 points) compared to single injections of PRP (24.3 points; 95% CI, 18.2-30.5 points), eccentric exercise (28.3 points; 95% CI, 18.9-37.8 points) and ESWT (27.4 points; 95% CI, 10.0-39.8 points) after 6 months.²⁷ In contrast, an RCT (n = 57) comparing a single injection of LR-PRP or LP-PRP was no more effective than a single injection of saline for improvement in mean VISA-P scores (P > .05) at 1 year.²⁸

Lateral epicondylitis

❯ ❯ ❯   Consider using PRP

Lateral epicondylitis (“tennis elbow”) is caused by overuse of the elbow extensors at the site of the lateral epicondyle. Chronic lateral epicondylosis involves tissue degeneration and microtrauma. Most cases of epicondylar tendinopathies are treated nonoperatively, with corticosteroid injections being a mainstay of treatment despite their short-term benefit²⁹ and potential to deteriorate connective tissue over time. Recent studies suggest PRP therapy for epicondylitis and epicondylosis may increase long-term pain relief and improve function.

The evidence on functional outcome of platelet-rich plasma for rotator cuff tendinopathy is mixed.

A 2017 systematic review and meta-­analysis of 16 RCTs (N = 1018) concluded PRP was more efficacious than control injections (bupivacaine) for pain reduction in tendinopathies (effect size = 0.47; 95% CI, 0.22-0.72).³⁰ In the review, lateral epicondylitis was evaluated in 12 studies and was most responsive to PRP (effect size = 0.57) when compared to control injection.³⁰ In another systematic review (5 RCTs; 250 patients), corticosteroid injections improved pain within the first 6 weeks of treatment. However, PRP outperformed corticosteroid in VAS scores (21.3 ± 28.1 vs 42.4 ± 26.8) and DASH scores (17.6 ± 24.0 vs 36.5 ± 23.8) (P < .001) at 2 years.³¹

Continue to: A 2022 systematic review...

A 2022 systematic review and meta-­analysis (26 studies; N = 1040) comparing scores at baseline vs 2 years post-PRP showed improvement in VAS scores (7.4 ± 1.30 vs 3.71 ± 2.35; P < .001), DASH scores (60.8 ± 12.5 vs 13.0 ± 18.5; P < .001), Patient-Rated Tennis Elbow Evaluation (55.6 ± 14.7 vs 48.8 ± 4.1; P < .001), and Mayo Clinic Performance Index (55.5 ± 6.1 vs 93.0 ± 6.7; P < .001).³²

Regarding the therapeutic effects of different PRP types in lateral epicondylitis, a 2022 systematic review of 33 studies (N = 2420) found improved function and pain relief with LR-PRP and LP-PRP with no significant differences.³³ Pretreatment VAS scores in the LR-PRP group, which ranged from 6.1 to 8.0, improved to 1.5 to 4.0 at 3 months and 0.6 to 3.3 after 1 year.³³ Similarly, pretreatment VAS scores in the LP-PRP group, which ranged from 4.2 to 8.4, improved to 1.6 to 5.9 at 3 months and 0.7 to 2.7 after 1 year.³⁴ DASH scores also improved in the LR-PRP and LP-PRP groups, with pretreatment scores (LR-PRP, 47.0 to 54.3; LP-PRP, 30.0 to 67.7) improving to 20.0 to 22.0 and 5.5 to 19.0, respectively, at 1 year.³³

Achilles tendinopathy

❯ ❯ ❯   Do not use PRP; evidence is lacking

Achilles tendinopathy, caused by chronic overuse and overload resulting in microtrauma and poor tissue healing, typically occurs in the most poorly vascularized portion of the tendon and is common in runners. First-line treatments for Achilles tendinopathy include eccentric strength training and anti-­inflammatory drugs.^34,35 Corticosteroid injections are not recommended, given concern for degraded tendon tissue over time and worse function.³⁴

A 2020 systematic review of 11 randomized and nonrandomized clinical trials (N = 406) found PRP improved Victorian Institute of Sports Assessment—Achilles (VISA-A) scores at 24 weeks compared to other nonsurgical treatment options (41.2 vs 70.12; P < .018).³⁴ However, a higher-quality 2021 systematic review and meta-analysis of 4 RCTs (N = 170) comparing PRP injections with placebo showed no significant difference in VISA-A scores at 3 months (0.23; 95% CI, –0.45 to 0.91), 6 months (0.83; 95% CI, –0.26 to 1.92), and 12 months (0.83; 95% CI, –0.77 to 2.44).³⁶ Therefore, further studies are warranted to evaluate the benefit of PRP injections for Achilles tendinopathy.

Conclusions

While high-quality studies support the use of PRP for knee OA and lateral epicondylitis, they have a moderate-to-high risk for bias. Several RCTs show that PRP provides superior short-term pain relief and range of motion compared to corticosteroids for rotator cuff tendinopathy. Multiple injections of PRP for patellar tendinopathy may accelerate return to sport and improve symptoms over the long term. However, current evidence does not support PRP therapy for Achilles tendinopathy. Given variability in PRP preparation, an accurate interpretation of the literature regarding its use in MSK conditions is recommended (TABLE^{4,6,7,14-18,20-23,25-28,30-34,36}).

Continue to: Concerning the effectiveness of PRP...

Concerning the effectiveness of PRP, it is important to consider early publication bias. Although recent studies have shown its benefits,^6,14,15,37 additional studies comparing PRP to placebo will help demonstrate its efficacy. Interestingly, a literature search by Bar-Or et al³⁸ found intra-articular saline may have a therapeutic effect on knee OA and confound findings when used as a placebo.

RCT data showed no benefit with platelet-rich plasma in treating small-joint osteoarthritis.

Recognizing the presence or lack of clinically significant improvement in the literature is important. For example, while some recent studies have shown PRP exceeds the minimal clinically significant difference for knee OA and lateral epicondylitis, others have not.^32,37 A 2021 systematic review of 11 clinical practice guidelines for the use of PRP in knee OA found that 9 were “uncertain or unable to make a recommendation” and 2 recommended against it.³⁹

In its 2021 position statement for the responsible use of regenerative medicine, the American Medical Society for Sports Medicine includes guidance on integrating orthobiologics into clinical practice. The guideline emphasizes informed consent and provides an evidence-based rationale for using PRP in certain patient populations (lateral epicondylitis and younger patients with mild-to-­moderate knee OA), recommending its use only after exhausting other conservative options.⁴⁰ Patients should be referred to physicians with experience using PRP and image-guided procedures.

CORRESPONDENCE
Gregory D. Bentz Jr, MD, 3640 High Street Suite 3B, Portsmouth, VA 23707; bentzgd@evms.edu

Platelet-rich plasma (PRP) injections have become a popular treatment option in a variety of specialties including sports medicine, maxillofacial surgery, dermatology, cosmetology, and reproductive medicine.¹ PRP is an autologous blood product derived from whole blood, using a centrifuge to isolate a concentrated layer of platelets. The ­a-granules in platelets release transforming growth factor b 1, vascular endothelial growth factor, platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor 1, and other mediators that enhance the natural healing process.²

When patients ask. Familiarity with the use of PRP to treat specific musculoskeletal (MSK) conditions is essential for family physicians who frequently are asked by patients about whether PRP is right for them. These patients may have experienced failure of medication therapy or declined surgical intervention, or may not be surgical candidates. This review details the evidence surrounding common intra-articular and extra-articular applications of PRP. But first, a word about how PRP is prepared, its contraindications, and costs.

Preparation and types of PRP

Although there are many commercial systems for preparing PRP, there is no consensus on the optimal formulation.² Other terms for PRP, such as autologous concentrated platelets and super-concentrated platelets, are based on concentration of red blood cells, leukocytes, and fibrin.³ PRP therapies usually are categorized as leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), based on neutrophil concentrations that are above and below baseline.² Leukocyte concentration is one of the most debated topics in PRP therapy.⁴

Common commercially available preparation systems produce platelet concentrations between 3 to 6 times the baseline platelet count.⁵ Although there is no universally agreed upon PRP formulation, studies have shown 2 centrifugation cycles (“double-spun” or “dual centrifugation”) that yield platelet concentrations between 1.8 to 1.9 times the baseline values significantly improve MSK conditions.^6-8

Familiarity with the use of platelet-rich plasma to treat specific musculoskeletal conditions is essential for FPs who frequently are asked by patients about whether it is right for them.

For MSK purposes, PRP may be injected into intratendinous, peritendinous, and intra-articular spaces. Currently, there is no consensus regarding injection frequency. Many studies have incorporated single-­injection protocols, while some have used 2 to 3 injections repeated over several weeks to months. PRP commonly is injected at point-of-care without requiring storage.

Contraindications. PRP has been shown to be safe, with most adverse effects attributed to local injection site pain, bleeding, swelling, and bruising.⁹

Contraindications to PRP include active malignancy or recent remission from malignancy with the exception of nonmetastatic skin tumors.¹⁰ PRP is not recommended for patients with an allergy to manufacturing components (eg, dimethyl sulfoxide), thrombocytopenia, nonsteroidal anti-­inflammatory drug use within 2 weeks, active infection causing fever, and local infection at the injection site.¹⁰ Since local anesthetics may impair platelet function, they should not be given at the same injection site as PRP.¹⁰

Continue to: Cost

Cost. PRP is not covered by most insurance plans.^11,12 The cost for PRP may range from $500 to $2500 for a single injection.¹²

Evidence-based summary by condition

Knee osteoarthritis

❯❯❯ Consider using PRP

Knee osteoarthritis (OA) is a common cause of pain and disability. Treatment options include physical therapy, pharmacotherapy, and surgery. PRP has gained popularity as a nonsurgical option. A recent meta-analysis by Costa et al¹³ of 40 studies with 3035 participants comparing intra-articular PRP with hyaluronic acid (HA), corticosteroid, and saline injections, found that PRP appears to be more effective or as effective as other nonsurgical modalities. However, due to study heterogeneity and high risk for bias, the authors could not recommend PRP for knee OA in clinical practice.¹³

Despite Costa et al’s findings, reproducible data have demonstrated the superiority of PRP over other nonsurgical treatment options for knee OA. A 2021 systematic review and meta-analysis of 18 randomized controlled trials (RCTs; N = 811) by Belk et al⁶ comparing PRP to HA injections showed a higher mean improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in the PRP group compared to the HA group (44.7% vs 12.6%, respectively; P < .01).⁶ Six of 11 studies using the visual analog scale (VAS) for pain reported significantly less pain in the PRP group compared to the HA group (P < .05).⁶ The mean follow-up time was 11.1 months.⁶ Three of 6 studies reported improved subjective International Knee Documentation Committee (IKDC) scores (range from 0-100, with higher scores representing higher levels of function and lower levels of symptoms) in the PRP group compared to the HA group: 75.7 ± 15.1 vs 65.6 ± 16.9 (P = .004); 65.5 ± 3.6 vs 55.8 ± 3.8 (P = .01); and 60.8 ± 9.8 vs 48.4 ± 6.2 (P < .05).⁶ There was concern for moderate-to-high heterogeneity.⁶

PRP has been shown to be safe, with most adverse effects attributed to local injectionsite pain, bleeding, swelling, and bruising.

Other systematic reviews and meta-­analyses found similar efficacy of PRP for knee OA, including improved WOMAC scores and patient-reported outcomes (eg, pain, physical function, stiffness) compared to other injectable options.^14,15 A systematic review of 14 RCTs (N = 1423) by Shen et al¹⁵ showed improved WOMAC scores at 3 months (mean differences [MD] = –14.53; 95% CI, –29.97 to –7.09; P < .001), 6 months (MD = –18.21; 95% CI, –27.84 to –8.95; P < .001), and 12 months (MD = –19.45; 95% CI, –26.90 to –12.82; P < .001) in favor of PRP vs controls (saline placebo, ozone, corticosteroids, HA).¹⁵

Despite a lack of consensus regarding the optimal preparation of PRP for knee OA, another recent RCT (N = 192) found significant improvement in mean subjective IKDC scores in the LR-PRP group (45.5 ± 15.5 to 60.7 ± 21.1; P < .0005) and the LP-PRP group (46.8 ± 15.8 to 62.9 ± 19.9; P < .0005), indicating efficacy regardless of PRP type.⁴

Continue to: Ankle osteoarthritis

 

 

Ankle osteoarthritis

❯ ❯ ❯   Additional research is needed

Ankle OA affects 3.4% of all adults and is more common in the younger population than knee or hip OA.¹⁶ An RCT (N = 100) investigating PRP vs placebo (saline) injections showed no statistically significant difference in American Orthopedic Foot and Ankle Society scores evaluating pain and function over 26 weeks (–2 points; 95% CI, –5 to 1; P = .16).¹⁶ Limitations to this study include its small sample size and the PRP formulation used. (The intervention group received 2 injections of 2 mL of PRP, and the platelet concentration was not reported.)¹⁶

A 2020 systematic review and meta-­analysis of 4 RCTs and 5 case series by Evans et al¹⁷ concluded that PRP improves pain and function in small-joint OA compared to controls of saline, corticosteroids, and HA.¹⁷ One of the case series (N = 20) included in the study demonstrated improvement in ankle OA pain and function scores at 24 weeks posttreatment (P = .04), although improvement in pain and function peaked at 12 weeks.¹⁷ In addition, a 2017 retrospective study (N = 20) from the review reported improved VAS scores and function at 17 months following 4 injections of PRP over 4 weeks (P < .001).¹⁷ Given that RCT data found no benefit with PRP in treating small-joint OA, additional research is indicated.

Hip osteoarthritis

❯ ❯ ❯   Additional research is needed

Symptomatic hip OA occurs in 40% of adults older than 65 years, with a higher prevalence in women.¹⁸ Currently, corticosteroid injections are the only intra-articular therapy recommended by international guidelines for hip OA.¹⁹ A systematic review and meta-analysis comparing PRP to HA injections that included 4 RCTs (N = 303) showed a statistically significant reduction in VAS scores at 2 months in the PRP group compared to the HA group (weighted mean difference [WMD] = –0.376; 95% CI, –0.614 to –0.138; P = .002).¹⁸ However, there were no significant differences in VAS scores between the PRP and HA groups at 6 months (WMD = –0.141; 95% CI, –0.401 to 0.119; P = .289) and 12 months (WMD = –0.083; 95% CI, –0.343 to 0.117; P = .534). Likewise, no significant differences were found in WOMAC scores at 6 months (WMD = –2.841; 95% CI, –6.248 to 0.565; P = .102) and 12 months (WMD = –3.134; 95% CI, –6.624 to 0.356; P = .078) and Harris Hip Scores (HHS) at 6 months (WMD = 2.782; 95% CI, –6.639 to 12.203; P =.563) and 12 months (WMD = 0.706; 95% CI, –6.333 to 7.745; P = .844).¹⁸

A systematic review of 6 RCTs (N = 408) by Belk et al²⁰ comparing PRP to HA for hip OA found similar short-term improvements in WOMAC scores (standardized mean differences [SMD] = 0.27; 95% CI, –0.05 to 0.59; P = .09), VAS scores (MD = 0.59; 95% CI, –0.741 to 1.92; P = .39), and HHS (MD = -0.81; 95% CI, –10.06 to 8.43; P = .93). The average follow-up time was 12.2 and 11.9 months for the PRP and HA groups, respectively.²⁰

LR-PRP, which was used in 1 of the 6 RCTs, showed improvement in VAS scores and HHS from baseline, but no significant difference compared to HA at the latest follow-­up.²⁰ A pooled subanalysis of the 3 studies that used LP-PRP found no difference in WOMAC scores between the PRP and HA groups (SMD = 0.42; 95% CI, –0.01 to 0.86; P = .06).²⁰ Future studies comparing the efficacy of intra-articular steroid vs PRP for hip OA would be beneficial.¹⁸

Continue to: Rotator cuff tendinopathy

Rotator cuff tendinopathy

❯ ❯ ❯   Consider PRP for short-term pain relief

Painful conditions of the rotator cuff include impingement syndrome, tendonitis, and partial and complete tears. A 2021 RCT (N = 58) by Dadgostar et al²¹ comparing PRP injection to corticosteroid therapy (methylprednisolone and lidocaine) for the treatment of rotator cuff tendinopathy showed significant improvement in VAS scores at 3 months in the PRP group compared to the corticosteroid group (6.66 ± 2.26 to 3.08 ± 2.14 vs 5.53 ± 1.80 to 3.88 ± 1.99, respectively; P = .023). There also were more significant improvements in adduction in the PRP group compared to the corticosteroid group (20.50° ± 8.23° to 28° ± 3.61° vs 23.21° ± 7.09° to 28.46° ± 4.18°, respectively; P = .011), and external rotation (59.66° ± 23.81° to 76.66° ± 18.30° vs 57.14°± 24.69° to 65.57° ± 26.39° for the PRP and corticosteroid groups, respectively; P = .036).²¹

Another RCT (N = 99) by Kwong et al²² comparing PRP to corticosteroids found similar short-term advantages of LP-PRP with an improved VAS score (–13.6 vs 0.4; P = .03), American Shoulder and Elbow Surgeons score (13.0 vs 2.9; P = .02), and Western Ontario Rotator Cuff Index score (16.8 vs 5.8; P = .03). However, there was no long-term benefit of PRP over corticosteroids found at 12 months.²²

A 2021 systematic review and meta-­analysis by Hamid et al²³ that included 8 RCTs (N = 976) favored PRP over control (no injection, saline injections, and/or shoulder rehabilitation) with improved VAS scores at 12 months (SMD = –0.5; 95% CI, –0.7 to –0.2; P < .001). The evidence on functional outcome was mixed. Data pooled from 2 studies (n = 228) found better Shoulder Pain and Disability Index (SPADI) scores compared to controls at 3- and 6-month follow-ups. However, there were no significant differences in Disabilities of the Arm, Shoulder and Hand (DASH) scores between the 2 groups.²³

Patellar tendinopathy

❯ ❯ ❯   Consider using PRP for return to sport

Patellar tendinopathy, a common MSK condition encountered in the primary care setting, has an overall prevalence of 22% in elite athletes at some point in their career.^{24 ­}Nonsurgical management options include rest, ice, eccentric and isometric exercises, anti-­inflammatory drugs, extracorporeal shock wave therapy (ESWT), and dry needling (DN).

Currently, corticosteroid injections are the only intraarticular therapy recommended by international guidelines for hip OA.

A 2014 RCT (N = 23) evaluating DN vs PRP for patellar tendinopathy favored PRP with improved VAS scores (mean ± SD = 25.4 ± 23.2 points; P = .01 vs 5.2 ± 12.5 points; P = .20) at 12 weeks (P = .02). However, at ≥ 26 weeks, the improvement in pain and function scores was similar between the DN and PRP groups (33.2 ± 14.0 points; P = .001 vs 28.9 ± 25.2 points; P = .01). Notably, there was significantly more improvement in the PRP group at 12 weeks (P = .02) but not at 26 weeks (P = .66).²⁵

Continue to: Another perspective study...

Another prospective study (N = 31) comparing PRP to physiotherapy showed a greater improvement in sport activity level reflected by the Tegner score in the PRP group (percentage improvement, 39 ± 22%) compared to control (20 ± 27%; P = .048) at 6 months.⁷

A recent RCT (N = 20) revealed improved VAS scores at 6 months with rehabilitation paired with either bone marrow mesenchymal stem cells (BM-MSC) or LP-PRP when compared with baseline (BM-MSC group: 4.23 ± 2.13 to 2.52 ± 2.37; P = .0621; LP-PRP group: 3.10 ± 1.20 to 1.13 ± 1.25; P = .0083). Pain was significantly reduced during sport play in both groups at 6 months when compared with baseline (BM-MSC group: 6.91 ± 1.11 to 3.06 ± 2.89, P = .0049; PRP group: 7.03 ± 1.42 to 1.94 ± 1.24, P = .0001).²⁶

A 2019 systematic review and meta-analysis (N = 2530) demonstrated greater improvements in Victorian Institute of Sport Assessment scale for patellar tendinopathy (VISA-P) with multiple injections of PRP (38.7 points; 95% CI, 26.3-51.2 points) compared to single injections of PRP (24.3 points; 95% CI, 18.2-30.5 points), eccentric exercise (28.3 points; 95% CI, 18.9-37.8 points) and ESWT (27.4 points; 95% CI, 10.0-39.8 points) after 6 months.²⁷ In contrast, an RCT (n = 57) comparing a single injection of LR-PRP or LP-PRP was no more effective than a single injection of saline for improvement in mean VISA-P scores (P > .05) at 1 year.²⁸

Lateral epicondylitis

❯ ❯ ❯   Consider using PRP

Lateral epicondylitis (“tennis elbow”) is caused by overuse of the elbow extensors at the site of the lateral epicondyle. Chronic lateral epicondylosis involves tissue degeneration and microtrauma. Most cases of epicondylar tendinopathies are treated nonoperatively, with corticosteroid injections being a mainstay of treatment despite their short-term benefit²⁹ and potential to deteriorate connective tissue over time. Recent studies suggest PRP therapy for epicondylitis and epicondylosis may increase long-term pain relief and improve function.

The evidence on functional outcome of platelet-rich plasma for rotator cuff tendinopathy is mixed.

A 2017 systematic review and meta-­analysis of 16 RCTs (N = 1018) concluded PRP was more efficacious than control injections (bupivacaine) for pain reduction in tendinopathies (effect size = 0.47; 95% CI, 0.22-0.72).³⁰ In the review, lateral epicondylitis was evaluated in 12 studies and was most responsive to PRP (effect size = 0.57) when compared to control injection.³⁰ In another systematic review (5 RCTs; 250 patients), corticosteroid injections improved pain within the first 6 weeks of treatment. However, PRP outperformed corticosteroid in VAS scores (21.3 ± 28.1 vs 42.4 ± 26.8) and DASH scores (17.6 ± 24.0 vs 36.5 ± 23.8) (P < .001) at 2 years.³¹

Continue to: A 2022 systematic review...

A 2022 systematic review and meta-­analysis (26 studies; N = 1040) comparing scores at baseline vs 2 years post-PRP showed improvement in VAS scores (7.4 ± 1.30 vs 3.71 ± 2.35; P < .001), DASH scores (60.8 ± 12.5 vs 13.0 ± 18.5; P < .001), Patient-Rated Tennis Elbow Evaluation (55.6 ± 14.7 vs 48.8 ± 4.1; P < .001), and Mayo Clinic Performance Index (55.5 ± 6.1 vs 93.0 ± 6.7; P < .001).³²

Regarding the therapeutic effects of different PRP types in lateral epicondylitis, a 2022 systematic review of 33 studies (N = 2420) found improved function and pain relief with LR-PRP and LP-PRP with no significant differences.³³ Pretreatment VAS scores in the LR-PRP group, which ranged from 6.1 to 8.0, improved to 1.5 to 4.0 at 3 months and 0.6 to 3.3 after 1 year.³³ Similarly, pretreatment VAS scores in the LP-PRP group, which ranged from 4.2 to 8.4, improved to 1.6 to 5.9 at 3 months and 0.7 to 2.7 after 1 year.³⁴ DASH scores also improved in the LR-PRP and LP-PRP groups, with pretreatment scores (LR-PRP, 47.0 to 54.3; LP-PRP, 30.0 to 67.7) improving to 20.0 to 22.0 and 5.5 to 19.0, respectively, at 1 year.³³

Achilles tendinopathy

❯ ❯ ❯   Do not use PRP; evidence is lacking

Achilles tendinopathy, caused by chronic overuse and overload resulting in microtrauma and poor tissue healing, typically occurs in the most poorly vascularized portion of the tendon and is common in runners. First-line treatments for Achilles tendinopathy include eccentric strength training and anti-­inflammatory drugs.^34,35 Corticosteroid injections are not recommended, given concern for degraded tendon tissue over time and worse function.³⁴

A 2020 systematic review of 11 randomized and nonrandomized clinical trials (N = 406) found PRP improved Victorian Institute of Sports Assessment—Achilles (VISA-A) scores at 24 weeks compared to other nonsurgical treatment options (41.2 vs 70.12; P < .018).³⁴ However, a higher-quality 2021 systematic review and meta-analysis of 4 RCTs (N = 170) comparing PRP injections with placebo showed no significant difference in VISA-A scores at 3 months (0.23; 95% CI, –0.45 to 0.91), 6 months (0.83; 95% CI, –0.26 to 1.92), and 12 months (0.83; 95% CI, –0.77 to 2.44).³⁶ Therefore, further studies are warranted to evaluate the benefit of PRP injections for Achilles tendinopathy.

Conclusions

While high-quality studies support the use of PRP for knee OA and lateral epicondylitis, they have a moderate-to-high risk for bias. Several RCTs show that PRP provides superior short-term pain relief and range of motion compared to corticosteroids for rotator cuff tendinopathy. Multiple injections of PRP for patellar tendinopathy may accelerate return to sport and improve symptoms over the long term. However, current evidence does not support PRP therapy for Achilles tendinopathy. Given variability in PRP preparation, an accurate interpretation of the literature regarding its use in MSK conditions is recommended (TABLE^{4,6,7,14-18,20-23,25-28,30-34,36}).

Continue to: Concerning the effectiveness of PRP...

Concerning the effectiveness of PRP, it is important to consider early publication bias. Although recent studies have shown its benefits,^6,14,15,37 additional studies comparing PRP to placebo will help demonstrate its efficacy. Interestingly, a literature search by Bar-Or et al³⁸ found intra-articular saline may have a therapeutic effect on knee OA and confound findings when used as a placebo.

RCT data showed no benefit with platelet-rich plasma in treating small-joint osteoarthritis.

Recognizing the presence or lack of clinically significant improvement in the literature is important. For example, while some recent studies have shown PRP exceeds the minimal clinically significant difference for knee OA and lateral epicondylitis, others have not.^32,37 A 2021 systematic review of 11 clinical practice guidelines for the use of PRP in knee OA found that 9 were “uncertain or unable to make a recommendation” and 2 recommended against it.³⁹

In its 2021 position statement for the responsible use of regenerative medicine, the American Medical Society for Sports Medicine includes guidance on integrating orthobiologics into clinical practice. The guideline emphasizes informed consent and provides an evidence-based rationale for using PRP in certain patient populations (lateral epicondylitis and younger patients with mild-to-­moderate knee OA), recommending its use only after exhausting other conservative options.⁴⁰ Patients should be referred to physicians with experience using PRP and image-guided procedures.

CORRESPONDENCE
Gregory D. Bentz Jr, MD, 3640 High Street Suite 3B, Portsmouth, VA 23707; bentzgd@evms.edu

Platelet-rich plasma (PRP) injections have become a popular treatment option in a variety of specialties including sports medicine, maxillofacial surgery, dermatology, cosmetology, and reproductive medicine.¹ PRP is an autologous blood product derived from whole blood, using a centrifuge to isolate a concentrated layer of platelets. The ­a-granules in platelets release transforming growth factor b 1, vascular endothelial growth factor, platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor 1, and other mediators that enhance the natural healing process.²

When patients ask. Familiarity with the use of PRP to treat specific musculoskeletal (MSK) conditions is essential for family physicians who frequently are asked by patients about whether PRP is right for them. These patients may have experienced failure of medication therapy or declined surgical intervention, or may not be surgical candidates. This review details the evidence surrounding common intra-articular and extra-articular applications of PRP. But first, a word about how PRP is prepared, its contraindications, and costs.

Preparation and types of PRP

Although there are many commercial systems for preparing PRP, there is no consensus on the optimal formulation.² Other terms for PRP, such as autologous concentrated platelets and super-concentrated platelets, are based on concentration of red blood cells, leukocytes, and fibrin.³ PRP therapies usually are categorized as leukocyte-rich PRP (LR-PRP) or leukocyte-poor PRP (LP-PRP), based on neutrophil concentrations that are above and below baseline.² Leukocyte concentration is one of the most debated topics in PRP therapy.⁴

Common commercially available preparation systems produce platelet concentrations between 3 to 6 times the baseline platelet count.⁵ Although there is no universally agreed upon PRP formulation, studies have shown 2 centrifugation cycles (“double-spun” or “dual centrifugation”) that yield platelet concentrations between 1.8 to 1.9 times the baseline values significantly improve MSK conditions.^6-8

Familiarity with the use of platelet-rich plasma to treat specific musculoskeletal conditions is essential for FPs who frequently are asked by patients about whether it is right for them.

For MSK purposes, PRP may be injected into intratendinous, peritendinous, and intra-articular spaces. Currently, there is no consensus regarding injection frequency. Many studies have incorporated single-­injection protocols, while some have used 2 to 3 injections repeated over several weeks to months. PRP commonly is injected at point-of-care without requiring storage.

Contraindications. PRP has been shown to be safe, with most adverse effects attributed to local injection site pain, bleeding, swelling, and bruising.⁹

Contraindications to PRP include active malignancy or recent remission from malignancy with the exception of nonmetastatic skin tumors.¹⁰ PRP is not recommended for patients with an allergy to manufacturing components (eg, dimethyl sulfoxide), thrombocytopenia, nonsteroidal anti-­inflammatory drug use within 2 weeks, active infection causing fever, and local infection at the injection site.¹⁰ Since local anesthetics may impair platelet function, they should not be given at the same injection site as PRP.¹⁰

Continue to: Cost

Cost. PRP is not covered by most insurance plans.^11,12 The cost for PRP may range from $500 to $2500 for a single injection.¹²

Evidence-based summary by condition

Knee osteoarthritis

❯❯❯ Consider using PRP

Knee osteoarthritis (OA) is a common cause of pain and disability. Treatment options include physical therapy, pharmacotherapy, and surgery. PRP has gained popularity as a nonsurgical option. A recent meta-analysis by Costa et al¹³ of 40 studies with 3035 participants comparing intra-articular PRP with hyaluronic acid (HA), corticosteroid, and saline injections, found that PRP appears to be more effective or as effective as other nonsurgical modalities. However, due to study heterogeneity and high risk for bias, the authors could not recommend PRP for knee OA in clinical practice.¹³

Despite Costa et al’s findings, reproducible data have demonstrated the superiority of PRP over other nonsurgical treatment options for knee OA. A 2021 systematic review and meta-analysis of 18 randomized controlled trials (RCTs; N = 811) by Belk et al⁶ comparing PRP to HA injections showed a higher mean improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in the PRP group compared to the HA group (44.7% vs 12.6%, respectively; P < .01).⁶ Six of 11 studies using the visual analog scale (VAS) for pain reported significantly less pain in the PRP group compared to the HA group (P < .05).⁶ The mean follow-up time was 11.1 months.⁶ Three of 6 studies reported improved subjective International Knee Documentation Committee (IKDC) scores (range from 0-100, with higher scores representing higher levels of function and lower levels of symptoms) in the PRP group compared to the HA group: 75.7 ± 15.1 vs 65.6 ± 16.9 (P = .004); 65.5 ± 3.6 vs 55.8 ± 3.8 (P = .01); and 60.8 ± 9.8 vs 48.4 ± 6.2 (P < .05).⁶ There was concern for moderate-to-high heterogeneity.⁶

PRP has been shown to be safe, with most adverse effects attributed to local injectionsite pain, bleeding, swelling, and bruising.

Other systematic reviews and meta-­analyses found similar efficacy of PRP for knee OA, including improved WOMAC scores and patient-reported outcomes (eg, pain, physical function, stiffness) compared to other injectable options.^14,15 A systematic review of 14 RCTs (N = 1423) by Shen et al¹⁵ showed improved WOMAC scores at 3 months (mean differences [MD] = –14.53; 95% CI, –29.97 to –7.09; P < .001), 6 months (MD = –18.21; 95% CI, –27.84 to –8.95; P < .001), and 12 months (MD = –19.45; 95% CI, –26.90 to –12.82; P < .001) in favor of PRP vs controls (saline placebo, ozone, corticosteroids, HA).¹⁵

Despite a lack of consensus regarding the optimal preparation of PRP for knee OA, another recent RCT (N = 192) found significant improvement in mean subjective IKDC scores in the LR-PRP group (45.5 ± 15.5 to 60.7 ± 21.1; P < .0005) and the LP-PRP group (46.8 ± 15.8 to 62.9 ± 19.9; P < .0005), indicating efficacy regardless of PRP type.⁴

Continue to: Ankle osteoarthritis

 

 

Ankle osteoarthritis

❯ ❯ ❯   Additional research is needed

Ankle OA affects 3.4% of all adults and is more common in the younger population than knee or hip OA.¹⁶ An RCT (N = 100) investigating PRP vs placebo (saline) injections showed no statistically significant difference in American Orthopedic Foot and Ankle Society scores evaluating pain and function over 26 weeks (–2 points; 95% CI, –5 to 1; P = .16).¹⁶ Limitations to this study include its small sample size and the PRP formulation used. (The intervention group received 2 injections of 2 mL of PRP, and the platelet concentration was not reported.)¹⁶

A 2020 systematic review and meta-­analysis of 4 RCTs and 5 case series by Evans et al¹⁷ concluded that PRP improves pain and function in small-joint OA compared to controls of saline, corticosteroids, and HA.¹⁷ One of the case series (N = 20) included in the study demonstrated improvement in ankle OA pain and function scores at 24 weeks posttreatment (P = .04), although improvement in pain and function peaked at 12 weeks.¹⁷ In addition, a 2017 retrospective study (N = 20) from the review reported improved VAS scores and function at 17 months following 4 injections of PRP over 4 weeks (P < .001).¹⁷ Given that RCT data found no benefit with PRP in treating small-joint OA, additional research is indicated.

Hip osteoarthritis

❯ ❯ ❯   Additional research is needed

Symptomatic hip OA occurs in 40% of adults older than 65 years, with a higher prevalence in women.¹⁸ Currently, corticosteroid injections are the only intra-articular therapy recommended by international guidelines for hip OA.¹⁹ A systematic review and meta-analysis comparing PRP to HA injections that included 4 RCTs (N = 303) showed a statistically significant reduction in VAS scores at 2 months in the PRP group compared to the HA group (weighted mean difference [WMD] = –0.376; 95% CI, –0.614 to –0.138; P = .002).¹⁸ However, there were no significant differences in VAS scores between the PRP and HA groups at 6 months (WMD = –0.141; 95% CI, –0.401 to 0.119; P = .289) and 12 months (WMD = –0.083; 95% CI, –0.343 to 0.117; P = .534). Likewise, no significant differences were found in WOMAC scores at 6 months (WMD = –2.841; 95% CI, –6.248 to 0.565; P = .102) and 12 months (WMD = –3.134; 95% CI, –6.624 to 0.356; P = .078) and Harris Hip Scores (HHS) at 6 months (WMD = 2.782; 95% CI, –6.639 to 12.203; P =.563) and 12 months (WMD = 0.706; 95% CI, –6.333 to 7.745; P = .844).¹⁸

A systematic review of 6 RCTs (N = 408) by Belk et al²⁰ comparing PRP to HA for hip OA found similar short-term improvements in WOMAC scores (standardized mean differences [SMD] = 0.27; 95% CI, –0.05 to 0.59; P = .09), VAS scores (MD = 0.59; 95% CI, –0.741 to 1.92; P = .39), and HHS (MD = -0.81; 95% CI, –10.06 to 8.43; P = .93). The average follow-up time was 12.2 and 11.9 months for the PRP and HA groups, respectively.²⁰

LR-PRP, which was used in 1 of the 6 RCTs, showed improvement in VAS scores and HHS from baseline, but no significant difference compared to HA at the latest follow-­up.²⁰ A pooled subanalysis of the 3 studies that used LP-PRP found no difference in WOMAC scores between the PRP and HA groups (SMD = 0.42; 95% CI, –0.01 to 0.86; P = .06).²⁰ Future studies comparing the efficacy of intra-articular steroid vs PRP for hip OA would be beneficial.¹⁸

Continue to: Rotator cuff tendinopathy

Rotator cuff tendinopathy

❯ ❯ ❯   Consider PRP for short-term pain relief

Painful conditions of the rotator cuff include impingement syndrome, tendonitis, and partial and complete tears. A 2021 RCT (N = 58) by Dadgostar et al²¹ comparing PRP injection to corticosteroid therapy (methylprednisolone and lidocaine) for the treatment of rotator cuff tendinopathy showed significant improvement in VAS scores at 3 months in the PRP group compared to the corticosteroid group (6.66 ± 2.26 to 3.08 ± 2.14 vs 5.53 ± 1.80 to 3.88 ± 1.99, respectively; P = .023). There also were more significant improvements in adduction in the PRP group compared to the corticosteroid group (20.50° ± 8.23° to 28° ± 3.61° vs 23.21° ± 7.09° to 28.46° ± 4.18°, respectively; P = .011), and external rotation (59.66° ± 23.81° to 76.66° ± 18.30° vs 57.14°± 24.69° to 65.57° ± 26.39° for the PRP and corticosteroid groups, respectively; P = .036).²¹

Another RCT (N = 99) by Kwong et al²² comparing PRP to corticosteroids found similar short-term advantages of LP-PRP with an improved VAS score (–13.6 vs 0.4; P = .03), American Shoulder and Elbow Surgeons score (13.0 vs 2.9; P = .02), and Western Ontario Rotator Cuff Index score (16.8 vs 5.8; P = .03). However, there was no long-term benefit of PRP over corticosteroids found at 12 months.²²

A 2021 systematic review and meta-­analysis by Hamid et al²³ that included 8 RCTs (N = 976) favored PRP over control (no injection, saline injections, and/or shoulder rehabilitation) with improved VAS scores at 12 months (SMD = –0.5; 95% CI, –0.7 to –0.2; P < .001). The evidence on functional outcome was mixed. Data pooled from 2 studies (n = 228) found better Shoulder Pain and Disability Index (SPADI) scores compared to controls at 3- and 6-month follow-ups. However, there were no significant differences in Disabilities of the Arm, Shoulder and Hand (DASH) scores between the 2 groups.²³

Patellar tendinopathy

❯ ❯ ❯   Consider using PRP for return to sport

Patellar tendinopathy, a common MSK condition encountered in the primary care setting, has an overall prevalence of 22% in elite athletes at some point in their career.^{24 ­}Nonsurgical management options include rest, ice, eccentric and isometric exercises, anti-­inflammatory drugs, extracorporeal shock wave therapy (ESWT), and dry needling (DN).

Currently, corticosteroid injections are the only intraarticular therapy recommended by international guidelines for hip OA.

A 2014 RCT (N = 23) evaluating DN vs PRP for patellar tendinopathy favored PRP with improved VAS scores (mean ± SD = 25.4 ± 23.2 points; P = .01 vs 5.2 ± 12.5 points; P = .20) at 12 weeks (P = .02). However, at ≥ 26 weeks, the improvement in pain and function scores was similar between the DN and PRP groups (33.2 ± 14.0 points; P = .001 vs 28.9 ± 25.2 points; P = .01). Notably, there was significantly more improvement in the PRP group at 12 weeks (P = .02) but not at 26 weeks (P = .66).²⁵

Continue to: Another perspective study...

Another prospective study (N = 31) comparing PRP to physiotherapy showed a greater improvement in sport activity level reflected by the Tegner score in the PRP group (percentage improvement, 39 ± 22%) compared to control (20 ± 27%; P = .048) at 6 months.⁷

A recent RCT (N = 20) revealed improved VAS scores at 6 months with rehabilitation paired with either bone marrow mesenchymal stem cells (BM-MSC) or LP-PRP when compared with baseline (BM-MSC group: 4.23 ± 2.13 to 2.52 ± 2.37; P = .0621; LP-PRP group: 3.10 ± 1.20 to 1.13 ± 1.25; P = .0083). Pain was significantly reduced during sport play in both groups at 6 months when compared with baseline (BM-MSC group: 6.91 ± 1.11 to 3.06 ± 2.89, P = .0049; PRP group: 7.03 ± 1.42 to 1.94 ± 1.24, P = .0001).²⁶

A 2019 systematic review and meta-analysis (N = 2530) demonstrated greater improvements in Victorian Institute of Sport Assessment scale for patellar tendinopathy (VISA-P) with multiple injections of PRP (38.7 points; 95% CI, 26.3-51.2 points) compared to single injections of PRP (24.3 points; 95% CI, 18.2-30.5 points), eccentric exercise (28.3 points; 95% CI, 18.9-37.8 points) and ESWT (27.4 points; 95% CI, 10.0-39.8 points) after 6 months.²⁷ In contrast, an RCT (n = 57) comparing a single injection of LR-PRP or LP-PRP was no more effective than a single injection of saline for improvement in mean VISA-P scores (P > .05) at 1 year.²⁸

Lateral epicondylitis

❯ ❯ ❯   Consider using PRP

Lateral epicondylitis (“tennis elbow”) is caused by overuse of the elbow extensors at the site of the lateral epicondyle. Chronic lateral epicondylosis involves tissue degeneration and microtrauma. Most cases of epicondylar tendinopathies are treated nonoperatively, with corticosteroid injections being a mainstay of treatment despite their short-term benefit²⁹ and potential to deteriorate connective tissue over time. Recent studies suggest PRP therapy for epicondylitis and epicondylosis may increase long-term pain relief and improve function.

The evidence on functional outcome of platelet-rich plasma for rotator cuff tendinopathy is mixed.

A 2017 systematic review and meta-­analysis of 16 RCTs (N = 1018) concluded PRP was more efficacious than control injections (bupivacaine) for pain reduction in tendinopathies (effect size = 0.47; 95% CI, 0.22-0.72).³⁰ In the review, lateral epicondylitis was evaluated in 12 studies and was most responsive to PRP (effect size = 0.57) when compared to control injection.³⁰ In another systematic review (5 RCTs; 250 patients), corticosteroid injections improved pain within the first 6 weeks of treatment. However, PRP outperformed corticosteroid in VAS scores (21.3 ± 28.1 vs 42.4 ± 26.8) and DASH scores (17.6 ± 24.0 vs 36.5 ± 23.8) (P < .001) at 2 years.³¹

Continue to: A 2022 systematic review...

A 2022 systematic review and meta-­analysis (26 studies; N = 1040) comparing scores at baseline vs 2 years post-PRP showed improvement in VAS scores (7.4 ± 1.30 vs 3.71 ± 2.35; P < .001), DASH scores (60.8 ± 12.5 vs 13.0 ± 18.5; P < .001), Patient-Rated Tennis Elbow Evaluation (55.6 ± 14.7 vs 48.8 ± 4.1; P < .001), and Mayo Clinic Performance Index (55.5 ± 6.1 vs 93.0 ± 6.7; P < .001).³²

Regarding the therapeutic effects of different PRP types in lateral epicondylitis, a 2022 systematic review of 33 studies (N = 2420) found improved function and pain relief with LR-PRP and LP-PRP with no significant differences.³³ Pretreatment VAS scores in the LR-PRP group, which ranged from 6.1 to 8.0, improved to 1.5 to 4.0 at 3 months and 0.6 to 3.3 after 1 year.³³ Similarly, pretreatment VAS scores in the LP-PRP group, which ranged from 4.2 to 8.4, improved to 1.6 to 5.9 at 3 months and 0.7 to 2.7 after 1 year.³⁴ DASH scores also improved in the LR-PRP and LP-PRP groups, with pretreatment scores (LR-PRP, 47.0 to 54.3; LP-PRP, 30.0 to 67.7) improving to 20.0 to 22.0 and 5.5 to 19.0, respectively, at 1 year.³³

Achilles tendinopathy

❯ ❯ ❯   Do not use PRP; evidence is lacking

Achilles tendinopathy, caused by chronic overuse and overload resulting in microtrauma and poor tissue healing, typically occurs in the most poorly vascularized portion of the tendon and is common in runners. First-line treatments for Achilles tendinopathy include eccentric strength training and anti-­inflammatory drugs.^34,35 Corticosteroid injections are not recommended, given concern for degraded tendon tissue over time and worse function.³⁴

A 2020 systematic review of 11 randomized and nonrandomized clinical trials (N = 406) found PRP improved Victorian Institute of Sports Assessment—Achilles (VISA-A) scores at 24 weeks compared to other nonsurgical treatment options (41.2 vs 70.12; P < .018).³⁴ However, a higher-quality 2021 systematic review and meta-analysis of 4 RCTs (N = 170) comparing PRP injections with placebo showed no significant difference in VISA-A scores at 3 months (0.23; 95% CI, –0.45 to 0.91), 6 months (0.83; 95% CI, –0.26 to 1.92), and 12 months (0.83; 95% CI, –0.77 to 2.44).³⁶ Therefore, further studies are warranted to evaluate the benefit of PRP injections for Achilles tendinopathy.

Conclusions

While high-quality studies support the use of PRP for knee OA and lateral epicondylitis, they have a moderate-to-high risk for bias. Several RCTs show that PRP provides superior short-term pain relief and range of motion compared to corticosteroids for rotator cuff tendinopathy. Multiple injections of PRP for patellar tendinopathy may accelerate return to sport and improve symptoms over the long term. However, current evidence does not support PRP therapy for Achilles tendinopathy. Given variability in PRP preparation, an accurate interpretation of the literature regarding its use in MSK conditions is recommended (TABLE^{4,6,7,14-18,20-23,25-28,30-34,36}).

Continue to: Concerning the effectiveness of PRP...

Concerning the effectiveness of PRP, it is important to consider early publication bias. Although recent studies have shown its benefits,^6,14,15,37 additional studies comparing PRP to placebo will help demonstrate its efficacy. Interestingly, a literature search by Bar-Or et al³⁸ found intra-articular saline may have a therapeutic effect on knee OA and confound findings when used as a placebo.

RCT data showed no benefit with platelet-rich plasma in treating small-joint osteoarthritis.

Recognizing the presence or lack of clinically significant improvement in the literature is important. For example, while some recent studies have shown PRP exceeds the minimal clinically significant difference for knee OA and lateral epicondylitis, others have not.^32,37 A 2021 systematic review of 11 clinical practice guidelines for the use of PRP in knee OA found that 9 were “uncertain or unable to make a recommendation” and 2 recommended against it.³⁹

In its 2021 position statement for the responsible use of regenerative medicine, the American Medical Society for Sports Medicine includes guidance on integrating orthobiologics into clinical practice. The guideline emphasizes informed consent and provides an evidence-based rationale for using PRP in certain patient populations (lateral epicondylitis and younger patients with mild-to-­moderate knee OA), recommending its use only after exhausting other conservative options.⁴⁰ Patients should be referred to physicians with experience using PRP and image-guided procedures.

CORRESPONDENCE
Gregory D. Bentz Jr, MD, 3640 High Street Suite 3B, Portsmouth, VA 23707; bentzgd@evms.edu

CASE 1 Multiparous female with short-interval pregnancies desires contraception

A 24-year-old woman (G4P3) presents for a routine prenatal visit in the third trimester. Her last 2 pregnancies have occurred within 3 months of her prior birth. She endorses feeling overwhelmed with having 4 children under the age of 5 years, and she specifies that she would like to avoid another pregnancy for several years. She plans to breast and bottle feed, and she notes that she tends to forget to take pills. When you look back at her prior charts, you note that she did not return for her last 2 postpartum visits. What can you offer her? What would be a safe contraceptive option for her?
 

Intrauterine devices (IUDs) are safe, effective, and reported by patients to be satisfactory methods of contraception precisely because they are prone to less user error. The Contraceptive Choice Project demonstrated that patients are more apt to choose them when barriers such as cost and access are removed and nondirective counseling is provided.¹ Given that unintended pregnancy rates hover around 48%, the American College of Obstetricians and Gynecologists (ACOG) recommends them as first-line methods for pregnancy prevention.^2,3

For repeat pregnancies, the postpartum period is an especially vulnerable time—non-breastfeeding women will ovulate as soon as 25 days after birth, and by 8 weeks 30% will have ovulated.⁴ Approximately 40% to 57% of women report having unprotected intercourse before 6 weeks postpartum, and nearly 70% of all pregnancies in the first year postpartum are unintended.^3,5 Furthermore, patients at highest risk for short-interval pregnancy, such as adolescents, are less likely to return for a postpartum visit.³

Short-interval pregnancies confer greater fetal risk, including risks of low-birth weight, preterm birth, small for gestational age and increased risk of neonatal intensive care unit admission.⁶ Additionally, maternal health may be compromised during a short-interval pregnancy, particularly in medically complex patients due to increased risks of adverse pregnancy outcomes, such as postpartum bleeding or uterine rupture and disease progression.⁷ A 2006 meta-analysis by Conde-Agudelo and colleagues found that waiting at least 18 months between pregnancies was optimal for reducing these risks.⁶

Thus, the immediate postpartum period is an optimal time for addressing contraceptive needs and for preventing short-interval and unintended pregnancy. This article aims to provide evidence supporting the use of immediate postpartum IUDs, as well as their associated risks and barriers to use.

IUD types and routes for immediate postpartum insertion

There are several randomized controlled trials (RCTs) that examine the immediate postpartum use of copper IUDs and levonorgestrel-releasing (LNG) IUDs.^8-11 In 2010, Chen and colleagues compared placement of the immediate postpartum IUD following vaginal delivery with interval placement at 6–8 weeks postpartum. Of 51 patients enrolled in each arm, 98% received an IUD immediately postpartum, and 90% received one during their postpartum visit. There were 12 expulsions (24%) in the immediate postpartum IUD group, compared with 2 (4.4%) in the interval group. Expelled IUDs were replaced, and at 6 months both groups had similar rates of IUD use.⁸

Whitaker and colleagues demonstrated similar findings after randomizing a small group of women who had a cesarean delivery (CD) to interval or immediate placement. There were significantly more expulsions in the post-placental group (20%) than the interval group (0%), but there were more users of the IUD in the post-placental group than in the interval group at 12 months.⁹

Two RCTs, by Lester and colleagues and Levi et al, demonstrated successful placement of the copper IUD or LNG-IUD following CD, with few expulsions (0% and 8%, respectively). Patients who were randomized to immediate postpartum IUD placement were more likely to receive an IUD than those who were randomized to interval insertion, mostly due to lack of postpartum follow up. Both studies followed patients out to 6 months, and rates of IUD continuation and satisfaction were higher at this time in the immediate postpartum IUD groups.^10,11

Continue to: Risks, contraindications, and breastfeeding impact...

 

 

Risks, contraindications, and breastfeeding impact

What are the risks of immediate postpartum IUD placement? The highest risk of IUD placement in the immediate postpartum period appears to be expulsion (TABLE 1). In a meta-analysis conducted in 2022, which looked at 11 studies of immediate IUD insertion, the rates of expulsion were between 5% and 27%.^3,8,12,13 Results of a study by Cohen and colleagues demonstrated that most expulsions occurred within the first 12 weeks following delivery; of those expulsions that occurred, only 11% went unrecognized.¹³ Immediate postpartum IUD insertion does not increase the IUD-associated risks of perforation, infection, or immediate postpartum bleeding (although prolonged bleeding may be more common).¹²

Are there contraindications to placing an IUD immediately postpartum? The main contraindication to immediate postpartum IUD use is peripartum infection, including Triple I, endomyometritis, and puerperal sepsis. Other contraindications include retained placenta requiring manual or surgical removal, uterine anomalies, and other medical contraindications to IUD use as recommended by the US Medical Eligibility Criteria.¹⁴

Does immediate IUD placement affect breastfeeding? There is theoretical risk of decreased milk supply or difficulty breastfeeding with initiation of progestin-only methods of contraception in the immediate postpartum period, as the rapid fall in progesterone levels initiates lactogenesis. However, progestin-only methods appear to have limited effect on initiation and continuation of breastfeeding in the immediate postpartum period.¹⁵

There were 2 secondary analyses of a pair of RCTs comparing immediate and delayed postpartum IUD use. Results from Levi and colleagues demonstrated no difference between immediate and interval IUD placement groups in the proportion of women who were breastfeeding at 6, 12, and 24 weeks.¹⁶ Chen and colleagues’ study was smaller; researchers found that women with interval IUD placement were more likely to be exclusively breastfeeding and continuing to breastfeed at 6 months compared with the immediate postpartum group.¹⁷

To better characterize the impact of progestin implants, in a recent meta-analysis, authors examined the use of subcutaneous levonorgestrel rods and found no difference in breastfeeding initiation and continuation rates between women who had them placed immediately versus 6 ̶ 8 weeks postpartum.¹²

Benefits of immediate postpartum IUD placement

One benefit of immediate postpartum IUD insertion is a reduction in short-interval pregnancies. In a study by Cohen and colleagues¹³ of young women aged 13 to 22 years choosing immediate postpartum IUDs (82) or implants (162), the authors found that 61% of women retained their IUDs at 12 months postpartum. Because few requested IUD removal over that time frame, the discontinuation rate at 1 year was primarily due to expulsions. Pregnancy rates at 1 year were 7.6% in the IUD group and 1.5% in the implant group. However, the 7.6% rate in the IUD group was lower than in previously studied adolescent control groups: 18.6% of control adolescents (38 of 204) using a contraceptive form other than a postpartum etonogestrel implant had repeat pregnancy at 1 year.^13,18

Not only are patients who receive immediate postpartum IUDs more likely to receive them and continue their use, but they are also satisfied with the experience of receiving the IUD and with the method of contraception. A small mixed methods study of 66 patients demonstrated that women were interested in obtaining immediate postpartum contraception to avoid some of the logistical and financial challenges of returning for a postpartum visit. They also felt that the IUD placement was less painful than expected, and they didn’t feel that the insertion process imposed on their birth experience. Many described relief to know that they had a safe and effective contraceptive method upon leaving the hospital.¹⁹ Other studies have shown that even among women who expel an IUD following immediate postpartum placement, many choose to replace it in order to continue it as a contraceptive method.^8,9,13

Continue to: Instructions for placement...

 

 

Instructions for placement

1. Counsel appropriately. Thoroughly counsel patients regarding their options for postpartum contraception, with emphasis on the benefits, risks, and contraindications. Current recommendations to reduce the risk of expulsion are to place the IUD in the delivery room or operating room within 10 minutes of placental delivery.

2. Post ̶ vaginal delivery. Following vaginal delivery, remove the IUD from the inserter, cut the strings to 10 cm and, using either fingers to grasp the wings of the IUD or ring forceps, advance the IUD to the fundus. Ultrasound guidance may be used, but it does not appear to be helpful in preventing expulsion.²⁰

3. Post ̶ cesarean delivery. Once the placenta is delivered, place the IUD using the inserter or a ring forceps at the fundus and guide the strings into the cervix, then close the hysterotomy.

ACOG does recommend formal trainingbefore placing postpartum IUDs. One resource they provide is a free online webinar (https://www.acog.org/education-and-events/webinars/long-acting-reversible-contra ception-overview-and-hands-on-practice-for-residents).³

CASE 1 Resolved

The patient was counseled in the office about her options, and she was most interested in immediate postpartum LNG-IUD placement. She went on to deliver a healthy baby vaginally at 39 weeks. Within 10 minutes of placental delivery, she received an LNG-IUD. She returned to the office 3 months later for STI screening; her examination revealed correct placement and no evidence of expulsion. She expressed that she was happy with her IUD and thankful that she was able to receive it immediately after the birth of her baby.

CASE 2 Nulliparous woman desires IUD for postpartum contraception

A 33-year-old nulliparous woman presents in the third trimester for a routine prenatal visit. She had used the LNG-IUD prior to getting pregnant and reports that she was very happy with it. She knows she wants to wait at least 2 years before trying to get pregnant again, and she would like to resume contraception as soon as it is reasonably safe to do so. She has read that it is possible to get an IUD immediately postpartum and asks about it as a possible option.

What barriers will she face in obtaining an immediate postpartum IUD?

There are many barriers for patients who may be good candidates for immediate postpartum contraception (TABLE 2). Many patients are unaware that it is a safe option, and they often have concerns about such risks as infection, perforation, and effects on breastfeeding. Additionally, providers may not prioritize adequate counseling about postpartum contraception when they face time constraints and a need to counsel about other pregnancy-related topics during the prenatal visit schedule.^7,21

System, hospital, and clinician barriers to immediate postpartum IUD use

Hospital implementation of a successful postpartum IUD program requires pharmacy, intrapartum and postpartum nursing staff, physicians, administration, and billing to be aligned. Hospital administration and pharmacists must stock IUDs in the pharmacy. Hospital nursing staff attitudes toward and knowledge of postpartum contraception can have profound influence on how they discuss safe and effective methods of postpartum contraception with patients who may not have received counseling during prenatal care.²² In a survey of 108 ACOG fellows, nearly 75% of ObGyn physicians did not offer immediate postpartum IUDs; lack of provider training, lack of IUD availability, and concern about cost and payment were found to be common reasons why.²¹ Additionally, Catholic-affiliated and rural institutions are less likely to offer it, whereas more urban, teaching hospitals are more likely to have programs in place.²³ Prior to 2012, immediate postpartum IUD insertions and device costs were part of the global Medicaid obstetric fee in most states, and both hospital systems and individual providers were concerned about loss of revenue.²³

In 2015, Washington and colleagues published a decision analysis that examined the cost-effectiveness and cost savings associated with immediate postpartum IUD use. Accounting for expulsion rates, they found that immediate postpartum IUD placement can save $282,540 per 1,000 women over 2 years; additionally, immediate postpartum IUD use can prevent 88 unintended pregnancies per 1,000 women over 2 years.²⁴ Not only do immediate postpartum IUDs have great potential to prevent individual patients from undesired short-interval pregnancies (FIGURE 1), but they can also save the system substantial health care dollars (FIGURE 2).

Overcoming barriers

Immediate postpartum IUD implementation is attainable with practice, policy, and institutional changes. Education and training programs geared toward providers and nursing staff can improve understanding of the benefits and risks of immediate postpartum IUD placement. Additionally, clinicians must provide comprehensive, nondirective counseling during the antepartum period, informing patients of all safe and effective options. Expulsion risks should be disclosed, as well as the benefit of not needing to return for a separate postpartum contraception appointment.

Since 2012, many state Medicaid agencies have decoupled reimbursement for inpatient postpartum IUD insertion from the delivery fee. By 2018, more than half of states adopted this practice. Commercial insurers have followed suit in some cases, and as such, both Medicaid and commercially insured patients have had increased access to immediate postpartum IUDs.²³ This has translated into increased uptake of immediate postpartum IUDs among both Medicaid and commercially insured patients. Koch et al conducted a retrospective cohort study comparing IUD use in patients 1 year before and 1 year after the policy changes, and they found a 10-fold increase in use of immediate postpartum IUDs.²⁵

While education, counseling, access, and changes in reimbursement may increase access in many hospital systems, some barriers, such as religious affiliation of the hospital system, may be impossible to overcome. A viable alternative to immediate postpartum IUD placement may be early postpartum IUD placement, which could allow patients to coordinate this procedure with 1- or 2-week return routine postpartum visits for CD recovery, mental health screenings, and/or well-baby visits. More data are necessary before recommending this universally, but Averbach and colleagues published a promising meta-analysis that demonstrated no complete expulsions in studies in which IUDs were placed between 2 and 4 weeks postpartum, and only a pooled partial expulsion rate (of immediate postpartum, early inpatient, early outpatient, and interval placement) of 3.7%.⁴

CASE 2 Resolved

Although the patient was interested in receiving a postpartum LNG-IUD immediately after her vaginal birth, she had to wait until her 6-week postpartum visit. The hospital did not stock IUDs for immediate postpartum IUD use, and her provider, having not been trained on immediate postpartum insertion, did not feel comfortable trying to place it in the immediate postpartum time frame. ●

CASE 1 Multiparous female with short-interval pregnancies desires contraception

A 24-year-old woman (G4P3) presents for a routine prenatal visit in the third trimester. Her last 2 pregnancies have occurred within 3 months of her prior birth. She endorses feeling overwhelmed with having 4 children under the age of 5 years, and she specifies that she would like to avoid another pregnancy for several years. She plans to breast and bottle feed, and she notes that she tends to forget to take pills. When you look back at her prior charts, you note that she did not return for her last 2 postpartum visits. What can you offer her? What would be a safe contraceptive option for her?
 

Intrauterine devices (IUDs) are safe, effective, and reported by patients to be satisfactory methods of contraception precisely because they are prone to less user error. The Contraceptive Choice Project demonstrated that patients are more apt to choose them when barriers such as cost and access are removed and nondirective counseling is provided.¹ Given that unintended pregnancy rates hover around 48%, the American College of Obstetricians and Gynecologists (ACOG) recommends them as first-line methods for pregnancy prevention.^2,3

For repeat pregnancies, the postpartum period is an especially vulnerable time—non-breastfeeding women will ovulate as soon as 25 days after birth, and by 8 weeks 30% will have ovulated.⁴ Approximately 40% to 57% of women report having unprotected intercourse before 6 weeks postpartum, and nearly 70% of all pregnancies in the first year postpartum are unintended.^3,5 Furthermore, patients at highest risk for short-interval pregnancy, such as adolescents, are less likely to return for a postpartum visit.³

Short-interval pregnancies confer greater fetal risk, including risks of low-birth weight, preterm birth, small for gestational age and increased risk of neonatal intensive care unit admission.⁶ Additionally, maternal health may be compromised during a short-interval pregnancy, particularly in medically complex patients due to increased risks of adverse pregnancy outcomes, such as postpartum bleeding or uterine rupture and disease progression.⁷ A 2006 meta-analysis by Conde-Agudelo and colleagues found that waiting at least 18 months between pregnancies was optimal for reducing these risks.⁶

Thus, the immediate postpartum period is an optimal time for addressing contraceptive needs and for preventing short-interval and unintended pregnancy. This article aims to provide evidence supporting the use of immediate postpartum IUDs, as well as their associated risks and barriers to use.

IUD types and routes for immediate postpartum insertion

There are several randomized controlled trials (RCTs) that examine the immediate postpartum use of copper IUDs and levonorgestrel-releasing (LNG) IUDs.^8-11 In 2010, Chen and colleagues compared placement of the immediate postpartum IUD following vaginal delivery with interval placement at 6–8 weeks postpartum. Of 51 patients enrolled in each arm, 98% received an IUD immediately postpartum, and 90% received one during their postpartum visit. There were 12 expulsions (24%) in the immediate postpartum IUD group, compared with 2 (4.4%) in the interval group. Expelled IUDs were replaced, and at 6 months both groups had similar rates of IUD use.⁸

Whitaker and colleagues demonstrated similar findings after randomizing a small group of women who had a cesarean delivery (CD) to interval or immediate placement. There were significantly more expulsions in the post-placental group (20%) than the interval group (0%), but there were more users of the IUD in the post-placental group than in the interval group at 12 months.⁹

Two RCTs, by Lester and colleagues and Levi et al, demonstrated successful placement of the copper IUD or LNG-IUD following CD, with few expulsions (0% and 8%, respectively). Patients who were randomized to immediate postpartum IUD placement were more likely to receive an IUD than those who were randomized to interval insertion, mostly due to lack of postpartum follow up. Both studies followed patients out to 6 months, and rates of IUD continuation and satisfaction were higher at this time in the immediate postpartum IUD groups.^10,11

Continue to: Risks, contraindications, and breastfeeding impact...

 

 

Risks, contraindications, and breastfeeding impact

What are the risks of immediate postpartum IUD placement? The highest risk of IUD placement in the immediate postpartum period appears to be expulsion (TABLE 1). In a meta-analysis conducted in 2022, which looked at 11 studies of immediate IUD insertion, the rates of expulsion were between 5% and 27%.^3,8,12,13 Results of a study by Cohen and colleagues demonstrated that most expulsions occurred within the first 12 weeks following delivery; of those expulsions that occurred, only 11% went unrecognized.¹³ Immediate postpartum IUD insertion does not increase the IUD-associated risks of perforation, infection, or immediate postpartum bleeding (although prolonged bleeding may be more common).¹²

Are there contraindications to placing an IUD immediately postpartum? The main contraindication to immediate postpartum IUD use is peripartum infection, including Triple I, endomyometritis, and puerperal sepsis. Other contraindications include retained placenta requiring manual or surgical removal, uterine anomalies, and other medical contraindications to IUD use as recommended by the US Medical Eligibility Criteria.¹⁴

Does immediate IUD placement affect breastfeeding? There is theoretical risk of decreased milk supply or difficulty breastfeeding with initiation of progestin-only methods of contraception in the immediate postpartum period, as the rapid fall in progesterone levels initiates lactogenesis. However, progestin-only methods appear to have limited effect on initiation and continuation of breastfeeding in the immediate postpartum period.¹⁵

There were 2 secondary analyses of a pair of RCTs comparing immediate and delayed postpartum IUD use. Results from Levi and colleagues demonstrated no difference between immediate and interval IUD placement groups in the proportion of women who were breastfeeding at 6, 12, and 24 weeks.¹⁶ Chen and colleagues’ study was smaller; researchers found that women with interval IUD placement were more likely to be exclusively breastfeeding and continuing to breastfeed at 6 months compared with the immediate postpartum group.¹⁷

To better characterize the impact of progestin implants, in a recent meta-analysis, authors examined the use of subcutaneous levonorgestrel rods and found no difference in breastfeeding initiation and continuation rates between women who had them placed immediately versus 6 ̶ 8 weeks postpartum.¹²

Benefits of immediate postpartum IUD placement

One benefit of immediate postpartum IUD insertion is a reduction in short-interval pregnancies. In a study by Cohen and colleagues¹³ of young women aged 13 to 22 years choosing immediate postpartum IUDs (82) or implants (162), the authors found that 61% of women retained their IUDs at 12 months postpartum. Because few requested IUD removal over that time frame, the discontinuation rate at 1 year was primarily due to expulsions. Pregnancy rates at 1 year were 7.6% in the IUD group and 1.5% in the implant group. However, the 7.6% rate in the IUD group was lower than in previously studied adolescent control groups: 18.6% of control adolescents (38 of 204) using a contraceptive form other than a postpartum etonogestrel implant had repeat pregnancy at 1 year.^13,18

Not only are patients who receive immediate postpartum IUDs more likely to receive them and continue their use, but they are also satisfied with the experience of receiving the IUD and with the method of contraception. A small mixed methods study of 66 patients demonstrated that women were interested in obtaining immediate postpartum contraception to avoid some of the logistical and financial challenges of returning for a postpartum visit. They also felt that the IUD placement was less painful than expected, and they didn’t feel that the insertion process imposed on their birth experience. Many described relief to know that they had a safe and effective contraceptive method upon leaving the hospital.¹⁹ Other studies have shown that even among women who expel an IUD following immediate postpartum placement, many choose to replace it in order to continue it as a contraceptive method.^8,9,13

Continue to: Instructions for placement...

 

 

Instructions for placement

1. Counsel appropriately. Thoroughly counsel patients regarding their options for postpartum contraception, with emphasis on the benefits, risks, and contraindications. Current recommendations to reduce the risk of expulsion are to place the IUD in the delivery room or operating room within 10 minutes of placental delivery.

2. Post ̶ vaginal delivery. Following vaginal delivery, remove the IUD from the inserter, cut the strings to 10 cm and, using either fingers to grasp the wings of the IUD or ring forceps, advance the IUD to the fundus. Ultrasound guidance may be used, but it does not appear to be helpful in preventing expulsion.²⁰

3. Post ̶ cesarean delivery. Once the placenta is delivered, place the IUD using the inserter or a ring forceps at the fundus and guide the strings into the cervix, then close the hysterotomy.

ACOG does recommend formal trainingbefore placing postpartum IUDs. One resource they provide is a free online webinar (https://www.acog.org/education-and-events/webinars/long-acting-reversible-contra ception-overview-and-hands-on-practice-for-residents).³

CASE 1 Resolved

The patient was counseled in the office about her options, and she was most interested in immediate postpartum LNG-IUD placement. She went on to deliver a healthy baby vaginally at 39 weeks. Within 10 minutes of placental delivery, she received an LNG-IUD. She returned to the office 3 months later for STI screening; her examination revealed correct placement and no evidence of expulsion. She expressed that she was happy with her IUD and thankful that she was able to receive it immediately after the birth of her baby.

CASE 2 Nulliparous woman desires IUD for postpartum contraception

A 33-year-old nulliparous woman presents in the third trimester for a routine prenatal visit. She had used the LNG-IUD prior to getting pregnant and reports that she was very happy with it. She knows she wants to wait at least 2 years before trying to get pregnant again, and she would like to resume contraception as soon as it is reasonably safe to do so. She has read that it is possible to get an IUD immediately postpartum and asks about it as a possible option.

What barriers will she face in obtaining an immediate postpartum IUD?

There are many barriers for patients who may be good candidates for immediate postpartum contraception (TABLE 2). Many patients are unaware that it is a safe option, and they often have concerns about such risks as infection, perforation, and effects on breastfeeding. Additionally, providers may not prioritize adequate counseling about postpartum contraception when they face time constraints and a need to counsel about other pregnancy-related topics during the prenatal visit schedule.^7,21

System, hospital, and clinician barriers to immediate postpartum IUD use

Hospital implementation of a successful postpartum IUD program requires pharmacy, intrapartum and postpartum nursing staff, physicians, administration, and billing to be aligned. Hospital administration and pharmacists must stock IUDs in the pharmacy. Hospital nursing staff attitudes toward and knowledge of postpartum contraception can have profound influence on how they discuss safe and effective methods of postpartum contraception with patients who may not have received counseling during prenatal care.²² In a survey of 108 ACOG fellows, nearly 75% of ObGyn physicians did not offer immediate postpartum IUDs; lack of provider training, lack of IUD availability, and concern about cost and payment were found to be common reasons why.²¹ Additionally, Catholic-affiliated and rural institutions are less likely to offer it, whereas more urban, teaching hospitals are more likely to have programs in place.²³ Prior to 2012, immediate postpartum IUD insertions and device costs were part of the global Medicaid obstetric fee in most states, and both hospital systems and individual providers were concerned about loss of revenue.²³

In 2015, Washington and colleagues published a decision analysis that examined the cost-effectiveness and cost savings associated with immediate postpartum IUD use. Accounting for expulsion rates, they found that immediate postpartum IUD placement can save $282,540 per 1,000 women over 2 years; additionally, immediate postpartum IUD use can prevent 88 unintended pregnancies per 1,000 women over 2 years.²⁴ Not only do immediate postpartum IUDs have great potential to prevent individual patients from undesired short-interval pregnancies (FIGURE 1), but they can also save the system substantial health care dollars (FIGURE 2).

Overcoming barriers

Immediate postpartum IUD implementation is attainable with practice, policy, and institutional changes. Education and training programs geared toward providers and nursing staff can improve understanding of the benefits and risks of immediate postpartum IUD placement. Additionally, clinicians must provide comprehensive, nondirective counseling during the antepartum period, informing patients of all safe and effective options. Expulsion risks should be disclosed, as well as the benefit of not needing to return for a separate postpartum contraception appointment.

Since 2012, many state Medicaid agencies have decoupled reimbursement for inpatient postpartum IUD insertion from the delivery fee. By 2018, more than half of states adopted this practice. Commercial insurers have followed suit in some cases, and as such, both Medicaid and commercially insured patients have had increased access to immediate postpartum IUDs.²³ This has translated into increased uptake of immediate postpartum IUDs among both Medicaid and commercially insured patients. Koch et al conducted a retrospective cohort study comparing IUD use in patients 1 year before and 1 year after the policy changes, and they found a 10-fold increase in use of immediate postpartum IUDs.²⁵

While education, counseling, access, and changes in reimbursement may increase access in many hospital systems, some barriers, such as religious affiliation of the hospital system, may be impossible to overcome. A viable alternative to immediate postpartum IUD placement may be early postpartum IUD placement, which could allow patients to coordinate this procedure with 1- or 2-week return routine postpartum visits for CD recovery, mental health screenings, and/or well-baby visits. More data are necessary before recommending this universally, but Averbach and colleagues published a promising meta-analysis that demonstrated no complete expulsions in studies in which IUDs were placed between 2 and 4 weeks postpartum, and only a pooled partial expulsion rate (of immediate postpartum, early inpatient, early outpatient, and interval placement) of 3.7%.⁴

CASE 2 Resolved

Although the patient was interested in receiving a postpartum LNG-IUD immediately after her vaginal birth, she had to wait until her 6-week postpartum visit. The hospital did not stock IUDs for immediate postpartum IUD use, and her provider, having not been trained on immediate postpartum insertion, did not feel comfortable trying to place it in the immediate postpartum time frame. ●

CASE 1 Multiparous female with short-interval pregnancies desires contraception

A 24-year-old woman (G4P3) presents for a routine prenatal visit in the third trimester. Her last 2 pregnancies have occurred within 3 months of her prior birth. She endorses feeling overwhelmed with having 4 children under the age of 5 years, and she specifies that she would like to avoid another pregnancy for several years. She plans to breast and bottle feed, and she notes that she tends to forget to take pills. When you look back at her prior charts, you note that she did not return for her last 2 postpartum visits. What can you offer her? What would be a safe contraceptive option for her?
 

Intrauterine devices (IUDs) are safe, effective, and reported by patients to be satisfactory methods of contraception precisely because they are prone to less user error. The Contraceptive Choice Project demonstrated that patients are more apt to choose them when barriers such as cost and access are removed and nondirective counseling is provided.¹ Given that unintended pregnancy rates hover around 48%, the American College of Obstetricians and Gynecologists (ACOG) recommends them as first-line methods for pregnancy prevention.^2,3

For repeat pregnancies, the postpartum period is an especially vulnerable time—non-breastfeeding women will ovulate as soon as 25 days after birth, and by 8 weeks 30% will have ovulated.⁴ Approximately 40% to 57% of women report having unprotected intercourse before 6 weeks postpartum, and nearly 70% of all pregnancies in the first year postpartum are unintended.^3,5 Furthermore, patients at highest risk for short-interval pregnancy, such as adolescents, are less likely to return for a postpartum visit.³

Short-interval pregnancies confer greater fetal risk, including risks of low-birth weight, preterm birth, small for gestational age and increased risk of neonatal intensive care unit admission.⁶ Additionally, maternal health may be compromised during a short-interval pregnancy, particularly in medically complex patients due to increased risks of adverse pregnancy outcomes, such as postpartum bleeding or uterine rupture and disease progression.⁷ A 2006 meta-analysis by Conde-Agudelo and colleagues found that waiting at least 18 months between pregnancies was optimal for reducing these risks.⁶

Thus, the immediate postpartum period is an optimal time for addressing contraceptive needs and for preventing short-interval and unintended pregnancy. This article aims to provide evidence supporting the use of immediate postpartum IUDs, as well as their associated risks and barriers to use.

IUD types and routes for immediate postpartum insertion

There are several randomized controlled trials (RCTs) that examine the immediate postpartum use of copper IUDs and levonorgestrel-releasing (LNG) IUDs.^8-11 In 2010, Chen and colleagues compared placement of the immediate postpartum IUD following vaginal delivery with interval placement at 6–8 weeks postpartum. Of 51 patients enrolled in each arm, 98% received an IUD immediately postpartum, and 90% received one during their postpartum visit. There were 12 expulsions (24%) in the immediate postpartum IUD group, compared with 2 (4.4%) in the interval group. Expelled IUDs were replaced, and at 6 months both groups had similar rates of IUD use.⁸

Whitaker and colleagues demonstrated similar findings after randomizing a small group of women who had a cesarean delivery (CD) to interval or immediate placement. There were significantly more expulsions in the post-placental group (20%) than the interval group (0%), but there were more users of the IUD in the post-placental group than in the interval group at 12 months.⁹

Two RCTs, by Lester and colleagues and Levi et al, demonstrated successful placement of the copper IUD or LNG-IUD following CD, with few expulsions (0% and 8%, respectively). Patients who were randomized to immediate postpartum IUD placement were more likely to receive an IUD than those who were randomized to interval insertion, mostly due to lack of postpartum follow up. Both studies followed patients out to 6 months, and rates of IUD continuation and satisfaction were higher at this time in the immediate postpartum IUD groups.^10,11

Continue to: Risks, contraindications, and breastfeeding impact...

 

 

Risks, contraindications, and breastfeeding impact

What are the risks of immediate postpartum IUD placement? The highest risk of IUD placement in the immediate postpartum period appears to be expulsion (TABLE 1). In a meta-analysis conducted in 2022, which looked at 11 studies of immediate IUD insertion, the rates of expulsion were between 5% and 27%.^3,8,12,13 Results of a study by Cohen and colleagues demonstrated that most expulsions occurred within the first 12 weeks following delivery; of those expulsions that occurred, only 11% went unrecognized.¹³ Immediate postpartum IUD insertion does not increase the IUD-associated risks of perforation, infection, or immediate postpartum bleeding (although prolonged bleeding may be more common).¹²

Are there contraindications to placing an IUD immediately postpartum? The main contraindication to immediate postpartum IUD use is peripartum infection, including Triple I, endomyometritis, and puerperal sepsis. Other contraindications include retained placenta requiring manual or surgical removal, uterine anomalies, and other medical contraindications to IUD use as recommended by the US Medical Eligibility Criteria.¹⁴

Does immediate IUD placement affect breastfeeding? There is theoretical risk of decreased milk supply or difficulty breastfeeding with initiation of progestin-only methods of contraception in the immediate postpartum period, as the rapid fall in progesterone levels initiates lactogenesis. However, progestin-only methods appear to have limited effect on initiation and continuation of breastfeeding in the immediate postpartum period.¹⁵

There were 2 secondary analyses of a pair of RCTs comparing immediate and delayed postpartum IUD use. Results from Levi and colleagues demonstrated no difference between immediate and interval IUD placement groups in the proportion of women who were breastfeeding at 6, 12, and 24 weeks.¹⁶ Chen and colleagues’ study was smaller; researchers found that women with interval IUD placement were more likely to be exclusively breastfeeding and continuing to breastfeed at 6 months compared with the immediate postpartum group.¹⁷

To better characterize the impact of progestin implants, in a recent meta-analysis, authors examined the use of subcutaneous levonorgestrel rods and found no difference in breastfeeding initiation and continuation rates between women who had them placed immediately versus 6 ̶ 8 weeks postpartum.¹²

Benefits of immediate postpartum IUD placement

One benefit of immediate postpartum IUD insertion is a reduction in short-interval pregnancies. In a study by Cohen and colleagues¹³ of young women aged 13 to 22 years choosing immediate postpartum IUDs (82) or implants (162), the authors found that 61% of women retained their IUDs at 12 months postpartum. Because few requested IUD removal over that time frame, the discontinuation rate at 1 year was primarily due to expulsions. Pregnancy rates at 1 year were 7.6% in the IUD group and 1.5% in the implant group. However, the 7.6% rate in the IUD group was lower than in previously studied adolescent control groups: 18.6% of control adolescents (38 of 204) using a contraceptive form other than a postpartum etonogestrel implant had repeat pregnancy at 1 year.^13,18

Not only are patients who receive immediate postpartum IUDs more likely to receive them and continue their use, but they are also satisfied with the experience of receiving the IUD and with the method of contraception. A small mixed methods study of 66 patients demonstrated that women were interested in obtaining immediate postpartum contraception to avoid some of the logistical and financial challenges of returning for a postpartum visit. They also felt that the IUD placement was less painful than expected, and they didn’t feel that the insertion process imposed on their birth experience. Many described relief to know that they had a safe and effective contraceptive method upon leaving the hospital.¹⁹ Other studies have shown that even among women who expel an IUD following immediate postpartum placement, many choose to replace it in order to continue it as a contraceptive method.^8,9,13

Continue to: Instructions for placement...

 

 

Instructions for placement

1. Counsel appropriately. Thoroughly counsel patients regarding their options for postpartum contraception, with emphasis on the benefits, risks, and contraindications. Current recommendations to reduce the risk of expulsion are to place the IUD in the delivery room or operating room within 10 minutes of placental delivery.

2. Post ̶ vaginal delivery. Following vaginal delivery, remove the IUD from the inserter, cut the strings to 10 cm and, using either fingers to grasp the wings of the IUD or ring forceps, advance the IUD to the fundus. Ultrasound guidance may be used, but it does not appear to be helpful in preventing expulsion.²⁰

3. Post ̶ cesarean delivery. Once the placenta is delivered, place the IUD using the inserter or a ring forceps at the fundus and guide the strings into the cervix, then close the hysterotomy.

ACOG does recommend formal trainingbefore placing postpartum IUDs. One resource they provide is a free online webinar (https://www.acog.org/education-and-events/webinars/long-acting-reversible-contra ception-overview-and-hands-on-practice-for-residents).³

CASE 1 Resolved

The patient was counseled in the office about her options, and she was most interested in immediate postpartum LNG-IUD placement. She went on to deliver a healthy baby vaginally at 39 weeks. Within 10 minutes of placental delivery, she received an LNG-IUD. She returned to the office 3 months later for STI screening; her examination revealed correct placement and no evidence of expulsion. She expressed that she was happy with her IUD and thankful that she was able to receive it immediately after the birth of her baby.

CASE 2 Nulliparous woman desires IUD for postpartum contraception

A 33-year-old nulliparous woman presents in the third trimester for a routine prenatal visit. She had used the LNG-IUD prior to getting pregnant and reports that she was very happy with it. She knows she wants to wait at least 2 years before trying to get pregnant again, and she would like to resume contraception as soon as it is reasonably safe to do so. She has read that it is possible to get an IUD immediately postpartum and asks about it as a possible option.

What barriers will she face in obtaining an immediate postpartum IUD?

There are many barriers for patients who may be good candidates for immediate postpartum contraception (TABLE 2). Many patients are unaware that it is a safe option, and they often have concerns about such risks as infection, perforation, and effects on breastfeeding. Additionally, providers may not prioritize adequate counseling about postpartum contraception when they face time constraints and a need to counsel about other pregnancy-related topics during the prenatal visit schedule.^7,21

System, hospital, and clinician barriers to immediate postpartum IUD use

Hospital implementation of a successful postpartum IUD program requires pharmacy, intrapartum and postpartum nursing staff, physicians, administration, and billing to be aligned. Hospital administration and pharmacists must stock IUDs in the pharmacy. Hospital nursing staff attitudes toward and knowledge of postpartum contraception can have profound influence on how they discuss safe and effective methods of postpartum contraception with patients who may not have received counseling during prenatal care.²² In a survey of 108 ACOG fellows, nearly 75% of ObGyn physicians did not offer immediate postpartum IUDs; lack of provider training, lack of IUD availability, and concern about cost and payment were found to be common reasons why.²¹ Additionally, Catholic-affiliated and rural institutions are less likely to offer it, whereas more urban, teaching hospitals are more likely to have programs in place.²³ Prior to 2012, immediate postpartum IUD insertions and device costs were part of the global Medicaid obstetric fee in most states, and both hospital systems and individual providers were concerned about loss of revenue.²³

In 2015, Washington and colleagues published a decision analysis that examined the cost-effectiveness and cost savings associated with immediate postpartum IUD use. Accounting for expulsion rates, they found that immediate postpartum IUD placement can save $282,540 per 1,000 women over 2 years; additionally, immediate postpartum IUD use can prevent 88 unintended pregnancies per 1,000 women over 2 years.²⁴ Not only do immediate postpartum IUDs have great potential to prevent individual patients from undesired short-interval pregnancies (FIGURE 1), but they can also save the system substantial health care dollars (FIGURE 2).

Overcoming barriers

Immediate postpartum IUD implementation is attainable with practice, policy, and institutional changes. Education and training programs geared toward providers and nursing staff can improve understanding of the benefits and risks of immediate postpartum IUD placement. Additionally, clinicians must provide comprehensive, nondirective counseling during the antepartum period, informing patients of all safe and effective options. Expulsion risks should be disclosed, as well as the benefit of not needing to return for a separate postpartum contraception appointment.

Since 2012, many state Medicaid agencies have decoupled reimbursement for inpatient postpartum IUD insertion from the delivery fee. By 2018, more than half of states adopted this practice. Commercial insurers have followed suit in some cases, and as such, both Medicaid and commercially insured patients have had increased access to immediate postpartum IUDs.²³ This has translated into increased uptake of immediate postpartum IUDs among both Medicaid and commercially insured patients. Koch et al conducted a retrospective cohort study comparing IUD use in patients 1 year before and 1 year after the policy changes, and they found a 10-fold increase in use of immediate postpartum IUDs.²⁵

While education, counseling, access, and changes in reimbursement may increase access in many hospital systems, some barriers, such as religious affiliation of the hospital system, may be impossible to overcome. A viable alternative to immediate postpartum IUD placement may be early postpartum IUD placement, which could allow patients to coordinate this procedure with 1- or 2-week return routine postpartum visits for CD recovery, mental health screenings, and/or well-baby visits. More data are necessary before recommending this universally, but Averbach and colleagues published a promising meta-analysis that demonstrated no complete expulsions in studies in which IUDs were placed between 2 and 4 weeks postpartum, and only a pooled partial expulsion rate (of immediate postpartum, early inpatient, early outpatient, and interval placement) of 3.7%.⁴

CASE 2 Resolved

Although the patient was interested in receiving a postpartum LNG-IUD immediately after her vaginal birth, she had to wait until her 6-week postpartum visit. The hospital did not stock IUDs for immediate postpartum IUD use, and her provider, having not been trained on immediate postpartum insertion, did not feel comfortable trying to place it in the immediate postpartum time frame. ●

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, although it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE (particularly in those with skin of color), as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/ Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4

Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphospholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8
• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have farreaching effects, negatively impacting quality of life and even mortality.

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, although it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE (particularly in those with skin of color), as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/ Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4

Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphospholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8
• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have farreaching effects, negatively impacting quality of life and even mortality.

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, although it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE (particularly in those with skin of color), as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/ Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4

Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphospholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8
• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have farreaching effects, negatively impacting quality of life and even mortality.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.