CASE Mr. J, a 75-year-old man, presents to your family practice reporting that he feels increasingly unsteady and slow while walking. He fell twice last year, without resulting injury. He now worries about tripping while walking around the house and relies on his spouse to run errands.

Almost 30% of people older than 65 years report 1 or more falls annually.

Clearly, Mr. J is experiencing a problem with balance. What management approach should you undertake to prevent him from falling?

Copyright Scott Bodell

Balance disorders are common in older people and drastically hinder quality of life.^1-4 Patients often describe imbalance as vague symptoms: dizziness, unsteadiness, faintness, spinning sensations.^5,6 Importantly, balance disorders disrupt normal gait and contribute to falls that are a major cause of disability and morbidity in older people. Almost 30% of people older than 65 years report 1 or more falls annually.⁷ Factors that increase the risk of falls include impaired mobility, previously reported falls, reduced psychological functioning, chronic medical conditions, and polypharmacy.^7,8

The cause of any single case of imbalance is often multifactorial, resulting from dysfunction of multiple body systems (TABLE 1^7-56); in our clinical experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system. These alterations in function arise in 3 key systems—vision, proprioception, and vestibular function—which signal to, and are incorporated by, the cerebellum to mediate balance. Cognitive and neurologic decline are also factors in imbalance.

Considering that 20% of falls result in serious injury in older populations, it is important to identify balance disorders and implement preventive strategies to mitigate harmful consequences of falls on patients’ health and independence.^7,57 In this article, we answer the question that the case presentation raises about the proper management approach to imbalance in family practice, including assessment of risk and rehabilitation strategies to reduce the risk of falls. Our insights and recommendations are based on our clinical experience and a review of the medical literature from the past 40 years.

CASE Mr. J has a history of hypertension, age-­related hearing loss, and osteoarthritis of the knees; he has not had surgery for the arthritis. His medications are antihypertensives and extra-strength acetaminophen for knee pain.

Making the diagnosis of a balance disorder

History

A thorough clinical history, often including a collateral history from caregivers, narrows the differential diagnosis. Information regarding onset, duration, timing, character, and previous episodes of imbalance is essential. Symptoms of imbalance are often challenging for the patient to describe: They might use terms such as vertigo or dizziness, when, in fact, on further questioning, they are describing balance difficulties. Inquiry into (1) their use of assistive walking devices and (2) development or exacerbation of neurologic, musculoskeletal, auditory, visual, and mood symptoms is necessary. Note the current level of their mobility, episodes of pain or fatigue, previous falls and associated injuries, fear of falling, balance confidence, and sensations that precede falls.⁵⁸

Continue to: The medical and surgical histories

The medical and surgical histories are key pieces of information. The history of smoking, alcohol habits, and substance use is relevant.

A robust medication history is essential to evaluate a patient’s risk of falling. Polypharmacy—typically, defined as taking 4 or more medications—has been repeatedly associated with a heightened risk of falls.^53,59-61 Moreover, a dose-dependent association between polypharmacy and hospitalization following falls has been identified, and demonstrates that taking 10 or more medications greatly increases the risk of hospitalization.⁵⁹ Studies of polypharmacy cement the importance of inquiring about medication use when assessing imbalance, particularly in older patients.

Physical examination

A focused and detailed physical examination provides insight into systems that should be investigated:

• Obtain vital signs, including orthostatic vitals to test for orthostatic hypotension⁶²; keep in mind that symptoms of orthostatic dizziness can occur without orthostatic hypotension.
• Examine gait, which can distinguish between causes of imbalance (TABLE 2).^21,40,63-70
• Perform a cardiac examination.
• Assess visual acuity and visual fields; test for nystagmus and identify any optic-nerve and retinal abnormalities.
• Evaluate lower-limb sensation, proprioception, and motor function.
• Evaluate suspected vestibular dysfunction, including dysfunction with positional testing (the Dix-Hallpike maneuver⁷¹). The patient is taken from sitting to supine while the head is rotated 45° to the tested side by the examiner. As the patient moves into a supine position, the neck is extended 30° off the table and held for at least 30 seconds. The maneuver is positive if torsional nystagmus is noted while the head is held rotated during neck extension. The maneuver is negative if the patient reports dizziness, vertigo, unsteadiness, or “pressure in the head.” Torsional nystagmus must be present to confirm a diagnosis of benign paroxysmal positional vertigo.
• If you suspect a central nervous system cause of imbalance, assess the cranial nerves, coordination, strength, and, of course, balance.

CASE

Mr. J’s physical examination showed normal vital signs without significant postural changes in blood pressure. Gait analysis revealed a slowed gait, with reduced range of motion in both knees over the entire gait cycle. Audiometry revealed symmetric moderate sensorineural hearing loss characteristic of presbycusis.

Diagnostic investigations

Consider focused investigations into imbalance based on the history and physical examination. We discourage overly broad testing and imaging; in primary care, cost and limited access to technology can bar robust investigations into causes of imbalance. However, identification of acute pathologies should prompt immediate referral to the emergency department. Furthermore, specific symptoms (TABLE 1^7-56) should prompt referral to specialists for assessment.

Continue to: In the emergency department...

In the emergency department and academic hospitals, key investigations can identify causes of imbalance:

• Electrocardiography and Holter monitoring test for cardiac arrhythmias.
• Echocardiography identifies structural abnormalities.
• Radiography and computed tomography are useful for detecting musculoskeletal abnormalities.
• Bone densitometry can identify osteoporosis.
• Head and spinal cord magnetic resonance imaging can be used to identify lesions of the central nervous system.
• Computed tomographic angiography of the head and neck is useful for identifying stroke, cerebral atrophy, and stenotic lesions of the carotid and vertebral arteries.
• Nerve conduction studies and levels of serum vitamin B₁₂, hemoglobin A1C, thyroid-stimulating hormone, and random cortisol can uncover causes of peripheral neuropathy.
• Bedside cognitive screening tests can be used to measure cognitive decline.⁷²
• Suspicion of vestibular disease requires audiometry and vestibular testing, including videonystagmography, head impulse testing, and vestibular evoked myogenic potentials.

In many cases of imbalance, no specific underlying correctable cause is discovered.

Management of imbalance

Pharmacotherapy

Targeted pharmacotherapy can be utilized in select clinical scenarios:

• Medical treatment of peripheral neuropathy should target the underlying condition.
• Cognitive behavioral therapy and antidepressants are useful for treating anxiety and depressive disorders.⁷³
• Musculoskeletal pain can be managed with acetaminophen and topical nonsteroidal anti-inflammatory drugs (NSAIDs), using a short course of an oral NSAID when needed.⁷⁴
• Cardiovascular disease management might include any of several classes of pharmacotherapy, including antiplatelet and lipid-lowering medications, antiarrhythmic drugs, and antihypertensive agents.
• Acute episodes of vertigo due to vestibular neuritis or labyrinthitis can be managed with an antiemetic.⁴⁶

Surgical treatment

Surgery is infrequently considered for patients with imbalance. Examples of indications include microsurgical resection of vestibular schwannoma, resection of central nervous system tumors, lens replacement surgery for cataract, surgical management of severe spinal fracture, and hip or knee arthroplasty in select patients.

Tools for assessing the risk of falls

Scoring systems called falls risk assessment tools, or FRAT, have been developed to gauge a patient’s risk of falling. The various FRATs differ in specificity and sensitivity for predicting the risk of falls, and are typically designed for specific clinical environments, such as hospital inpatient care or long-term care facilities. Specifically, FRATs attempt to classify risk using sets of risk factors known to be associated with falls.

Continue to: Research abounds into...

In our experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system.

Research abounds into the validity of commonly used FRATs across institutions, patient populations, and clinical environments:

The Johns Hopkins FRAT^a determines risk using metrics such as age, fall history, incontinence, cognition, mobility, and medications⁷⁵; it is predominantly used for assessment in hospital inpatient units. This tool has been validated repeatedly.^76,77

Peninsula Health FRAT^b stratifies patients in subacute and residential aged-care settings, based on risk factors that include recent falls, medications, psychological status, and cognition.⁷⁸

FRAT-up^c is a web-based tool that generates falls risk using risk factors that users input. This tool has been studied in the context of patients older than 65 years living in the community.⁷⁹

Although FRATs are reasonably useful for predicting falls, their utility varies by patient population and clinical context. Moreover, it has been suggested that FRATs neglect environmental and personal factors when assessing risk by focusing primarily on bodily factors.⁸⁰ Implementing a FRAT requires extensive consideration of the target population and should be accompanied by clinical judgment that is grounded in an individual patient’s circumstances.⁸¹

Continue to: Preventing falls in primary care

 

 

Preventing falls in primary care

An approach to preventing falls includes the development of individualized programs that account for frailty, a syndrome of physiologic decline associated with aging. Because frailty leads to diminished balance and mobility, a patient’s frailty index—determined using the 5 frailty phenotype criteria (exhaustion, weight loss, low physical activity, weakness, slowness)⁸² or the Canadian Study of Health and Aging Clinical Frailty Scale⁸³—is a useful tool for predicting falls risk and readmission for falls following trauma-related injury. Prevention of falls in communities is critical for reducing mortality and allowing older people to maintain their independence and quality of life.

Exercise. In some areas, exercise and falls prevention programs are accessible to seniors.⁸⁴ Community exercise programs that focus on balance retraining and muscle strengthening can reduce the risk of falls.^73,85 The Choosing Wisely initiative of the ABIM [American Board of Internal Medicine] Foundation recommends that exercise programs be designed around an accurate functional baseline of the patient to avoid underdosed strength training.⁵⁴

Multifactorial risk assessment in high-risk patients can reduce the rate of falls. Such an assessment includes examination of orthostatic blood pressure, vision and hearing, bone health, gait, activities of daily living, cognition, and environmental hazards, and enables provision of necessary interventions.^73,86 Hearing amplification, specifically, correlates with enhanced postural control, slowed cognitive decline, and a reduced likelihood of falls.^87-93 The mechanism behind improved balance performance might be reduced cognitive load through supporting a patient’s listening needs.^88-90

Pharmacotherapy. Optimizing medications and performing a complete medication review before prescribing new medications is highly recommended to avoid unnecessary polypharmacy^7,8,18,53-56 (TABLE 1^7-56).

Management of comorbidities associated with a higher risk of falls, including arthritis, cancer, stroke, diabetes, depression, kidney disease, chronic obstructive pulmonary disease, cognitive impairment, hypertension, and atrial fibrillation, is essential.^94-96

Continue to: Home safety interventions

Home safety interventions, through occupational therapy, are important. These include removing unsafe mats and step-overs and installing nonslip strips on stairs, ­double-sided tape under mats, and handrails.^73-97

Screening for risk of falls. The Centers for Disease Control and Prevention recommends that (1) all patients older than 65 years and (2) any patient presenting with an acute fall undergo screening for their risk of falls.⁹⁸ When a patient is identified as at risk of falling, you can, when appropriate, assess modifiable risk factors and facilitate interventions.⁹⁸ This strategy is supported by a 2018 statement from the US Preventive Services Task Force⁹⁹ that recommends identifying high-risk patients who have:

• a history of falling
• a balance disturbance that causes a deficit of mobility or function
• poor performance on clinical tests, such as the 3-meter Timed Up and Go (TUG) assessment (www.cdc.gov/steadi/pdf/TUG_test-print.pdf).

In addition to visual, proprioception, and vestibular dysfunction, cognitive and neurologic decline are also factors in imbalance.

An increased risk of falls should prompt you to refer the patient to community programs and physiotherapy in accordance with the individual’s personal goals⁹⁹; a balance and vestibular physiotherapist is ideally positioned to accurately assess and manage patients at risk of falls. Specifically, the Task Force identified exercise programs and multifactorial interventions as being beneficial in preventing falls in high-risk older people.⁹⁹

Balance assessment and rehabilitation in specialty centers

Polypharmacy— typically, defined as taking 4 or more medications— has been repeatedly associated with a heightened risk of falls.

An individualized rehabilitation program aims to restore safe mobility by testing and addressing specific balance deficits, improving functional balance, and increasing balance confidence. Collaboration with colleagues from physiotherapy and occupational therapy aids in tailoring individualized programs.

Many tests are available to assess balance, determine the risk of falls, and guide rehabilitation:

• The timed 10-meter walk test^d and the TUG test are simple assessments that measure functional mobility; both have normalized values for the risk of falls. A TUG time of ≥ 12 seconds suggests a high risk of falls.
• The 30-second chair stand^e evaluates functional lower-extremity strength in older patients. The test can indicate if lower-extremity strength is contributing to a patient’s imbalance.
• The modified clinical test of sensory interaction in balance^f is a static balance test that measures the integrity of sensory inputs. The test can suggest if 1 or more sensory systems are compromised.
• The mini balance evaluation systems test^g is similar: It can differentiate balance deficits by underlying system and allows individualization of a rehabilitation program.
• The functional gait assessment^h is a modification of the dynamic gait index that assesses postural stability during everyday dynamic activities, including tasks such as walking with head turns and pivots.
• The Berg Balance Scaleⁱ continues to be used extensively to assess balance.

Continue to: The mini balance evaluation systems test...

All patients older than 65 years and any patient presenting with an acute fall should undergo screening for their risk of falls.

The mini balance evaluation systems test, functional gait index, and Berg Balance Scale all have normative age-graded values to predict fall risk.

CASE

Mr. J was referred for balance assessment and to a rehabilitation program. He underwent balance physiotherapy, including multifactorial balance assessment, joined a community exercise program, was fitted with hearing aids, and had his home environment optimized by an occupational therapist. (See examples of “home safety interventions” under “Preventing falls in primary care.”)

Exercise programs should be designed around an accurate functional baseline of the patient to avoid underdosed strength training.

3 months later. Mr. J says he feels stronger on his feet. His knee pain has eased, and he is more confident walking around his home. He continues to engage in exercise programs and is comfortable running errands with his spouse.

CORRESPONDENCE
Jason A. Beyea, MD, PhD, FRCSC, Division of OtolaryngologyHead and Neck Surgery, Queen’s University, 144 Brock Street, Kingston, Ontario, Canada, K7L 5G2; jason.beyea@queensu.ca

^a www.hopkinsmedicine.org/institute_nursing/models_tools/jhfrat_acute%20care%20original_6_22_17.pdf

^b https://content.health.vic.gov.au/sites/default/files/migrated/files/collections/policies-and-guidelines/b/b2b_1a_frat_pdf.pdf

^c www.ncbi.nlm.nih.gov/pmc/articles/PMC4376110/figure/figure14/?report=objectonly

^d www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/core-measure-10-meter-walk-test-(10mwt)_final.pdf?sfvrsn=c5585243_2&sfvrsn =c5585243_2

^e www.cdc.gov/steadi/pdf/STEADI-Assessment-30Sec-508.pdf

^f www.mdapp.co/mctsib-modified-clinical-test-of-sensory-interaction-in-balance-calculator-404/

^g www.sralab.org/sites/default/files/2017-07/MiniBEST_revised_final_3_8_13.pdf

^h www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/function-gait-assessment-pocket-guide-proof9-(2).pdf?sfvrsn=b4f35043_0

ⁱ www.ncbi.nlm.nih.gov/books/NBK574518/

CASE Mr. J, a 75-year-old man, presents to your family practice reporting that he feels increasingly unsteady and slow while walking. He fell twice last year, without resulting injury. He now worries about tripping while walking around the house and relies on his spouse to run errands.

Almost 30% of people older than 65 years report 1 or more falls annually.

Clearly, Mr. J is experiencing a problem with balance. What management approach should you undertake to prevent him from falling?

Copyright Scott Bodell

Balance disorders are common in older people and drastically hinder quality of life.^1-4 Patients often describe imbalance as vague symptoms: dizziness, unsteadiness, faintness, spinning sensations.^5,6 Importantly, balance disorders disrupt normal gait and contribute to falls that are a major cause of disability and morbidity in older people. Almost 30% of people older than 65 years report 1 or more falls annually.⁷ Factors that increase the risk of falls include impaired mobility, previously reported falls, reduced psychological functioning, chronic medical conditions, and polypharmacy.^7,8

The cause of any single case of imbalance is often multifactorial, resulting from dysfunction of multiple body systems (TABLE 1^7-56); in our clinical experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system. These alterations in function arise in 3 key systems—vision, proprioception, and vestibular function—which signal to, and are incorporated by, the cerebellum to mediate balance. Cognitive and neurologic decline are also factors in imbalance.

Considering that 20% of falls result in serious injury in older populations, it is important to identify balance disorders and implement preventive strategies to mitigate harmful consequences of falls on patients’ health and independence.^7,57 In this article, we answer the question that the case presentation raises about the proper management approach to imbalance in family practice, including assessment of risk and rehabilitation strategies to reduce the risk of falls. Our insights and recommendations are based on our clinical experience and a review of the medical literature from the past 40 years.

CASE Mr. J has a history of hypertension, age-­related hearing loss, and osteoarthritis of the knees; he has not had surgery for the arthritis. His medications are antihypertensives and extra-strength acetaminophen for knee pain.

Making the diagnosis of a balance disorder

History

A thorough clinical history, often including a collateral history from caregivers, narrows the differential diagnosis. Information regarding onset, duration, timing, character, and previous episodes of imbalance is essential. Symptoms of imbalance are often challenging for the patient to describe: They might use terms such as vertigo or dizziness, when, in fact, on further questioning, they are describing balance difficulties. Inquiry into (1) their use of assistive walking devices and (2) development or exacerbation of neurologic, musculoskeletal, auditory, visual, and mood symptoms is necessary. Note the current level of their mobility, episodes of pain or fatigue, previous falls and associated injuries, fear of falling, balance confidence, and sensations that precede falls.⁵⁸

Continue to: The medical and surgical histories

The medical and surgical histories are key pieces of information. The history of smoking, alcohol habits, and substance use is relevant.

A robust medication history is essential to evaluate a patient’s risk of falling. Polypharmacy—typically, defined as taking 4 or more medications—has been repeatedly associated with a heightened risk of falls.^53,59-61 Moreover, a dose-dependent association between polypharmacy and hospitalization following falls has been identified, and demonstrates that taking 10 or more medications greatly increases the risk of hospitalization.⁵⁹ Studies of polypharmacy cement the importance of inquiring about medication use when assessing imbalance, particularly in older patients.

Physical examination

A focused and detailed physical examination provides insight into systems that should be investigated:

• Obtain vital signs, including orthostatic vitals to test for orthostatic hypotension⁶²; keep in mind that symptoms of orthostatic dizziness can occur without orthostatic hypotension.
• Examine gait, which can distinguish between causes of imbalance (TABLE 2).^21,40,63-70
• Perform a cardiac examination.
• Assess visual acuity and visual fields; test for nystagmus and identify any optic-nerve and retinal abnormalities.
• Evaluate lower-limb sensation, proprioception, and motor function.
• Evaluate suspected vestibular dysfunction, including dysfunction with positional testing (the Dix-Hallpike maneuver⁷¹). The patient is taken from sitting to supine while the head is rotated 45° to the tested side by the examiner. As the patient moves into a supine position, the neck is extended 30° off the table and held for at least 30 seconds. The maneuver is positive if torsional nystagmus is noted while the head is held rotated during neck extension. The maneuver is negative if the patient reports dizziness, vertigo, unsteadiness, or “pressure in the head.” Torsional nystagmus must be present to confirm a diagnosis of benign paroxysmal positional vertigo.
• If you suspect a central nervous system cause of imbalance, assess the cranial nerves, coordination, strength, and, of course, balance.

CASE

Mr. J’s physical examination showed normal vital signs without significant postural changes in blood pressure. Gait analysis revealed a slowed gait, with reduced range of motion in both knees over the entire gait cycle. Audiometry revealed symmetric moderate sensorineural hearing loss characteristic of presbycusis.

Diagnostic investigations

Consider focused investigations into imbalance based on the history and physical examination. We discourage overly broad testing and imaging; in primary care, cost and limited access to technology can bar robust investigations into causes of imbalance. However, identification of acute pathologies should prompt immediate referral to the emergency department. Furthermore, specific symptoms (TABLE 1^7-56) should prompt referral to specialists for assessment.

Continue to: In the emergency department...

In the emergency department and academic hospitals, key investigations can identify causes of imbalance:

• Electrocardiography and Holter monitoring test for cardiac arrhythmias.
• Echocardiography identifies structural abnormalities.
• Radiography and computed tomography are useful for detecting musculoskeletal abnormalities.
• Bone densitometry can identify osteoporosis.
• Head and spinal cord magnetic resonance imaging can be used to identify lesions of the central nervous system.
• Computed tomographic angiography of the head and neck is useful for identifying stroke, cerebral atrophy, and stenotic lesions of the carotid and vertebral arteries.
• Nerve conduction studies and levels of serum vitamin B₁₂, hemoglobin A1C, thyroid-stimulating hormone, and random cortisol can uncover causes of peripheral neuropathy.
• Bedside cognitive screening tests can be used to measure cognitive decline.⁷²
• Suspicion of vestibular disease requires audiometry and vestibular testing, including videonystagmography, head impulse testing, and vestibular evoked myogenic potentials.

In many cases of imbalance, no specific underlying correctable cause is discovered.

Management of imbalance

Pharmacotherapy

Targeted pharmacotherapy can be utilized in select clinical scenarios:

• Medical treatment of peripheral neuropathy should target the underlying condition.
• Cognitive behavioral therapy and antidepressants are useful for treating anxiety and depressive disorders.⁷³
• Musculoskeletal pain can be managed with acetaminophen and topical nonsteroidal anti-inflammatory drugs (NSAIDs), using a short course of an oral NSAID when needed.⁷⁴
• Cardiovascular disease management might include any of several classes of pharmacotherapy, including antiplatelet and lipid-lowering medications, antiarrhythmic drugs, and antihypertensive agents.
• Acute episodes of vertigo due to vestibular neuritis or labyrinthitis can be managed with an antiemetic.⁴⁶

Surgical treatment

Surgery is infrequently considered for patients with imbalance. Examples of indications include microsurgical resection of vestibular schwannoma, resection of central nervous system tumors, lens replacement surgery for cataract, surgical management of severe spinal fracture, and hip or knee arthroplasty in select patients.

Tools for assessing the risk of falls

Scoring systems called falls risk assessment tools, or FRAT, have been developed to gauge a patient’s risk of falling. The various FRATs differ in specificity and sensitivity for predicting the risk of falls, and are typically designed for specific clinical environments, such as hospital inpatient care or long-term care facilities. Specifically, FRATs attempt to classify risk using sets of risk factors known to be associated with falls.

Continue to: Research abounds into...

In our experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system.

Research abounds into the validity of commonly used FRATs across institutions, patient populations, and clinical environments:

The Johns Hopkins FRAT^a determines risk using metrics such as age, fall history, incontinence, cognition, mobility, and medications⁷⁵; it is predominantly used for assessment in hospital inpatient units. This tool has been validated repeatedly.^76,77

Peninsula Health FRAT^b stratifies patients in subacute and residential aged-care settings, based on risk factors that include recent falls, medications, psychological status, and cognition.⁷⁸

FRAT-up^c is a web-based tool that generates falls risk using risk factors that users input. This tool has been studied in the context of patients older than 65 years living in the community.⁷⁹

Although FRATs are reasonably useful for predicting falls, their utility varies by patient population and clinical context. Moreover, it has been suggested that FRATs neglect environmental and personal factors when assessing risk by focusing primarily on bodily factors.⁸⁰ Implementing a FRAT requires extensive consideration of the target population and should be accompanied by clinical judgment that is grounded in an individual patient’s circumstances.⁸¹

Continue to: Preventing falls in primary care

 

 

Preventing falls in primary care

An approach to preventing falls includes the development of individualized programs that account for frailty, a syndrome of physiologic decline associated with aging. Because frailty leads to diminished balance and mobility, a patient’s frailty index—determined using the 5 frailty phenotype criteria (exhaustion, weight loss, low physical activity, weakness, slowness)⁸² or the Canadian Study of Health and Aging Clinical Frailty Scale⁸³—is a useful tool for predicting falls risk and readmission for falls following trauma-related injury. Prevention of falls in communities is critical for reducing mortality and allowing older people to maintain their independence and quality of life.

Exercise. In some areas, exercise and falls prevention programs are accessible to seniors.⁸⁴ Community exercise programs that focus on balance retraining and muscle strengthening can reduce the risk of falls.^73,85 The Choosing Wisely initiative of the ABIM [American Board of Internal Medicine] Foundation recommends that exercise programs be designed around an accurate functional baseline of the patient to avoid underdosed strength training.⁵⁴

Multifactorial risk assessment in high-risk patients can reduce the rate of falls. Such an assessment includes examination of orthostatic blood pressure, vision and hearing, bone health, gait, activities of daily living, cognition, and environmental hazards, and enables provision of necessary interventions.^73,86 Hearing amplification, specifically, correlates with enhanced postural control, slowed cognitive decline, and a reduced likelihood of falls.^87-93 The mechanism behind improved balance performance might be reduced cognitive load through supporting a patient’s listening needs.^88-90

Pharmacotherapy. Optimizing medications and performing a complete medication review before prescribing new medications is highly recommended to avoid unnecessary polypharmacy^7,8,18,53-56 (TABLE 1^7-56).

Management of comorbidities associated with a higher risk of falls, including arthritis, cancer, stroke, diabetes, depression, kidney disease, chronic obstructive pulmonary disease, cognitive impairment, hypertension, and atrial fibrillation, is essential.^94-96

Continue to: Home safety interventions

Home safety interventions, through occupational therapy, are important. These include removing unsafe mats and step-overs and installing nonslip strips on stairs, ­double-sided tape under mats, and handrails.^73-97

Screening for risk of falls. The Centers for Disease Control and Prevention recommends that (1) all patients older than 65 years and (2) any patient presenting with an acute fall undergo screening for their risk of falls.⁹⁸ When a patient is identified as at risk of falling, you can, when appropriate, assess modifiable risk factors and facilitate interventions.⁹⁸ This strategy is supported by a 2018 statement from the US Preventive Services Task Force⁹⁹ that recommends identifying high-risk patients who have:

• a history of falling
• a balance disturbance that causes a deficit of mobility or function
• poor performance on clinical tests, such as the 3-meter Timed Up and Go (TUG) assessment (www.cdc.gov/steadi/pdf/TUG_test-print.pdf).

In addition to visual, proprioception, and vestibular dysfunction, cognitive and neurologic decline are also factors in imbalance.

An increased risk of falls should prompt you to refer the patient to community programs and physiotherapy in accordance with the individual’s personal goals⁹⁹; a balance and vestibular physiotherapist is ideally positioned to accurately assess and manage patients at risk of falls. Specifically, the Task Force identified exercise programs and multifactorial interventions as being beneficial in preventing falls in high-risk older people.⁹⁹

Balance assessment and rehabilitation in specialty centers

Polypharmacy— typically, defined as taking 4 or more medications— has been repeatedly associated with a heightened risk of falls.

An individualized rehabilitation program aims to restore safe mobility by testing and addressing specific balance deficits, improving functional balance, and increasing balance confidence. Collaboration with colleagues from physiotherapy and occupational therapy aids in tailoring individualized programs.

Many tests are available to assess balance, determine the risk of falls, and guide rehabilitation:

• The timed 10-meter walk test^d and the TUG test are simple assessments that measure functional mobility; both have normalized values for the risk of falls. A TUG time of ≥ 12 seconds suggests a high risk of falls.
• The 30-second chair stand^e evaluates functional lower-extremity strength in older patients. The test can indicate if lower-extremity strength is contributing to a patient’s imbalance.
• The modified clinical test of sensory interaction in balance^f is a static balance test that measures the integrity of sensory inputs. The test can suggest if 1 or more sensory systems are compromised.
• The mini balance evaluation systems test^g is similar: It can differentiate balance deficits by underlying system and allows individualization of a rehabilitation program.
• The functional gait assessment^h is a modification of the dynamic gait index that assesses postural stability during everyday dynamic activities, including tasks such as walking with head turns and pivots.
• The Berg Balance Scaleⁱ continues to be used extensively to assess balance.

Continue to: The mini balance evaluation systems test...

All patients older than 65 years and any patient presenting with an acute fall should undergo screening for their risk of falls.

The mini balance evaluation systems test, functional gait index, and Berg Balance Scale all have normative age-graded values to predict fall risk.

CASE

Mr. J was referred for balance assessment and to a rehabilitation program. He underwent balance physiotherapy, including multifactorial balance assessment, joined a community exercise program, was fitted with hearing aids, and had his home environment optimized by an occupational therapist. (See examples of “home safety interventions” under “Preventing falls in primary care.”)

Exercise programs should be designed around an accurate functional baseline of the patient to avoid underdosed strength training.

3 months later. Mr. J says he feels stronger on his feet. His knee pain has eased, and he is more confident walking around his home. He continues to engage in exercise programs and is comfortable running errands with his spouse.

CORRESPONDENCE
Jason A. Beyea, MD, PhD, FRCSC, Division of OtolaryngologyHead and Neck Surgery, Queen’s University, 144 Brock Street, Kingston, Ontario, Canada, K7L 5G2; jason.beyea@queensu.ca

^a www.hopkinsmedicine.org/institute_nursing/models_tools/jhfrat_acute%20care%20original_6_22_17.pdf

^b https://content.health.vic.gov.au/sites/default/files/migrated/files/collections/policies-and-guidelines/b/b2b_1a_frat_pdf.pdf

^c www.ncbi.nlm.nih.gov/pmc/articles/PMC4376110/figure/figure14/?report=objectonly

^d www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/core-measure-10-meter-walk-test-(10mwt)_final.pdf?sfvrsn=c5585243_2&sfvrsn =c5585243_2

^e www.cdc.gov/steadi/pdf/STEADI-Assessment-30Sec-508.pdf

^f www.mdapp.co/mctsib-modified-clinical-test-of-sensory-interaction-in-balance-calculator-404/

^g www.sralab.org/sites/default/files/2017-07/MiniBEST_revised_final_3_8_13.pdf

^h www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/function-gait-assessment-pocket-guide-proof9-(2).pdf?sfvrsn=b4f35043_0

ⁱ www.ncbi.nlm.nih.gov/books/NBK574518/

CASE Mr. J, a 75-year-old man, presents to your family practice reporting that he feels increasingly unsteady and slow while walking. He fell twice last year, without resulting injury. He now worries about tripping while walking around the house and relies on his spouse to run errands.

Almost 30% of people older than 65 years report 1 or more falls annually.

Clearly, Mr. J is experiencing a problem with balance. What management approach should you undertake to prevent him from falling?

Copyright Scott Bodell

Balance disorders are common in older people and drastically hinder quality of life.^1-4 Patients often describe imbalance as vague symptoms: dizziness, unsteadiness, faintness, spinning sensations.^5,6 Importantly, balance disorders disrupt normal gait and contribute to falls that are a major cause of disability and morbidity in older people. Almost 30% of people older than 65 years report 1 or more falls annually.⁷ Factors that increase the risk of falls include impaired mobility, previously reported falls, reduced psychological functioning, chronic medical conditions, and polypharmacy.^7,8

The cause of any single case of imbalance is often multifactorial, resulting from dysfunction of multiple body systems (TABLE 1^7-56); in our clinical experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system. These alterations in function arise in 3 key systems—vision, proprioception, and vestibular function—which signal to, and are incorporated by, the cerebellum to mediate balance. Cognitive and neurologic decline are also factors in imbalance.

Considering that 20% of falls result in serious injury in older populations, it is important to identify balance disorders and implement preventive strategies to mitigate harmful consequences of falls on patients’ health and independence.^7,57 In this article, we answer the question that the case presentation raises about the proper management approach to imbalance in family practice, including assessment of risk and rehabilitation strategies to reduce the risk of falls. Our insights and recommendations are based on our clinical experience and a review of the medical literature from the past 40 years.

CASE Mr. J has a history of hypertension, age-­related hearing loss, and osteoarthritis of the knees; he has not had surgery for the arthritis. His medications are antihypertensives and extra-strength acetaminophen for knee pain.

Making the diagnosis of a balance disorder

History

A thorough clinical history, often including a collateral history from caregivers, narrows the differential diagnosis. Information regarding onset, duration, timing, character, and previous episodes of imbalance is essential. Symptoms of imbalance are often challenging for the patient to describe: They might use terms such as vertigo or dizziness, when, in fact, on further questioning, they are describing balance difficulties. Inquiry into (1) their use of assistive walking devices and (2) development or exacerbation of neurologic, musculoskeletal, auditory, visual, and mood symptoms is necessary. Note the current level of their mobility, episodes of pain or fatigue, previous falls and associated injuries, fear of falling, balance confidence, and sensations that precede falls.⁵⁸

Continue to: The medical and surgical histories

The medical and surgical histories are key pieces of information. The history of smoking, alcohol habits, and substance use is relevant.

A robust medication history is essential to evaluate a patient’s risk of falling. Polypharmacy—typically, defined as taking 4 or more medications—has been repeatedly associated with a heightened risk of falls.^53,59-61 Moreover, a dose-dependent association between polypharmacy and hospitalization following falls has been identified, and demonstrates that taking 10 or more medications greatly increases the risk of hospitalization.⁵⁹ Studies of polypharmacy cement the importance of inquiring about medication use when assessing imbalance, particularly in older patients.

Physical examination

A focused and detailed physical examination provides insight into systems that should be investigated:

• Obtain vital signs, including orthostatic vitals to test for orthostatic hypotension⁶²; keep in mind that symptoms of orthostatic dizziness can occur without orthostatic hypotension.
• Examine gait, which can distinguish between causes of imbalance (TABLE 2).^21,40,63-70
• Perform a cardiac examination.
• Assess visual acuity and visual fields; test for nystagmus and identify any optic-nerve and retinal abnormalities.
• Evaluate lower-limb sensation, proprioception, and motor function.
• Evaluate suspected vestibular dysfunction, including dysfunction with positional testing (the Dix-Hallpike maneuver⁷¹). The patient is taken from sitting to supine while the head is rotated 45° to the tested side by the examiner. As the patient moves into a supine position, the neck is extended 30° off the table and held for at least 30 seconds. The maneuver is positive if torsional nystagmus is noted while the head is held rotated during neck extension. The maneuver is negative if the patient reports dizziness, vertigo, unsteadiness, or “pressure in the head.” Torsional nystagmus must be present to confirm a diagnosis of benign paroxysmal positional vertigo.
• If you suspect a central nervous system cause of imbalance, assess the cranial nerves, coordination, strength, and, of course, balance.

CASE

Mr. J’s physical examination showed normal vital signs without significant postural changes in blood pressure. Gait analysis revealed a slowed gait, with reduced range of motion in both knees over the entire gait cycle. Audiometry revealed symmetric moderate sensorineural hearing loss characteristic of presbycusis.

Diagnostic investigations

Consider focused investigations into imbalance based on the history and physical examination. We discourage overly broad testing and imaging; in primary care, cost and limited access to technology can bar robust investigations into causes of imbalance. However, identification of acute pathologies should prompt immediate referral to the emergency department. Furthermore, specific symptoms (TABLE 1^7-56) should prompt referral to specialists for assessment.

Continue to: In the emergency department...

In the emergency department and academic hospitals, key investigations can identify causes of imbalance:

• Electrocardiography and Holter monitoring test for cardiac arrhythmias.
• Echocardiography identifies structural abnormalities.
• Radiography and computed tomography are useful for detecting musculoskeletal abnormalities.
• Bone densitometry can identify osteoporosis.
• Head and spinal cord magnetic resonance imaging can be used to identify lesions of the central nervous system.
• Computed tomographic angiography of the head and neck is useful for identifying stroke, cerebral atrophy, and stenotic lesions of the carotid and vertebral arteries.
• Nerve conduction studies and levels of serum vitamin B₁₂, hemoglobin A1C, thyroid-stimulating hormone, and random cortisol can uncover causes of peripheral neuropathy.
• Bedside cognitive screening tests can be used to measure cognitive decline.⁷²
• Suspicion of vestibular disease requires audiometry and vestibular testing, including videonystagmography, head impulse testing, and vestibular evoked myogenic potentials.

In many cases of imbalance, no specific underlying correctable cause is discovered.

Management of imbalance

Pharmacotherapy

Targeted pharmacotherapy can be utilized in select clinical scenarios:

• Medical treatment of peripheral neuropathy should target the underlying condition.
• Cognitive behavioral therapy and antidepressants are useful for treating anxiety and depressive disorders.⁷³
• Musculoskeletal pain can be managed with acetaminophen and topical nonsteroidal anti-inflammatory drugs (NSAIDs), using a short course of an oral NSAID when needed.⁷⁴
• Cardiovascular disease management might include any of several classes of pharmacotherapy, including antiplatelet and lipid-lowering medications, antiarrhythmic drugs, and antihypertensive agents.
• Acute episodes of vertigo due to vestibular neuritis or labyrinthitis can be managed with an antiemetic.⁴⁶

Surgical treatment

Surgery is infrequently considered for patients with imbalance. Examples of indications include microsurgical resection of vestibular schwannoma, resection of central nervous system tumors, lens replacement surgery for cataract, surgical management of severe spinal fracture, and hip or knee arthroplasty in select patients.

Tools for assessing the risk of falls

Scoring systems called falls risk assessment tools, or FRAT, have been developed to gauge a patient’s risk of falling. The various FRATs differ in specificity and sensitivity for predicting the risk of falls, and are typically designed for specific clinical environments, such as hospital inpatient care or long-term care facilities. Specifically, FRATs attempt to classify risk using sets of risk factors known to be associated with falls.

Continue to: Research abounds into...

In our experience, most patients with imbalance and who are at risk of falls do not have a detectable deficit of the vestibular system.

Research abounds into the validity of commonly used FRATs across institutions, patient populations, and clinical environments:

The Johns Hopkins FRAT^a determines risk using metrics such as age, fall history, incontinence, cognition, mobility, and medications⁷⁵; it is predominantly used for assessment in hospital inpatient units. This tool has been validated repeatedly.^76,77

Peninsula Health FRAT^b stratifies patients in subacute and residential aged-care settings, based on risk factors that include recent falls, medications, psychological status, and cognition.⁷⁸

FRAT-up^c is a web-based tool that generates falls risk using risk factors that users input. This tool has been studied in the context of patients older than 65 years living in the community.⁷⁹

Although FRATs are reasonably useful for predicting falls, their utility varies by patient population and clinical context. Moreover, it has been suggested that FRATs neglect environmental and personal factors when assessing risk by focusing primarily on bodily factors.⁸⁰ Implementing a FRAT requires extensive consideration of the target population and should be accompanied by clinical judgment that is grounded in an individual patient’s circumstances.⁸¹

Continue to: Preventing falls in primary care

 

 

Preventing falls in primary care

An approach to preventing falls includes the development of individualized programs that account for frailty, a syndrome of physiologic decline associated with aging. Because frailty leads to diminished balance and mobility, a patient’s frailty index—determined using the 5 frailty phenotype criteria (exhaustion, weight loss, low physical activity, weakness, slowness)⁸² or the Canadian Study of Health and Aging Clinical Frailty Scale⁸³—is a useful tool for predicting falls risk and readmission for falls following trauma-related injury. Prevention of falls in communities is critical for reducing mortality and allowing older people to maintain their independence and quality of life.

Exercise. In some areas, exercise and falls prevention programs are accessible to seniors.⁸⁴ Community exercise programs that focus on balance retraining and muscle strengthening can reduce the risk of falls.^73,85 The Choosing Wisely initiative of the ABIM [American Board of Internal Medicine] Foundation recommends that exercise programs be designed around an accurate functional baseline of the patient to avoid underdosed strength training.⁵⁴

Multifactorial risk assessment in high-risk patients can reduce the rate of falls. Such an assessment includes examination of orthostatic blood pressure, vision and hearing, bone health, gait, activities of daily living, cognition, and environmental hazards, and enables provision of necessary interventions.^73,86 Hearing amplification, specifically, correlates with enhanced postural control, slowed cognitive decline, and a reduced likelihood of falls.^87-93 The mechanism behind improved balance performance might be reduced cognitive load through supporting a patient’s listening needs.^88-90

Pharmacotherapy. Optimizing medications and performing a complete medication review before prescribing new medications is highly recommended to avoid unnecessary polypharmacy^7,8,18,53-56 (TABLE 1^7-56).

Management of comorbidities associated with a higher risk of falls, including arthritis, cancer, stroke, diabetes, depression, kidney disease, chronic obstructive pulmonary disease, cognitive impairment, hypertension, and atrial fibrillation, is essential.^94-96

Continue to: Home safety interventions

Home safety interventions, through occupational therapy, are important. These include removing unsafe mats and step-overs and installing nonslip strips on stairs, ­double-sided tape under mats, and handrails.^73-97

Screening for risk of falls. The Centers for Disease Control and Prevention recommends that (1) all patients older than 65 years and (2) any patient presenting with an acute fall undergo screening for their risk of falls.⁹⁸ When a patient is identified as at risk of falling, you can, when appropriate, assess modifiable risk factors and facilitate interventions.⁹⁸ This strategy is supported by a 2018 statement from the US Preventive Services Task Force⁹⁹ that recommends identifying high-risk patients who have:

• a history of falling
• a balance disturbance that causes a deficit of mobility or function
• poor performance on clinical tests, such as the 3-meter Timed Up and Go (TUG) assessment (www.cdc.gov/steadi/pdf/TUG_test-print.pdf).

In addition to visual, proprioception, and vestibular dysfunction, cognitive and neurologic decline are also factors in imbalance.

An increased risk of falls should prompt you to refer the patient to community programs and physiotherapy in accordance with the individual’s personal goals⁹⁹; a balance and vestibular physiotherapist is ideally positioned to accurately assess and manage patients at risk of falls. Specifically, the Task Force identified exercise programs and multifactorial interventions as being beneficial in preventing falls in high-risk older people.⁹⁹

Balance assessment and rehabilitation in specialty centers

Polypharmacy— typically, defined as taking 4 or more medications— has been repeatedly associated with a heightened risk of falls.

An individualized rehabilitation program aims to restore safe mobility by testing and addressing specific balance deficits, improving functional balance, and increasing balance confidence. Collaboration with colleagues from physiotherapy and occupational therapy aids in tailoring individualized programs.

Many tests are available to assess balance, determine the risk of falls, and guide rehabilitation:

• The timed 10-meter walk test^d and the TUG test are simple assessments that measure functional mobility; both have normalized values for the risk of falls. A TUG time of ≥ 12 seconds suggests a high risk of falls.
• The 30-second chair stand^e evaluates functional lower-extremity strength in older patients. The test can indicate if lower-extremity strength is contributing to a patient’s imbalance.
• The modified clinical test of sensory interaction in balance^f is a static balance test that measures the integrity of sensory inputs. The test can suggest if 1 or more sensory systems are compromised.
• The mini balance evaluation systems test^g is similar: It can differentiate balance deficits by underlying system and allows individualization of a rehabilitation program.
• The functional gait assessment^h is a modification of the dynamic gait index that assesses postural stability during everyday dynamic activities, including tasks such as walking with head turns and pivots.
• The Berg Balance Scaleⁱ continues to be used extensively to assess balance.

Continue to: The mini balance evaluation systems test...

All patients older than 65 years and any patient presenting with an acute fall should undergo screening for their risk of falls.

The mini balance evaluation systems test, functional gait index, and Berg Balance Scale all have normative age-graded values to predict fall risk.

CASE

Mr. J was referred for balance assessment and to a rehabilitation program. He underwent balance physiotherapy, including multifactorial balance assessment, joined a community exercise program, was fitted with hearing aids, and had his home environment optimized by an occupational therapist. (See examples of “home safety interventions” under “Preventing falls in primary care.”)

Exercise programs should be designed around an accurate functional baseline of the patient to avoid underdosed strength training.

3 months later. Mr. J says he feels stronger on his feet. His knee pain has eased, and he is more confident walking around his home. He continues to engage in exercise programs and is comfortable running errands with his spouse.

CORRESPONDENCE
Jason A. Beyea, MD, PhD, FRCSC, Division of OtolaryngologyHead and Neck Surgery, Queen’s University, 144 Brock Street, Kingston, Ontario, Canada, K7L 5G2; jason.beyea@queensu.ca

^a www.hopkinsmedicine.org/institute_nursing/models_tools/jhfrat_acute%20care%20original_6_22_17.pdf

^b https://content.health.vic.gov.au/sites/default/files/migrated/files/collections/policies-and-guidelines/b/b2b_1a_frat_pdf.pdf

^c www.ncbi.nlm.nih.gov/pmc/articles/PMC4376110/figure/figure14/?report=objectonly

^d www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/core-measure-10-meter-walk-test-(10mwt)_final.pdf?sfvrsn=c5585243_2&sfvrsn =c5585243_2

^e www.cdc.gov/steadi/pdf/STEADI-Assessment-30Sec-508.pdf

^f www.mdapp.co/mctsib-modified-clinical-test-of-sensory-interaction-in-balance-calculator-404/

^g www.sralab.org/sites/default/files/2017-07/MiniBEST_revised_final_3_8_13.pdf

^h www.neuropt.org/docs/default-source/cpgs/core-outcome-measures/function-gait-assessment-pocket-guide-proof9-(2).pdf?sfvrsn=b4f35043_0

ⁱ www.ncbi.nlm.nih.gov/books/NBK574518/

Natural clay from the earth and its minerals, imperative for survival of life on our planet, have been used for medicinal purposes for thousands of years. An increased interest in clay¹ in dermatopharmacologic and cosmetic or cosmeceutical products has ensued because of its abundance, and for some, the environmental and sustainability viewpoint that minerals will not harm the environment after disposal.

Clay minerals namely consist of silica, alumina, and/or magnesia, and sometimes varying degrees of iron, sodium, potassium, calcium, and water. Depending on the type of clay, as many as 75 trace minerals may be present.
 

Ochre

The first uses of ochre, or natural clay earth pigment, are thought to be by Homo erectus and Homo neanderthalensis who used ochre with water to soothe irritations, heal wounds, and clean skin. The theory is that they mimicked some animals who instinctively used clay/mud/minerals in this manner.

Jami Tarris/Stone/Getty Images

The first recorded use of medicinal clay is on Mesopotamian clay tablets, dating to about 2500 B.C. The ancient Egyptian physicians used clays as anti-inflammatory agents and antiseptics. Clay was also used as a preservative during mummification.

Throughout history, clay has been used for dermatologic purposes. Aristotle (384-322 BC) made one of the first references to deliberately eating clay, earth, or soil by humans for therapeutic and religious purposes. Later, Marco Polo described in his travels seeing Muslim pilgrims cure fevers by ingesting “pink earth.”

The ochres have also long been found in indigenous and aboriginal art, and in current day Namibia, the Himba tribe have used Otjize paste (bright red clay consisting of butterfat, red ochre, and sometimes herbs) for their characteristic hairstyles and makeup, as well as for skin protection and as a soap replacement. Otjize is sacred to the culture and ethnic identity, signifying the beauty of their hair and skin and a sense of oneness with their surroundings (the earth). There are also many instances of religious, folklore, or mythological references of creation of life or creation of humankind from clay.
 

Dermatologic uses

The most common uses of clay in dermatology are for treatment of acne and in spa or cosmeceutical preparations to purportedly draw out dirt, impurities, or toxins.

Clay minerals are most commonly formed from prolonged chemical weathering of silicate-bearing rocks. Clay can also be formed from hydrothermal or volcanic activity. Chemical weathering takes place mainly by acid hydrolysis resulting from low concentrations of carbonic acid, dissolved in rainwater or released by plant roots. Clays differ in composition and structure depending upon the source. Simplistically, clay is structured in two layers, organized in various shapes, with varying minerals and electrical charges. The electric charge of clay allows the adsorption of various minerals, water, heavy and radioactive metals, free radicals, and other potentially unwanted byproducts of metabolic activity. With antibacterial properties and adsorptive properties, clay is often used to dry out acne or oily skin and/or to improve the appearance of large pores.
 

Bentonite clay

Bentonite clay is one of the most common forms of clay used in topical skin products. Bentonite clay, formed after volcanic ash has weathered and aged in the presence of water, is named after a formation called Benton Shale in the western United States. Bentonite has a strong negative electromagnetic charge and when mixed with water it swells like a sponge and can absorb 40-50 times its weight.

There are several types of Bentonite clay, named from the dominant element found within: Sodium bentonite, calcium bentonite, aluminum bentonite, and potassium bentonite are the most common. Bentonite clay is most commonly found in off-white or green colors.

Kaolin and red clay

Typically white or nearly white to sometimes gray in color, kaolin clay is one of the other most common types of clay used in skin care. While the minerals of the kaolin group display a relatively small specific surface area, compared with those of other clay groups, they can still adsorb small molecules, proteins, bacteria, and viruses on the surface of their particles.

Red clay, also sometimes seen in skin care, takes on its color because of a higher content of iron oxides.

In a 2011 study, Valenti et al. evaluated the impact of daily application of clay and retinoic acid 0.025% on the skin of rats.After 7 days, skin where clay had been applied showed a significant increase in collagen fibers, compared with control skin, while areas where retinoic acid had been applied did not show a significant increase in collagen fibers, compared with control skin.²

A recently published study claims that pH and its interaction with the clay particle surface charge may neutralize and impact properties – including antibacterial properties – of clay and is more significant than previously thought.³ The authors emphasize the dangers of this possibility with unregulated marketing and unsubstantiated bioceutical claims of products that contain clay. Many clay-based skin care products on the market today include other ingredients such as acids (for example salicylic acid, lactic acid, and malic acid) that may potentially counteract this issue and help enhance the targeted efficacy of the product.

The types and characteristics of all types of clay go beyond the scope of this column, but as demonstrated throughout history, clay may have a role in medicinal and dermatologic care, the research of which is still ongoing and is important in our understanding of how this earthly compound can affect our bodies.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

References

1: Moraes JDD et al. Int J Pharm. 2017 Dec 20;534(1-2):213-219. doi: 10.1016/j.ijpharm.2017.10.031.

2: Valenti DMZ et al. Clin Exp Dermatol. 2012 Mar;37(2):164-8. doi: 10.1111/j.1365-2230.2011.04216.x

3. Incledion A et al. Biomolecules. 2021 Jan 5;11(1):58. doi: 10.3390/biom11010058.

Natural clay from the earth and its minerals, imperative for survival of life on our planet, have been used for medicinal purposes for thousands of years. An increased interest in clay¹ in dermatopharmacologic and cosmetic or cosmeceutical products has ensued because of its abundance, and for some, the environmental and sustainability viewpoint that minerals will not harm the environment after disposal.

Clay minerals namely consist of silica, alumina, and/or magnesia, and sometimes varying degrees of iron, sodium, potassium, calcium, and water. Depending on the type of clay, as many as 75 trace minerals may be present.
 

Ochre

The first uses of ochre, or natural clay earth pigment, are thought to be by Homo erectus and Homo neanderthalensis who used ochre with water to soothe irritations, heal wounds, and clean skin. The theory is that they mimicked some animals who instinctively used clay/mud/minerals in this manner.

Jami Tarris/Stone/Getty Images

The first recorded use of medicinal clay is on Mesopotamian clay tablets, dating to about 2500 B.C. The ancient Egyptian physicians used clays as anti-inflammatory agents and antiseptics. Clay was also used as a preservative during mummification.

Throughout history, clay has been used for dermatologic purposes. Aristotle (384-322 BC) made one of the first references to deliberately eating clay, earth, or soil by humans for therapeutic and religious purposes. Later, Marco Polo described in his travels seeing Muslim pilgrims cure fevers by ingesting “pink earth.”

The ochres have also long been found in indigenous and aboriginal art, and in current day Namibia, the Himba tribe have used Otjize paste (bright red clay consisting of butterfat, red ochre, and sometimes herbs) for their characteristic hairstyles and makeup, as well as for skin protection and as a soap replacement. Otjize is sacred to the culture and ethnic identity, signifying the beauty of their hair and skin and a sense of oneness with their surroundings (the earth). There are also many instances of religious, folklore, or mythological references of creation of life or creation of humankind from clay.
 

Dermatologic uses

The most common uses of clay in dermatology are for treatment of acne and in spa or cosmeceutical preparations to purportedly draw out dirt, impurities, or toxins.

Clay minerals are most commonly formed from prolonged chemical weathering of silicate-bearing rocks. Clay can also be formed from hydrothermal or volcanic activity. Chemical weathering takes place mainly by acid hydrolysis resulting from low concentrations of carbonic acid, dissolved in rainwater or released by plant roots. Clays differ in composition and structure depending upon the source. Simplistically, clay is structured in two layers, organized in various shapes, with varying minerals and electrical charges. The electric charge of clay allows the adsorption of various minerals, water, heavy and radioactive metals, free radicals, and other potentially unwanted byproducts of metabolic activity. With antibacterial properties and adsorptive properties, clay is often used to dry out acne or oily skin and/or to improve the appearance of large pores.
 

Bentonite clay

Bentonite clay is one of the most common forms of clay used in topical skin products. Bentonite clay, formed after volcanic ash has weathered and aged in the presence of water, is named after a formation called Benton Shale in the western United States. Bentonite has a strong negative electromagnetic charge and when mixed with water it swells like a sponge and can absorb 40-50 times its weight.

There are several types of Bentonite clay, named from the dominant element found within: Sodium bentonite, calcium bentonite, aluminum bentonite, and potassium bentonite are the most common. Bentonite clay is most commonly found in off-white or green colors.

Kaolin and red clay

Typically white or nearly white to sometimes gray in color, kaolin clay is one of the other most common types of clay used in skin care. While the minerals of the kaolin group display a relatively small specific surface area, compared with those of other clay groups, they can still adsorb small molecules, proteins, bacteria, and viruses on the surface of their particles.

Red clay, also sometimes seen in skin care, takes on its color because of a higher content of iron oxides.

In a 2011 study, Valenti et al. evaluated the impact of daily application of clay and retinoic acid 0.025% on the skin of rats.After 7 days, skin where clay had been applied showed a significant increase in collagen fibers, compared with control skin, while areas where retinoic acid had been applied did not show a significant increase in collagen fibers, compared with control skin.²

A recently published study claims that pH and its interaction with the clay particle surface charge may neutralize and impact properties – including antibacterial properties – of clay and is more significant than previously thought.³ The authors emphasize the dangers of this possibility with unregulated marketing and unsubstantiated bioceutical claims of products that contain clay. Many clay-based skin care products on the market today include other ingredients such as acids (for example salicylic acid, lactic acid, and malic acid) that may potentially counteract this issue and help enhance the targeted efficacy of the product.

The types and characteristics of all types of clay go beyond the scope of this column, but as demonstrated throughout history, clay may have a role in medicinal and dermatologic care, the research of which is still ongoing and is important in our understanding of how this earthly compound can affect our bodies.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

References

1: Moraes JDD et al. Int J Pharm. 2017 Dec 20;534(1-2):213-219. doi: 10.1016/j.ijpharm.2017.10.031.

2: Valenti DMZ et al. Clin Exp Dermatol. 2012 Mar;37(2):164-8. doi: 10.1111/j.1365-2230.2011.04216.x

3. Incledion A et al. Biomolecules. 2021 Jan 5;11(1):58. doi: 10.3390/biom11010058.

Natural clay from the earth and its minerals, imperative for survival of life on our planet, have been used for medicinal purposes for thousands of years. An increased interest in clay¹ in dermatopharmacologic and cosmetic or cosmeceutical products has ensued because of its abundance, and for some, the environmental and sustainability viewpoint that minerals will not harm the environment after disposal.

Clay minerals namely consist of silica, alumina, and/or magnesia, and sometimes varying degrees of iron, sodium, potassium, calcium, and water. Depending on the type of clay, as many as 75 trace minerals may be present.
 

Ochre

The first uses of ochre, or natural clay earth pigment, are thought to be by Homo erectus and Homo neanderthalensis who used ochre with water to soothe irritations, heal wounds, and clean skin. The theory is that they mimicked some animals who instinctively used clay/mud/minerals in this manner.

Jami Tarris/Stone/Getty Images

The first recorded use of medicinal clay is on Mesopotamian clay tablets, dating to about 2500 B.C. The ancient Egyptian physicians used clays as anti-inflammatory agents and antiseptics. Clay was also used as a preservative during mummification.

Throughout history, clay has been used for dermatologic purposes. Aristotle (384-322 BC) made one of the first references to deliberately eating clay, earth, or soil by humans for therapeutic and religious purposes. Later, Marco Polo described in his travels seeing Muslim pilgrims cure fevers by ingesting “pink earth.”

The ochres have also long been found in indigenous and aboriginal art, and in current day Namibia, the Himba tribe have used Otjize paste (bright red clay consisting of butterfat, red ochre, and sometimes herbs) for their characteristic hairstyles and makeup, as well as for skin protection and as a soap replacement. Otjize is sacred to the culture and ethnic identity, signifying the beauty of their hair and skin and a sense of oneness with their surroundings (the earth). There are also many instances of religious, folklore, or mythological references of creation of life or creation of humankind from clay.
 

Dermatologic uses

The most common uses of clay in dermatology are for treatment of acne and in spa or cosmeceutical preparations to purportedly draw out dirt, impurities, or toxins.

Clay minerals are most commonly formed from prolonged chemical weathering of silicate-bearing rocks. Clay can also be formed from hydrothermal or volcanic activity. Chemical weathering takes place mainly by acid hydrolysis resulting from low concentrations of carbonic acid, dissolved in rainwater or released by plant roots. Clays differ in composition and structure depending upon the source. Simplistically, clay is structured in two layers, organized in various shapes, with varying minerals and electrical charges. The electric charge of clay allows the adsorption of various minerals, water, heavy and radioactive metals, free radicals, and other potentially unwanted byproducts of metabolic activity. With antibacterial properties and adsorptive properties, clay is often used to dry out acne or oily skin and/or to improve the appearance of large pores.
 

Bentonite clay

Bentonite clay is one of the most common forms of clay used in topical skin products. Bentonite clay, formed after volcanic ash has weathered and aged in the presence of water, is named after a formation called Benton Shale in the western United States. Bentonite has a strong negative electromagnetic charge and when mixed with water it swells like a sponge and can absorb 40-50 times its weight.

There are several types of Bentonite clay, named from the dominant element found within: Sodium bentonite, calcium bentonite, aluminum bentonite, and potassium bentonite are the most common. Bentonite clay is most commonly found in off-white or green colors.

Kaolin and red clay

Typically white or nearly white to sometimes gray in color, kaolin clay is one of the other most common types of clay used in skin care. While the minerals of the kaolin group display a relatively small specific surface area, compared with those of other clay groups, they can still adsorb small molecules, proteins, bacteria, and viruses on the surface of their particles.

Red clay, also sometimes seen in skin care, takes on its color because of a higher content of iron oxides.

In a 2011 study, Valenti et al. evaluated the impact of daily application of clay and retinoic acid 0.025% on the skin of rats.After 7 days, skin where clay had been applied showed a significant increase in collagen fibers, compared with control skin, while areas where retinoic acid had been applied did not show a significant increase in collagen fibers, compared with control skin.²

A recently published study claims that pH and its interaction with the clay particle surface charge may neutralize and impact properties – including antibacterial properties – of clay and is more significant than previously thought.³ The authors emphasize the dangers of this possibility with unregulated marketing and unsubstantiated bioceutical claims of products that contain clay. Many clay-based skin care products on the market today include other ingredients such as acids (for example salicylic acid, lactic acid, and malic acid) that may potentially counteract this issue and help enhance the targeted efficacy of the product.

The types and characteristics of all types of clay go beyond the scope of this column, but as demonstrated throughout history, clay may have a role in medicinal and dermatologic care, the research of which is still ongoing and is important in our understanding of how this earthly compound can affect our bodies.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

References

1: Moraes JDD et al. Int J Pharm. 2017 Dec 20;534(1-2):213-219. doi: 10.1016/j.ijpharm.2017.10.031.

2: Valenti DMZ et al. Clin Exp Dermatol. 2012 Mar;37(2):164-8. doi: 10.1111/j.1365-2230.2011.04216.x

3. Incledion A et al. Biomolecules. 2021 Jan 5;11(1):58. doi: 10.3390/biom11010058.

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Americans keep hearing that it is important to test frequently for COVID-19 at home. But just try to find an “at-home” rapid COVID test in a store and at a price that makes frequent tests affordable.

Testing, as well as mask-wearing, is an important measure if the country ever hopes to beat COVID, restore normal routines and get the economy running efficiently. To get Americans cheaper tests, the federal government now plans to have insurance companies pay for them.

The Biden administration announced Jan. 10 that every person with private insurance can get full coverage for eight rapid tests a month. You can either get one without any out-of-pocket expense from retail pharmacies that are part of an insurance company’s network or buy it at any store and get reimbursed by the insurer.

Congress said private insurers must cover all COVID testing and any associated medical services when it passed the Families First Coronavirus Response Act and the Coronavirus Aid, Relief and Economic Security, or CARES, Act. The have-insurance-pay-for-it solution has been used frequently through the pandemic. Insurance companies have been told to pay for polymerase chain reaction tests, COVID treatments and the administration of vaccines. (Taxpayers are paying for the cost of the vaccines themselves.) It appears to be an elegant solution for a politician because it looks free and isn’t using taxpayer money.

1. Are the tests really free?

Well, no. As many an economist will tell you, there ain’t no such thing as a free lunch. Someone has to pick up the tab. Initially, the insurance companies bear the cost. Cynthia Cox, a vice president at KFF who studies the Affordable Care Act and private insurers, said the total bill could amount to billions of dollars. Exactly how much depends on “how easy it is to get them, and how many will be reimbursed,” she said.

2. Will the insurance company just swallow those imposed costs?

If companies draw from the time-tested insurance giants’ playbook, they’ll pass along those costs to customers. “This will put upward pressure on premiums,” said Emily Gee, vice president and coordinator for health policy at the Center for American Progress.

Major insurance companies like Cigna, Anthem, UnitedHealthcare, and Aetna did not respond to requests to discuss this issue.

3. If that’s the case, why haven’t I been hit with higher premiums already?

Insurance companies had the chance last year to raise premiums but, mostly, they did not.

Why? Perhaps because insurers have so far made so much money during the pandemic they didn’t need to. For example, the industry’s profits in 2020 increased 41% to $31 billion from $22 billion, according to the National Association of Insurance Commissioners. The NAIC said the industry has continued its “tremendous growth trend” that started before COVID emerged. Companies will be reporting 2021 results soon.

The reason behind these profits is clear. You were paying premiums based on projections your insurance company made about how much health care consumers would use that year. Because people stayed home, had fewer accidents, postponed surgeries and often avoided going to visit the doctor or the hospital, insurers paid out less. They rebated some of their earnings back to customers, but they pocketed a lot more.

As the companies’ actuaries work on predicting 2023 expenditures, premiums could go up if they foresee more claims and expenses. Paying for millions of rapid tests is something they would include in their calculations.

4. Regardless of my premiums, will the tests cost me money directly?

It’s quite possible. If your insurance company doesn’t have an arrangement with a retailer where you can simply pick up your allotted tests, you’ll have to pay for them – at whatever price the store sets. If that’s the case, you’ll need to fill out a form to request a reimbursement from the insurance company. How many times have you lost receipts or just plain neglected to mail in for rebates on something you bought? A lot, right?

Here’s another thing: The reimbursement is set at $12 per test. If you pay $30 for a test – and that is not unheard of – your insurer is only on the hook for $12. You eat the $18.

And by the way, people on Medicare will have to pay for their tests themselves. People who get their health care covered by Medicaid can obtain free test kits at community centers.

A few free tests are supposed to arrive at every American home via the U.S. Postal Service. And the Biden administration has activated a website where Americans can order free tests from a cache of a billion the federal government ordered.

5. Will this help bring down the costs of at-home tests and make them easier to find?

The free COVID tests are unlikely to have much immediate impact on general cost and availability. You will still need to search for them. The federal measures likely will stimulate the demand for tests, which in the short term may make them harder to find.

But the demand, and some government guarantees to manufacturers, may induce test makers to make more of them faster. The increased competition and supply theoretically could bring down the price. There is certainly room for prices to decline since the wholesale cost of the test is between $5 and $7, analysts estimate. “It’s a big step in the right direction,” Ms. Gee said.
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Americans keep hearing that it is important to test frequently for COVID-19 at home. But just try to find an “at-home” rapid COVID test in a store and at a price that makes frequent tests affordable.

Testing, as well as mask-wearing, is an important measure if the country ever hopes to beat COVID, restore normal routines and get the economy running efficiently. To get Americans cheaper tests, the federal government now plans to have insurance companies pay for them.

The Biden administration announced Jan. 10 that every person with private insurance can get full coverage for eight rapid tests a month. You can either get one without any out-of-pocket expense from retail pharmacies that are part of an insurance company’s network or buy it at any store and get reimbursed by the insurer.

Congress said private insurers must cover all COVID testing and any associated medical services when it passed the Families First Coronavirus Response Act and the Coronavirus Aid, Relief and Economic Security, or CARES, Act. The have-insurance-pay-for-it solution has been used frequently through the pandemic. Insurance companies have been told to pay for polymerase chain reaction tests, COVID treatments and the administration of vaccines. (Taxpayers are paying for the cost of the vaccines themselves.) It appears to be an elegant solution for a politician because it looks free and isn’t using taxpayer money.

1. Are the tests really free?

Well, no. As many an economist will tell you, there ain’t no such thing as a free lunch. Someone has to pick up the tab. Initially, the insurance companies bear the cost. Cynthia Cox, a vice president at KFF who studies the Affordable Care Act and private insurers, said the total bill could amount to billions of dollars. Exactly how much depends on “how easy it is to get them, and how many will be reimbursed,” she said.

2. Will the insurance company just swallow those imposed costs?

If companies draw from the time-tested insurance giants’ playbook, they’ll pass along those costs to customers. “This will put upward pressure on premiums,” said Emily Gee, vice president and coordinator for health policy at the Center for American Progress.

Major insurance companies like Cigna, Anthem, UnitedHealthcare, and Aetna did not respond to requests to discuss this issue.

3. If that’s the case, why haven’t I been hit with higher premiums already?

Insurance companies had the chance last year to raise premiums but, mostly, they did not.

Why? Perhaps because insurers have so far made so much money during the pandemic they didn’t need to. For example, the industry’s profits in 2020 increased 41% to $31 billion from $22 billion, according to the National Association of Insurance Commissioners. The NAIC said the industry has continued its “tremendous growth trend” that started before COVID emerged. Companies will be reporting 2021 results soon.

The reason behind these profits is clear. You were paying premiums based on projections your insurance company made about how much health care consumers would use that year. Because people stayed home, had fewer accidents, postponed surgeries and often avoided going to visit the doctor or the hospital, insurers paid out less. They rebated some of their earnings back to customers, but they pocketed a lot more.

As the companies’ actuaries work on predicting 2023 expenditures, premiums could go up if they foresee more claims and expenses. Paying for millions of rapid tests is something they would include in their calculations.

4. Regardless of my premiums, will the tests cost me money directly?

It’s quite possible. If your insurance company doesn’t have an arrangement with a retailer where you can simply pick up your allotted tests, you’ll have to pay for them – at whatever price the store sets. If that’s the case, you’ll need to fill out a form to request a reimbursement from the insurance company. How many times have you lost receipts or just plain neglected to mail in for rebates on something you bought? A lot, right?

Here’s another thing: The reimbursement is set at $12 per test. If you pay $30 for a test – and that is not unheard of – your insurer is only on the hook for $12. You eat the $18.

And by the way, people on Medicare will have to pay for their tests themselves. People who get their health care covered by Medicaid can obtain free test kits at community centers.

A few free tests are supposed to arrive at every American home via the U.S. Postal Service. And the Biden administration has activated a website where Americans can order free tests from a cache of a billion the federal government ordered.

5. Will this help bring down the costs of at-home tests and make them easier to find?

The free COVID tests are unlikely to have much immediate impact on general cost and availability. You will still need to search for them. The federal measures likely will stimulate the demand for tests, which in the short term may make them harder to find.

But the demand, and some government guarantees to manufacturers, may induce test makers to make more of them faster. The increased competition and supply theoretically could bring down the price. There is certainly room for prices to decline since the wholesale cost of the test is between $5 and $7, analysts estimate. “It’s a big step in the right direction,” Ms. Gee said.
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Americans keep hearing that it is important to test frequently for COVID-19 at home. But just try to find an “at-home” rapid COVID test in a store and at a price that makes frequent tests affordable.

Testing, as well as mask-wearing, is an important measure if the country ever hopes to beat COVID, restore normal routines and get the economy running efficiently. To get Americans cheaper tests, the federal government now plans to have insurance companies pay for them.

The Biden administration announced Jan. 10 that every person with private insurance can get full coverage for eight rapid tests a month. You can either get one without any out-of-pocket expense from retail pharmacies that are part of an insurance company’s network or buy it at any store and get reimbursed by the insurer.

Congress said private insurers must cover all COVID testing and any associated medical services when it passed the Families First Coronavirus Response Act and the Coronavirus Aid, Relief and Economic Security, or CARES, Act. The have-insurance-pay-for-it solution has been used frequently through the pandemic. Insurance companies have been told to pay for polymerase chain reaction tests, COVID treatments and the administration of vaccines. (Taxpayers are paying for the cost of the vaccines themselves.) It appears to be an elegant solution for a politician because it looks free and isn’t using taxpayer money.

1. Are the tests really free?

Well, no. As many an economist will tell you, there ain’t no such thing as a free lunch. Someone has to pick up the tab. Initially, the insurance companies bear the cost. Cynthia Cox, a vice president at KFF who studies the Affordable Care Act and private insurers, said the total bill could amount to billions of dollars. Exactly how much depends on “how easy it is to get them, and how many will be reimbursed,” she said.

2. Will the insurance company just swallow those imposed costs?

If companies draw from the time-tested insurance giants’ playbook, they’ll pass along those costs to customers. “This will put upward pressure on premiums,” said Emily Gee, vice president and coordinator for health policy at the Center for American Progress.

Major insurance companies like Cigna, Anthem, UnitedHealthcare, and Aetna did not respond to requests to discuss this issue.

3. If that’s the case, why haven’t I been hit with higher premiums already?

Insurance companies had the chance last year to raise premiums but, mostly, they did not.

Why? Perhaps because insurers have so far made so much money during the pandemic they didn’t need to. For example, the industry’s profits in 2020 increased 41% to $31 billion from $22 billion, according to the National Association of Insurance Commissioners. The NAIC said the industry has continued its “tremendous growth trend” that started before COVID emerged. Companies will be reporting 2021 results soon.

The reason behind these profits is clear. You were paying premiums based on projections your insurance company made about how much health care consumers would use that year. Because people stayed home, had fewer accidents, postponed surgeries and often avoided going to visit the doctor or the hospital, insurers paid out less. They rebated some of their earnings back to customers, but they pocketed a lot more.

As the companies’ actuaries work on predicting 2023 expenditures, premiums could go up if they foresee more claims and expenses. Paying for millions of rapid tests is something they would include in their calculations.

4. Regardless of my premiums, will the tests cost me money directly?

It’s quite possible. If your insurance company doesn’t have an arrangement with a retailer where you can simply pick up your allotted tests, you’ll have to pay for them – at whatever price the store sets. If that’s the case, you’ll need to fill out a form to request a reimbursement from the insurance company. How many times have you lost receipts or just plain neglected to mail in for rebates on something you bought? A lot, right?

Here’s another thing: The reimbursement is set at $12 per test. If you pay $30 for a test – and that is not unheard of – your insurer is only on the hook for $12. You eat the $18.

And by the way, people on Medicare will have to pay for their tests themselves. People who get their health care covered by Medicaid can obtain free test kits at community centers.

A few free tests are supposed to arrive at every American home via the U.S. Postal Service. And the Biden administration has activated a website where Americans can order free tests from a cache of a billion the federal government ordered.

5. Will this help bring down the costs of at-home tests and make them easier to find?

The free COVID tests are unlikely to have much immediate impact on general cost and availability. You will still need to search for them. The federal measures likely will stimulate the demand for tests, which in the short term may make them harder to find.

But the demand, and some government guarantees to manufacturers, may induce test makers to make more of them faster. The increased competition and supply theoretically could bring down the price. There is certainly room for prices to decline since the wholesale cost of the test is between $5 and $7, analysts estimate. “It’s a big step in the right direction,” Ms. Gee said.
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

A version of this article first appeared on Medscape.com.

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

A version of this article first appeared on Medscape.com.

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

A version of this article first appeared on Medscape.com.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

A version of this article first appeared on Medscape.com.

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

A version of this article first appeared on Medscape.com.

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

A version of this article first appeared on Medscape.com.

Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.