While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at PAeditor@mdedge.com. See you next Thursday!

While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at PAeditor@mdedge.com. See you next Thursday!

While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at PAeditor@mdedge.com. See you next Thursday!

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky

The average life expectancy in the United States declined from 78.9 years in 2014 to 78.6 years in 2017.¹ The 2017 figure—78.6 years—means life expectancy is shorter in the United States than in other countries.¹ The decline is due, in part, to the drug overdose epidemic in the United States.² In 2017, 70,237 people died by drug overdose²—with prescription drugs, heroin, and opioids (especially fentanyl) being the major threats.³ From 2016 to 2017, overdoses from synthetic opioids, such as fentanyl, fentanyl analogs, and tramadol, increased from 6.2 to 9 per 100,000 people.²

The decline in life expectancy is due, in part, to the drug overdose epidemic in the United States.

These statistics should motivate all health care professionals to improve the general public’s health metrics, especially when treating patients with substance use disorders. But to best do so, we need a collaborative effort across many professions—not just health care providers, but also public health officials, elected government leaders, and law enforcement. To better define what this would entail, we suggest ways in which these groups could expand their roles to help reduce overdose deaths.

Health care professionals:

• implement safer opioid prescribing for patients who have chronic pain;
• educate patients about the risks of opioid use;
• consider alternative therapies for pain management; and
• utilize electronic databases to monitor controlled substance prescribing.

Public health officials:

• expand naloxone distribution; and
• enhance harm reduction (eg, syringe exchange programs, substance abuse treatment options).

Government leaders:

• draft legislation that allows the use of better interventions for treating individuals with drug dependence or those who overdose; and
• improve criminal justice approaches so that laws are less punitive and more therapeutic for individuals who suffer from drug dependence.

Law enforcement:

• supply naltrexone kits to first responders and provide appropriate training.

Kuldeep Ghosh, MD, MS
Rajashekhar Yeruva, MD
Steven Lippmann, MD
Louisville, Ky

A recent letter, “Hypoglycemia in the elderly: Watch for atypical symptoms” (J Fam Pract. 2019;68:116) provided an incomplete list of the letter’s authors. The list should have read: Jan Brož, MD, Jana Urbanová, MD, PhD, Prague, Czech Republic; Brian M. Frier, MD, BSc, Edinburgh, United Kingdom.

A recent letter, “Hypoglycemia in the elderly: Watch for atypical symptoms” (J Fam Pract. 2019;68:116) provided an incomplete list of the letter’s authors. The list should have read: Jan Brož, MD, Jana Urbanová, MD, PhD, Prague, Czech Republic; Brian M. Frier, MD, BSc, Edinburgh, United Kingdom.

A recent letter, “Hypoglycemia in the elderly: Watch for atypical symptoms” (J Fam Pract. 2019;68:116) provided an incomplete list of the letter’s authors. The list should have read: Jan Brož, MD, Jana Urbanová, MD, PhD, Prague, Czech Republic; Brian M. Frier, MD, BSc, Edinburgh, United Kingdom.

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Auricular perichondritis

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Auricular perichondritis

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Auricular perichondritis

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.