Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Lesinurad (Zurampic) has been approved to treat hyperuricemia associated with gout, when used in combination with a xanthine oxidase inhibitor, the Food and Drug Administration announced on Dec. 22.

Lesinurad promotes uric acid excretion by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

“Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes,” said Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The drug’s safety and efficacy were evaluated in 1,537 participants in three randomized, placebo-controlled studies of its use in combination with a xanthine oxidase inhibitor. Participants treated for up to 12 months with lesinurad experienced reduced serum uric acid levels, compared with participants given placebo.

The most common adverse reactions in the clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease. Lesinurad has a boxed warning that provides important safety information, including the risk for acute renal failure, which is more common when lesinurad is used without a xanthine oxidase inhibitor and with higher-than-approved doses.

The FDA also said in its statement that the agency is requiring a postmarketing study to further evaluate the renal and cardiovascular safety of lesinurad.

Zurampic is manufactured by AstraZeneca Pharmaceuticals.

[email protected]

On Twitter @maryjodales

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Never before in history has medicine progressed as quickly as it does today. The half-life of knowledge and practices is shortening, and the ocean of literature continues to amass every day. In this context, it is simply not possible for training programs to teach in didactics everything residents must know to become competent, much less excellent, doctors. Self-directed learning has become a critical part of residents’ education.

How can we make self-directed learning a more successful process? Attending physicians are likely to answer with the old saying, ‘You can lead a horse to water, but you can’t make it drink!’ While this saying points to the fact that self-directed learning requires a thirsty horse, it takes for granted the role of the guide in showing where water is plentiful. We argue that residents’ self-directed learning can be made more successful by recognizing the role of attendings in this process.

In an era of infinite resources, the limiting factor to learning has become time. The more we learn, the more humbled we are by the vastness of what we don’t know. Self-directed learners must be smart in deciding what should be learned. Herein lies the value of attendings, who, whether we are aware or not, shape our learning simply by virtue of their example. We would do well to pay closer attention to them. No textbook can replace their vast experience, which allows them to hone in on relevant details, to quickly develop comprehensive differentials, or revise plans.

But this learning cannot be based on simply observing and blindly emulating our teachers. We refer to Dr. Bloom’s taxonomy for levels of cognitive learning, in saying that these steps will only get us to the most basic levels of learning, which is “knowing” a disease to the extent that we can apply that knowledge in patient care. These can be acquired without significant mental effort; just by listening to morning reports, reading quick tidbits in between taking care of patients, etc. The goal, however, should be utilizing this basic knowledge as a foundation to develop higher levels of learning, namely Analysis, Synthesis, and Evaluation.

An example for analysis would be quickly going over each of the differentials in a disease and learning what distinguishes them. Synthesis is integrating different ideas and creating a customized plan for the particular patient that is found in no book. Lastly, evaluation is the level of cognition needed to be able to appraise and critique the large volume of opinion that we come across, establish our own opinion, and be able to defend it.

Here again our attendings are valuable resources who can guide us in reaching each of these levels. We must be willing to challenge ourselves by challenging our attendings when things do not make sense. It means always questioning why your attending physician made one medical decision versus another. It means also to challenge what we think we know, in order to discover what we don’t know. … Returning to the old adage, perhaps the key to self-directed learning is for the horse to learn his masters’ ways to the well, so he may adapt to an ever-changing environment.

Dr. Hung and Dr. Ramakrishna are pediatric residents at the Metrohealth Medical Center in Cleveland, Ohio. Email them at [email protected].

Never before in history has medicine progressed as quickly as it does today. The half-life of knowledge and practices is shortening, and the ocean of literature continues to amass every day. In this context, it is simply not possible for training programs to teach in didactics everything residents must know to become competent, much less excellent, doctors. Self-directed learning has become a critical part of residents’ education.

How can we make self-directed learning a more successful process? Attending physicians are likely to answer with the old saying, ‘You can lead a horse to water, but you can’t make it drink!’ While this saying points to the fact that self-directed learning requires a thirsty horse, it takes for granted the role of the guide in showing where water is plentiful. We argue that residents’ self-directed learning can be made more successful by recognizing the role of attendings in this process.

In an era of infinite resources, the limiting factor to learning has become time. The more we learn, the more humbled we are by the vastness of what we don’t know. Self-directed learners must be smart in deciding what should be learned. Herein lies the value of attendings, who, whether we are aware or not, shape our learning simply by virtue of their example. We would do well to pay closer attention to them. No textbook can replace their vast experience, which allows them to hone in on relevant details, to quickly develop comprehensive differentials, or revise plans.

But this learning cannot be based on simply observing and blindly emulating our teachers. We refer to Dr. Bloom’s taxonomy for levels of cognitive learning, in saying that these steps will only get us to the most basic levels of learning, which is “knowing” a disease to the extent that we can apply that knowledge in patient care. These can be acquired without significant mental effort; just by listening to morning reports, reading quick tidbits in between taking care of patients, etc. The goal, however, should be utilizing this basic knowledge as a foundation to develop higher levels of learning, namely Analysis, Synthesis, and Evaluation.

An example for analysis would be quickly going over each of the differentials in a disease and learning what distinguishes them. Synthesis is integrating different ideas and creating a customized plan for the particular patient that is found in no book. Lastly, evaluation is the level of cognition needed to be able to appraise and critique the large volume of opinion that we come across, establish our own opinion, and be able to defend it.

Here again our attendings are valuable resources who can guide us in reaching each of these levels. We must be willing to challenge ourselves by challenging our attendings when things do not make sense. It means always questioning why your attending physician made one medical decision versus another. It means also to challenge what we think we know, in order to discover what we don’t know. … Returning to the old adage, perhaps the key to self-directed learning is for the horse to learn his masters’ ways to the well, so he may adapt to an ever-changing environment.

Dr. Hung and Dr. Ramakrishna are pediatric residents at the Metrohealth Medical Center in Cleveland, Ohio. Email them at [email protected].

Never before in history has medicine progressed as quickly as it does today. The half-life of knowledge and practices is shortening, and the ocean of literature continues to amass every day. In this context, it is simply not possible for training programs to teach in didactics everything residents must know to become competent, much less excellent, doctors. Self-directed learning has become a critical part of residents’ education.

How can we make self-directed learning a more successful process? Attending physicians are likely to answer with the old saying, ‘You can lead a horse to water, but you can’t make it drink!’ While this saying points to the fact that self-directed learning requires a thirsty horse, it takes for granted the role of the guide in showing where water is plentiful. We argue that residents’ self-directed learning can be made more successful by recognizing the role of attendings in this process.

In an era of infinite resources, the limiting factor to learning has become time. The more we learn, the more humbled we are by the vastness of what we don’t know. Self-directed learners must be smart in deciding what should be learned. Herein lies the value of attendings, who, whether we are aware or not, shape our learning simply by virtue of their example. We would do well to pay closer attention to them. No textbook can replace their vast experience, which allows them to hone in on relevant details, to quickly develop comprehensive differentials, or revise plans.

But this learning cannot be based on simply observing and blindly emulating our teachers. We refer to Dr. Bloom’s taxonomy for levels of cognitive learning, in saying that these steps will only get us to the most basic levels of learning, which is “knowing” a disease to the extent that we can apply that knowledge in patient care. These can be acquired without significant mental effort; just by listening to morning reports, reading quick tidbits in between taking care of patients, etc. The goal, however, should be utilizing this basic knowledge as a foundation to develop higher levels of learning, namely Analysis, Synthesis, and Evaluation.

An example for analysis would be quickly going over each of the differentials in a disease and learning what distinguishes them. Synthesis is integrating different ideas and creating a customized plan for the particular patient that is found in no book. Lastly, evaluation is the level of cognition needed to be able to appraise and critique the large volume of opinion that we come across, establish our own opinion, and be able to defend it.

Here again our attendings are valuable resources who can guide us in reaching each of these levels. We must be willing to challenge ourselves by challenging our attendings when things do not make sense. It means always questioning why your attending physician made one medical decision versus another. It means also to challenge what we think we know, in order to discover what we don’t know. … Returning to the old adage, perhaps the key to self-directed learning is for the horse to learn his masters’ ways to the well, so he may adapt to an ever-changing environment.

Dr. Hung and Dr. Ramakrishna are pediatric residents at the Metrohealth Medical Center in Cleveland, Ohio. Email them at [email protected].

Since 2005, I’ve had the opportunity to review “Pearls” articles submitted for publication in Current Psychiatry. In that time, I have read many worthwhile papers written by authors who may not be entirely clear about what constitutes a “Pearl." The mnemonic PEARL could help authors:

• decide if their article or idea is appropriate for “Pearls”
• construct the article to conform to the “Pearls” format.

Easy to remember. Lengthy, highly detailed articles may be helpful and informative but are not consistent with the purpose of “Pearls.

Alert. A “Pearl” should alert a physician to identify a problem, diagnosis, or adverse effect that they might otherwise miss or take unnecessary time to identify. Classic examples are the “handshake diagnosis” of hyperthyroidism,¹ or the “3 little words that can diagnose mild cognitive impairment.”²

References. A professional article of any length should include references. References add immediate credibility to the information presented. For a “Pearl,” even 1 reference is acceptable. A writer can easily search PubMed and the Internet to find references to confirm or support their ideas.
 

Less is more. Architect Mies van der Rohe’s minimalist concept applies to “Pearls.” A “Pearl”—like its namesake—is small, polished, and valuable. Simplicity is its essence.

I hope this mnemonic is useful for clinicians interested in sharing their ideas or experiences to help others in the field. I look forward to reviewing many more “Pearls.”

Since 2005, I’ve had the opportunity to review “Pearls” articles submitted for publication in Current Psychiatry. In that time, I have read many worthwhile papers written by authors who may not be entirely clear about what constitutes a “Pearl." The mnemonic PEARL could help authors:

• decide if their article or idea is appropriate for “Pearls”
• construct the article to conform to the “Pearls” format.

Easy to remember. Lengthy, highly detailed articles may be helpful and informative but are not consistent with the purpose of “Pearls.

Alert. A “Pearl” should alert a physician to identify a problem, diagnosis, or adverse effect that they might otherwise miss or take unnecessary time to identify. Classic examples are the “handshake diagnosis” of hyperthyroidism,¹ or the “3 little words that can diagnose mild cognitive impairment.”²

References. A professional article of any length should include references. References add immediate credibility to the information presented. For a “Pearl,” even 1 reference is acceptable. A writer can easily search PubMed and the Internet to find references to confirm or support their ideas.
 

Less is more. Architect Mies van der Rohe’s minimalist concept applies to “Pearls.” A “Pearl”—like its namesake—is small, polished, and valuable. Simplicity is its essence.

I hope this mnemonic is useful for clinicians interested in sharing their ideas or experiences to help others in the field. I look forward to reviewing many more “Pearls.”

Since 2005, I’ve had the opportunity to review “Pearls” articles submitted for publication in Current Psychiatry. In that time, I have read many worthwhile papers written by authors who may not be entirely clear about what constitutes a “Pearl." The mnemonic PEARL could help authors:

• decide if their article or idea is appropriate for “Pearls”
• construct the article to conform to the “Pearls” format.

Easy to remember. Lengthy, highly detailed articles may be helpful and informative but are not consistent with the purpose of “Pearls.

Alert. A “Pearl” should alert a physician to identify a problem, diagnosis, or adverse effect that they might otherwise miss or take unnecessary time to identify. Classic examples are the “handshake diagnosis” of hyperthyroidism,¹ or the “3 little words that can diagnose mild cognitive impairment.”²

References. A professional article of any length should include references. References add immediate credibility to the information presented. For a “Pearl,” even 1 reference is acceptable. A writer can easily search PubMed and the Internet to find references to confirm or support their ideas.
 

Less is more. Architect Mies van der Rohe’s minimalist concept applies to “Pearls.” A “Pearl”—like its namesake—is small, polished, and valuable. Simplicity is its essence.

I hope this mnemonic is useful for clinicians interested in sharing their ideas or experiences to help others in the field. I look forward to reviewing many more “Pearls.”

Two years ago, a mother of one of my patients asked me for advice. She knew that her daughter identified as lesbian, and she was fully supportive. One day, her daughter wanted to go to a sleepover at a female friend’s house. Her first reaction was to say yes, but then she had second thoughts: If her daughter were straight, and this friend were male, she would not allow her to go because of the potential for sexual activity. When she told her daughter she could not attend the sleepover, her daughter accused her of not letting her go because of her sexual orientation. And now, the dilemma: In her effort to be fair and consistent with her values, the mother is being accused of discrimination. What should she do?

Parents play an irreplaceable role in the life of any teen, especially in the lives of teens that identify as lesbian, gay, bisexual, or transgender (LGBT). But many LGBT youth face serious challenges with their parents. They face the potential of parental rejection of their sexual or gender identity. At the very worst, teens may face homelessness if they come out to homophobic parents.¹ Youth whose parents are accepting, nevertheless, are less likely to have mental health problems or engage in substance use.²

As a clinical provider for children and adolescents, caregivers will ask you for advice on how to address parenting challenges. Because LGBT youth are at risk for many adverse health outcomes, and parental support is paramount in preventing them, this is an opportunity for you to help this vulnerable population.

If parents ask you how to be supportive of their LGBT children, here are some recommendations, which are based on an intervention by colleagues at the University of Utah:³

1. Let their affection show. Receiving news that a child is LGBT can be emotionally intense for parents.⁴ Because of this emotional intensity, parents may react negatively and neglect to show their love for their child, which is what the child is seeking. Parents showing affection is the first step in supporting their LGBT child. Remind parents to tell their child that they love them no matter what.

2. Avoid rejecting behaviors. This is sometimes hard, because some forms of rejection can be quite subtle. Avoid saying anything that may indicate a negative view of LGBT people, even if it is not intended. For example, saying that something is “gay” may seem innocent enough, but it sends the message that being gay is something to be ashamed of.

3. Express their pain away from their child. Evidence shows that minimizing a child’s exposure to parental conflict and stress is associated with better coping with these devastating events.⁵ Parents should avoid telling their children that news of their sexual orientation or gender identity upsets them, as this is another form of rejecting behavior.

4. Do good before they feel good. Previous studies suggest that changes in behavior can occur even though a person may feel otherwise.⁶ Negative feelings about a child’s sexual orientation or gender identity can last months or years.⁷ It’s okay to have these feelings, but showing support such as telling their child how they still love them can ultimately lead to acceptance.

Although it is important for parents to accept their child, it is only half the battle. If you remember Baumrind’s theory on parenting, there are two sides of parenting. The first side involves parents showing their affection, love, and support for their children, which I described earlier. The other side involves managing a child’s behaviors, whether parents create an environment that makes it difficult to engage in behaviors they disapprove of or teach their children how to make the right decision.⁸ Many LGBT youth engage in risky behaviors because it’s a way of coping in a homophobic environment. The parents’ job is to teach their children healthier coping strategies.

Research on this aspect of parenting in LGBT youth is still at its infancy, and some of it is not reassuring. One important behavior, parental monitoring, which is “a set of correlated parenting behaviors involving attention to and tracking of the child’s whereabouts, activities, and adaptations,”⁹ can prevent conduct disorders, substance use, and mental health problems in the typical teenager.¹⁰ Unfortunately, we don’t find the same results for sexual minorities. One study suggests that parental monitoring may not prevent high-risk sexual behavior for young gay males, even if the parent is aware of the young man’s sexual orientation.¹¹

This doesn’t mean that parental monitoring isn’t helpful. This just means that parenting LGBT youth is different than parenting heterosexual youth. It’s not enough for parents to just accept their child’s sexual orientation. They also must help them make the right decisions taking into consideration the effect of stigma and discrimination on sexual minorities. There are a couple of things you can suggest to your parents to help them raise their LGBT children:

1. Be proactive. Join organizations that support parents of LGBT youth such as Parents, Families, and Friends of Lesbians and Gays (PFLAG). Also, parents must be aware of their children’s behavior. If they are acting depressed, seek help. Having depression or anxiety increases the chances of engaging in risky behaviors, so the earlier parents address this, the better.

2. Make their child know what their views are on high risk-behaviors, such as substance use or having unprotected sex. They need to communicate their expectations clearly. If parents believe that drinking alcohol before the legal age is wrong, they should clearly let their children know that.

3. Make it easier for their child to tell parents what’s going on in their lives. Parents have to gain their children’s trust, be accessible (don’t answer texts while talking to them!), and be an active listener. LGBT youth may not ask parents for advice because they feel that because their parents are straight or cisgender, their life experiences do not apply. Being a member of an organization like PLFAG can be helpful, because parents can ask other parents who have experience raising LGBT youth for advice that works.

4. If parents’ children do something wrong, they should talk to them about how their actions were risky. Children will listen to parents if they view their parenting as legitimate and fair, which can only happen if there is a strong parent-child relationship. Being supportive of a child’s sexual orientation or gender identity is key here. And for the next time, it’s always good to role-play a scenario (for example, what to do if someone tries to make them drink at a party).

Parents of LGBT youth face many challenges. You can help these parents by encouraging them to accept and support their child’s sexual orientation or gender identity and provide parenting strategies relevant for LGBT youth. Most important of all, encourage them to seek support through organizations like PFLAG. With this support, parents can encourage healthy development in LGBT youth.

Resources for parents of LGBT youth

• The Centers for Disease Control and Prevention (CDC) has information on the health of LGBT Youth and advice on parental monitoring in general.

• The Family Acceptance Project is a project researching ways to improve parent-child relationships in LGBT Youth.

• PFLAG is an organization that provides support for families of LGBT youth.

• Lead with Love is a film about how various types of families react to their children coming out to them.

References

1. J Sex Res. 2004 Nov;41(4):329-42.

2. Aust N Z J Psychiatry. 2010 Sep;44(9):774-83.

3. Huebner D. “Leading with Love: Interventions to Support Families of Lesbian, Gay, and Bisexual Adolescents,” The Register Report, Vol. 39. National Register of Health Service Psychologists, Spring 2013.

4. J GLBT Fam Stud. 2014 Jan;10(1-2):36-57.

5. Prof Psychol Res Pr. 2008 Apr;39(2):113-21.

6. “Behaviorism: Classic Studies” (Casper, Wyo: Endeavor Books/Mountain States Litho, 2009).

7. Journal of LGBT Issues in Counseling. 2008;2(2):126-58.

8. Genet Psychol Monogr. 1967;75(1):43-88.

9. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.

10. “Parental Monitoring of Adolescents: Current Perspectives for Researchers and Practitioners” (New York: Columbia University Press, 2010).

11. AIDS Behav. 2014 Aug;18(8):1604-14.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

Two years ago, a mother of one of my patients asked me for advice. She knew that her daughter identified as lesbian, and she was fully supportive. One day, her daughter wanted to go to a sleepover at a female friend’s house. Her first reaction was to say yes, but then she had second thoughts: If her daughter were straight, and this friend were male, she would not allow her to go because of the potential for sexual activity. When she told her daughter she could not attend the sleepover, her daughter accused her of not letting her go because of her sexual orientation. And now, the dilemma: In her effort to be fair and consistent with her values, the mother is being accused of discrimination. What should she do?

Parents play an irreplaceable role in the life of any teen, especially in the lives of teens that identify as lesbian, gay, bisexual, or transgender (LGBT). But many LGBT youth face serious challenges with their parents. They face the potential of parental rejection of their sexual or gender identity. At the very worst, teens may face homelessness if they come out to homophobic parents.¹ Youth whose parents are accepting, nevertheless, are less likely to have mental health problems or engage in substance use.²

As a clinical provider for children and adolescents, caregivers will ask you for advice on how to address parenting challenges. Because LGBT youth are at risk for many adverse health outcomes, and parental support is paramount in preventing them, this is an opportunity for you to help this vulnerable population.

If parents ask you how to be supportive of their LGBT children, here are some recommendations, which are based on an intervention by colleagues at the University of Utah:³

1. Let their affection show. Receiving news that a child is LGBT can be emotionally intense for parents.⁴ Because of this emotional intensity, parents may react negatively and neglect to show their love for their child, which is what the child is seeking. Parents showing affection is the first step in supporting their LGBT child. Remind parents to tell their child that they love them no matter what.

2. Avoid rejecting behaviors. This is sometimes hard, because some forms of rejection can be quite subtle. Avoid saying anything that may indicate a negative view of LGBT people, even if it is not intended. For example, saying that something is “gay” may seem innocent enough, but it sends the message that being gay is something to be ashamed of.

3. Express their pain away from their child. Evidence shows that minimizing a child’s exposure to parental conflict and stress is associated with better coping with these devastating events.⁵ Parents should avoid telling their children that news of their sexual orientation or gender identity upsets them, as this is another form of rejecting behavior.

4. Do good before they feel good. Previous studies suggest that changes in behavior can occur even though a person may feel otherwise.⁶ Negative feelings about a child’s sexual orientation or gender identity can last months or years.⁷ It’s okay to have these feelings, but showing support such as telling their child how they still love them can ultimately lead to acceptance.

Although it is important for parents to accept their child, it is only half the battle. If you remember Baumrind’s theory on parenting, there are two sides of parenting. The first side involves parents showing their affection, love, and support for their children, which I described earlier. The other side involves managing a child’s behaviors, whether parents create an environment that makes it difficult to engage in behaviors they disapprove of or teach their children how to make the right decision.⁸ Many LGBT youth engage in risky behaviors because it’s a way of coping in a homophobic environment. The parents’ job is to teach their children healthier coping strategies.

Research on this aspect of parenting in LGBT youth is still at its infancy, and some of it is not reassuring. One important behavior, parental monitoring, which is “a set of correlated parenting behaviors involving attention to and tracking of the child’s whereabouts, activities, and adaptations,”⁹ can prevent conduct disorders, substance use, and mental health problems in the typical teenager.¹⁰ Unfortunately, we don’t find the same results for sexual minorities. One study suggests that parental monitoring may not prevent high-risk sexual behavior for young gay males, even if the parent is aware of the young man’s sexual orientation.¹¹

This doesn’t mean that parental monitoring isn’t helpful. This just means that parenting LGBT youth is different than parenting heterosexual youth. It’s not enough for parents to just accept their child’s sexual orientation. They also must help them make the right decisions taking into consideration the effect of stigma and discrimination on sexual minorities. There are a couple of things you can suggest to your parents to help them raise their LGBT children:

1. Be proactive. Join organizations that support parents of LGBT youth such as Parents, Families, and Friends of Lesbians and Gays (PFLAG). Also, parents must be aware of their children’s behavior. If they are acting depressed, seek help. Having depression or anxiety increases the chances of engaging in risky behaviors, so the earlier parents address this, the better.

2. Make their child know what their views are on high risk-behaviors, such as substance use or having unprotected sex. They need to communicate their expectations clearly. If parents believe that drinking alcohol before the legal age is wrong, they should clearly let their children know that.

3. Make it easier for their child to tell parents what’s going on in their lives. Parents have to gain their children’s trust, be accessible (don’t answer texts while talking to them!), and be an active listener. LGBT youth may not ask parents for advice because they feel that because their parents are straight or cisgender, their life experiences do not apply. Being a member of an organization like PLFAG can be helpful, because parents can ask other parents who have experience raising LGBT youth for advice that works.

4. If parents’ children do something wrong, they should talk to them about how their actions were risky. Children will listen to parents if they view their parenting as legitimate and fair, which can only happen if there is a strong parent-child relationship. Being supportive of a child’s sexual orientation or gender identity is key here. And for the next time, it’s always good to role-play a scenario (for example, what to do if someone tries to make them drink at a party).

Parents of LGBT youth face many challenges. You can help these parents by encouraging them to accept and support their child’s sexual orientation or gender identity and provide parenting strategies relevant for LGBT youth. Most important of all, encourage them to seek support through organizations like PFLAG. With this support, parents can encourage healthy development in LGBT youth.

Resources for parents of LGBT youth

• The Centers for Disease Control and Prevention (CDC) has information on the health of LGBT Youth and advice on parental monitoring in general.

• The Family Acceptance Project is a project researching ways to improve parent-child relationships in LGBT Youth.

• PFLAG is an organization that provides support for families of LGBT youth.

• Lead with Love is a film about how various types of families react to their children coming out to them.

References

1. J Sex Res. 2004 Nov;41(4):329-42.

2. Aust N Z J Psychiatry. 2010 Sep;44(9):774-83.

3. Huebner D. “Leading with Love: Interventions to Support Families of Lesbian, Gay, and Bisexual Adolescents,” The Register Report, Vol. 39. National Register of Health Service Psychologists, Spring 2013.

4. J GLBT Fam Stud. 2014 Jan;10(1-2):36-57.

5. Prof Psychol Res Pr. 2008 Apr;39(2):113-21.

6. “Behaviorism: Classic Studies” (Casper, Wyo: Endeavor Books/Mountain States Litho, 2009).

7. Journal of LGBT Issues in Counseling. 2008;2(2):126-58.

8. Genet Psychol Monogr. 1967;75(1):43-88.

9. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.

10. “Parental Monitoring of Adolescents: Current Perspectives for Researchers and Practitioners” (New York: Columbia University Press, 2010).

11. AIDS Behav. 2014 Aug;18(8):1604-14.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

Two years ago, a mother of one of my patients asked me for advice. She knew that her daughter identified as lesbian, and she was fully supportive. One day, her daughter wanted to go to a sleepover at a female friend’s house. Her first reaction was to say yes, but then she had second thoughts: If her daughter were straight, and this friend were male, she would not allow her to go because of the potential for sexual activity. When she told her daughter she could not attend the sleepover, her daughter accused her of not letting her go because of her sexual orientation. And now, the dilemma: In her effort to be fair and consistent with her values, the mother is being accused of discrimination. What should she do?

Parents play an irreplaceable role in the life of any teen, especially in the lives of teens that identify as lesbian, gay, bisexual, or transgender (LGBT). But many LGBT youth face serious challenges with their parents. They face the potential of parental rejection of their sexual or gender identity. At the very worst, teens may face homelessness if they come out to homophobic parents.¹ Youth whose parents are accepting, nevertheless, are less likely to have mental health problems or engage in substance use.²

As a clinical provider for children and adolescents, caregivers will ask you for advice on how to address parenting challenges. Because LGBT youth are at risk for many adverse health outcomes, and parental support is paramount in preventing them, this is an opportunity for you to help this vulnerable population.

If parents ask you how to be supportive of their LGBT children, here are some recommendations, which are based on an intervention by colleagues at the University of Utah:³

1. Let their affection show. Receiving news that a child is LGBT can be emotionally intense for parents.⁴ Because of this emotional intensity, parents may react negatively and neglect to show their love for their child, which is what the child is seeking. Parents showing affection is the first step in supporting their LGBT child. Remind parents to tell their child that they love them no matter what.

2. Avoid rejecting behaviors. This is sometimes hard, because some forms of rejection can be quite subtle. Avoid saying anything that may indicate a negative view of LGBT people, even if it is not intended. For example, saying that something is “gay” may seem innocent enough, but it sends the message that being gay is something to be ashamed of.

3. Express their pain away from their child. Evidence shows that minimizing a child’s exposure to parental conflict and stress is associated with better coping with these devastating events.⁵ Parents should avoid telling their children that news of their sexual orientation or gender identity upsets them, as this is another form of rejecting behavior.

4. Do good before they feel good. Previous studies suggest that changes in behavior can occur even though a person may feel otherwise.⁶ Negative feelings about a child’s sexual orientation or gender identity can last months or years.⁷ It’s okay to have these feelings, but showing support such as telling their child how they still love them can ultimately lead to acceptance.

Although it is important for parents to accept their child, it is only half the battle. If you remember Baumrind’s theory on parenting, there are two sides of parenting. The first side involves parents showing their affection, love, and support for their children, which I described earlier. The other side involves managing a child’s behaviors, whether parents create an environment that makes it difficult to engage in behaviors they disapprove of or teach their children how to make the right decision.⁸ Many LGBT youth engage in risky behaviors because it’s a way of coping in a homophobic environment. The parents’ job is to teach their children healthier coping strategies.

Research on this aspect of parenting in LGBT youth is still at its infancy, and some of it is not reassuring. One important behavior, parental monitoring, which is “a set of correlated parenting behaviors involving attention to and tracking of the child’s whereabouts, activities, and adaptations,”⁹ can prevent conduct disorders, substance use, and mental health problems in the typical teenager.¹⁰ Unfortunately, we don’t find the same results for sexual minorities. One study suggests that parental monitoring may not prevent high-risk sexual behavior for young gay males, even if the parent is aware of the young man’s sexual orientation.¹¹

This doesn’t mean that parental monitoring isn’t helpful. This just means that parenting LGBT youth is different than parenting heterosexual youth. It’s not enough for parents to just accept their child’s sexual orientation. They also must help them make the right decisions taking into consideration the effect of stigma and discrimination on sexual minorities. There are a couple of things you can suggest to your parents to help them raise their LGBT children:

1. Be proactive. Join organizations that support parents of LGBT youth such as Parents, Families, and Friends of Lesbians and Gays (PFLAG). Also, parents must be aware of their children’s behavior. If they are acting depressed, seek help. Having depression or anxiety increases the chances of engaging in risky behaviors, so the earlier parents address this, the better.

2. Make their child know what their views are on high risk-behaviors, such as substance use or having unprotected sex. They need to communicate their expectations clearly. If parents believe that drinking alcohol before the legal age is wrong, they should clearly let their children know that.

3. Make it easier for their child to tell parents what’s going on in their lives. Parents have to gain their children’s trust, be accessible (don’t answer texts while talking to them!), and be an active listener. LGBT youth may not ask parents for advice because they feel that because their parents are straight or cisgender, their life experiences do not apply. Being a member of an organization like PLFAG can be helpful, because parents can ask other parents who have experience raising LGBT youth for advice that works.

4. If parents’ children do something wrong, they should talk to them about how their actions were risky. Children will listen to parents if they view their parenting as legitimate and fair, which can only happen if there is a strong parent-child relationship. Being supportive of a child’s sexual orientation or gender identity is key here. And for the next time, it’s always good to role-play a scenario (for example, what to do if someone tries to make them drink at a party).

Parents of LGBT youth face many challenges. You can help these parents by encouraging them to accept and support their child’s sexual orientation or gender identity and provide parenting strategies relevant for LGBT youth. Most important of all, encourage them to seek support through organizations like PFLAG. With this support, parents can encourage healthy development in LGBT youth.

Resources for parents of LGBT youth

• The Centers for Disease Control and Prevention (CDC) has information on the health of LGBT Youth and advice on parental monitoring in general.

• The Family Acceptance Project is a project researching ways to improve parent-child relationships in LGBT Youth.

• PFLAG is an organization that provides support for families of LGBT youth.

• Lead with Love is a film about how various types of families react to their children coming out to them.

References

1. J Sex Res. 2004 Nov;41(4):329-42.

2. Aust N Z J Psychiatry. 2010 Sep;44(9):774-83.

3. Huebner D. “Leading with Love: Interventions to Support Families of Lesbian, Gay, and Bisexual Adolescents,” The Register Report, Vol. 39. National Register of Health Service Psychologists, Spring 2013.

4. J GLBT Fam Stud. 2014 Jan;10(1-2):36-57.

5. Prof Psychol Res Pr. 2008 Apr;39(2):113-21.

6. “Behaviorism: Classic Studies” (Casper, Wyo: Endeavor Books/Mountain States Litho, 2009).

7. Journal of LGBT Issues in Counseling. 2008;2(2):126-58.

8. Genet Psychol Monogr. 1967;75(1):43-88.

9. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.

10. “Parental Monitoring of Adolescents: Current Perspectives for Researchers and Practitioners” (New York: Columbia University Press, 2010).

11. AIDS Behav. 2014 Aug;18(8):1604-14.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

Clinical question: How does parental perception of overnight pediatric inpatient care affect the overall patient experience?

Background: Restrictions on resident duty hours have become progressively more stringent as attention to the effects of resident fatigue on patient safety has increased. In 2011, the Accreditation Council for Graduate Medical Education (ACGME) limited total weekly duty hours to 80 and reduced shifts for junior trainees to a maximum of 16 hours. As a result, a majority of teaching hospitals have instituted “night float,” or night team models, for overnight coverage of pediatric inpatients. The rapid adoption of night float inpatient coverage models has raised concerns about training residents in a structure that may not foster patient ownership and may promote shift worker mentality. Although communication between healthcare providers and patients/caregivers is known to be a key driver of patient satisfaction, little is known about the quality of communication overnight in the era of night float teams.

Study design: Prospective cohort study utilizing survey methodology.

Setting: Two general pediatric units at a 395-bed, urban, freestanding children’s teaching hospital.

Synopsis: A randomly selected subset of children (0-17 years) with English-speaking parents/caregivers admitted to two general pediatric units was studied over an 18-month period. Both general pediatric and subspecialty service patients, including adolescent, immunology, hematology, and rheumatology, were included. Researchers administered written surveys on weekday (Monday-Thursday) evenings prior to discharge, and surveys were collected either later that evening or in the morning. The surveys included 29 questions that used a five-point Likert scale to assess communication and experience.

These questions covered the following constructs:

1. Parent understanding of the medical plan;
2. Parent communication and experience with nighttime doctors;
3. Parent communication and experience with nighttime nurses;
4. Parent perceptions of nighttime interactions between doctors and nurses; and
5. Parent overall experience of care during hospitalization.

An open question addressing whether parents had anything else to share about communication during the hospitalization was included. The primary outcome measure was the so-called “top-box” rating of overall experience of care during the hospitalization (from construct five). This outcome was dichotomous based on whether the parent had given the highest rating or not for all five questions in that construct (either “excellent” or “strongly agree”).

A top-box rating of overall experience of care was found to be associated with high mean construct scores regarding communication and experience with doctors (4.85) and nurses (4.87). Top-box overall experience ratings were also associated with top ratings for coordination between daytime and nighttime nurses and for teamwork between nighttime doctors and nurses. Multivariable analysis showed that parents’ rating of direct communications with doctors and nurses and perceived teamwork and communication between doctors and nurses were significant predictors of top-box overall experience.

Bottom line: Parents’ perceptions of direct communications with nighttime doctors and nurses and their perceived teamwork and communication were strong predictors of overall experience of care during pediatric hospitalization.

Citation: Khan A, Rogers JE, Melvin P, et al. Physician and nurse nighttime communication and parents’ hospital experience. Pediatrics. 2015;136(5):e1249-1258.

Clinical question: How does parental perception of overnight pediatric inpatient care affect the overall patient experience?

Background: Restrictions on resident duty hours have become progressively more stringent as attention to the effects of resident fatigue on patient safety has increased. In 2011, the Accreditation Council for Graduate Medical Education (ACGME) limited total weekly duty hours to 80 and reduced shifts for junior trainees to a maximum of 16 hours. As a result, a majority of teaching hospitals have instituted “night float,” or night team models, for overnight coverage of pediatric inpatients. The rapid adoption of night float inpatient coverage models has raised concerns about training residents in a structure that may not foster patient ownership and may promote shift worker mentality. Although communication between healthcare providers and patients/caregivers is known to be a key driver of patient satisfaction, little is known about the quality of communication overnight in the era of night float teams.

Study design: Prospective cohort study utilizing survey methodology.

Setting: Two general pediatric units at a 395-bed, urban, freestanding children’s teaching hospital.

Synopsis: A randomly selected subset of children (0-17 years) with English-speaking parents/caregivers admitted to two general pediatric units was studied over an 18-month period. Both general pediatric and subspecialty service patients, including adolescent, immunology, hematology, and rheumatology, were included. Researchers administered written surveys on weekday (Monday-Thursday) evenings prior to discharge, and surveys were collected either later that evening or in the morning. The surveys included 29 questions that used a five-point Likert scale to assess communication and experience.

These questions covered the following constructs:

1. Parent understanding of the medical plan;
2. Parent communication and experience with nighttime doctors;
3. Parent communication and experience with nighttime nurses;
4. Parent perceptions of nighttime interactions between doctors and nurses; and
5. Parent overall experience of care during hospitalization.

An open question addressing whether parents had anything else to share about communication during the hospitalization was included. The primary outcome measure was the so-called “top-box” rating of overall experience of care during the hospitalization (from construct five). This outcome was dichotomous based on whether the parent had given the highest rating or not for all five questions in that construct (either “excellent” or “strongly agree”).

A top-box rating of overall experience of care was found to be associated with high mean construct scores regarding communication and experience with doctors (4.85) and nurses (4.87). Top-box overall experience ratings were also associated with top ratings for coordination between daytime and nighttime nurses and for teamwork between nighttime doctors and nurses. Multivariable analysis showed that parents’ rating of direct communications with doctors and nurses and perceived teamwork and communication between doctors and nurses were significant predictors of top-box overall experience.

Bottom line: Parents’ perceptions of direct communications with nighttime doctors and nurses and their perceived teamwork and communication were strong predictors of overall experience of care during pediatric hospitalization.

Citation: Khan A, Rogers JE, Melvin P, et al. Physician and nurse nighttime communication and parents’ hospital experience. Pediatrics. 2015;136(5):e1249-1258.

Clinical question: How does parental perception of overnight pediatric inpatient care affect the overall patient experience?

Background: Restrictions on resident duty hours have become progressively more stringent as attention to the effects of resident fatigue on patient safety has increased. In 2011, the Accreditation Council for Graduate Medical Education (ACGME) limited total weekly duty hours to 80 and reduced shifts for junior trainees to a maximum of 16 hours. As a result, a majority of teaching hospitals have instituted “night float,” or night team models, for overnight coverage of pediatric inpatients. The rapid adoption of night float inpatient coverage models has raised concerns about training residents in a structure that may not foster patient ownership and may promote shift worker mentality. Although communication between healthcare providers and patients/caregivers is known to be a key driver of patient satisfaction, little is known about the quality of communication overnight in the era of night float teams.

Study design: Prospective cohort study utilizing survey methodology.

Setting: Two general pediatric units at a 395-bed, urban, freestanding children’s teaching hospital.

Synopsis: A randomly selected subset of children (0-17 years) with English-speaking parents/caregivers admitted to two general pediatric units was studied over an 18-month period. Both general pediatric and subspecialty service patients, including adolescent, immunology, hematology, and rheumatology, were included. Researchers administered written surveys on weekday (Monday-Thursday) evenings prior to discharge, and surveys were collected either later that evening or in the morning. The surveys included 29 questions that used a five-point Likert scale to assess communication and experience.

These questions covered the following constructs:

1. Parent understanding of the medical plan;
2. Parent communication and experience with nighttime doctors;
3. Parent communication and experience with nighttime nurses;
4. Parent perceptions of nighttime interactions between doctors and nurses; and
5. Parent overall experience of care during hospitalization.

An open question addressing whether parents had anything else to share about communication during the hospitalization was included. The primary outcome measure was the so-called “top-box” rating of overall experience of care during the hospitalization (from construct five). This outcome was dichotomous based on whether the parent had given the highest rating or not for all five questions in that construct (either “excellent” or “strongly agree”).

A top-box rating of overall experience of care was found to be associated with high mean construct scores regarding communication and experience with doctors (4.85) and nurses (4.87). Top-box overall experience ratings were also associated with top ratings for coordination between daytime and nighttime nurses and for teamwork between nighttime doctors and nurses. Multivariable analysis showed that parents’ rating of direct communications with doctors and nurses and perceived teamwork and communication between doctors and nurses were significant predictors of top-box overall experience.

Bottom line: Parents’ perceptions of direct communications with nighttime doctors and nurses and their perceived teamwork and communication were strong predictors of overall experience of care during pediatric hospitalization.

Citation: Khan A, Rogers JE, Melvin P, et al. Physician and nurse nighttime communication and parents’ hospital experience. Pediatrics. 2015;136(5):e1249-1258.

Prescription medications

Photo courtesy of the CDC

ORLANDO, FL—In a small study, the cholesterol-lowering medication simvastatin reduced the frequency of vaso-occlusive pain in adults and children with sickle cell disease (SCD).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain after 3 months of treatment with simvastatin.

There was a slight overall decrease in the intensity of pain as well, but this was not statistically significant.

Still, investigators observed a decrease in biomarkers of inflammation and said the drug appeared to be safe for this patient population.

The team believes these preliminary data suggest the need to conduct a larger, randomized trial of simvastatin in SCD.

Carolyn C. Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California, presented the data at the 2015 ASH Annual Meeting (abstract 545).*

“Vaso-occlusive pain is a clinical hallmark and major cause of morbidity in sickle cell disease,” Dr Hoppe said. “Triggered by polymerization and hemolysis, vaso-occlusion involves multiple pathways.”

Similarly, although statins are best known for their cholesterol-inhibiting ability, they also inhibit oxidative stress and inflammation.

With this in mind, Dr Hoppe and her colleagues previously tested simvastatin in a phase 1 study of SCD patients who were 13 years of age or older.

The investigators found the safety profile to be acceptable, and they observed an improvement in biomarkers of inflammation. So they decided to carry out the current study.

This was a single-center, uncontrolled trial that enrolled SCD patients ages 10 and older. They received once-daily oral simvastatin (40 mg) for 3 months.

The primary outcome measure was the frequency and intensity of vaso-occlusive pain, as recorded by daily electronic pain diaries, before and after simvastatin treatment.

Clinical laboratory studies and plasma biomarkers were evaluated at baseline, at 0.5, 1, 2, and 3 months during treatment, as well as 1 month after the discontinuation of simvastatin.

Results

Nineteen patients completed the study. They had a mean age of 19 (range, 10-34), and 13 were female. Seventeen had HbSS genotype, and 2 had S/β0 thalassemia. Ten patients were receiving hydroxyurea.

The simvastatin adherence rate was 85%, and the adherence to using the daily pain diary was 73%.

Dr Hoppe said there were no new safety issues or drug-related adverse events in this trial. There was no myalgia or myopathy. One subject did experience transient facial swelling that may have been drug-related.

The patients’ total cholesterol decreased by 20% from baseline. There was a significant decrease in both LDL and HDL cholesterol (P<0.001 for both).

Creatinine kinase remained stable during treatment, as did hemoglobin levels.

Dr Hoppe noted that the study was not designed to include an assessment of fetal hemoglobin, so she and her colleagues did not have data on that measure for all the patients, but the team did observe an increase in fetal hemoglobin levels from baseline among the patients who were receiving hydroxyurea.

The investigators observed a decrease from baseline in markers of hemolysis—absolute reticulocyte count (P=0.006) and total bilirubin (P=0.02).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain from baseline (P=0.005) and a 10% decrease in the intensity of pain (which was not significant).

There was a 59% decrease in hsCRP (P=0.003), an 18% decrease in sE-selectin (P=0.01), a 5% decrease in sICAM (P=0.03), and a 17% decrease in VEGF (P=0.05). There was no significant effect on plasma nitric oxide metabolites, sVCAM1, or P-selectin levels.

“These results are basically preliminary data to give clinical support for a larger, randomized trial of simvastatin to assess its clinical efficacy in SCD,” Dr Hoppe concluded.

She reported receiving research funding and consultancy payments from Eli Lilly and Company, and another investigator involved in this study is an employee of Pharmacyclics LLC.

*Data in the abstract differ from the data presented.

Prescription medications

Photo courtesy of the CDC

ORLANDO, FL—In a small study, the cholesterol-lowering medication simvastatin reduced the frequency of vaso-occlusive pain in adults and children with sickle cell disease (SCD).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain after 3 months of treatment with simvastatin.

There was a slight overall decrease in the intensity of pain as well, but this was not statistically significant.

Still, investigators observed a decrease in biomarkers of inflammation and said the drug appeared to be safe for this patient population.

The team believes these preliminary data suggest the need to conduct a larger, randomized trial of simvastatin in SCD.

Carolyn C. Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California, presented the data at the 2015 ASH Annual Meeting (abstract 545).*

“Vaso-occlusive pain is a clinical hallmark and major cause of morbidity in sickle cell disease,” Dr Hoppe said. “Triggered by polymerization and hemolysis, vaso-occlusion involves multiple pathways.”

Similarly, although statins are best known for their cholesterol-inhibiting ability, they also inhibit oxidative stress and inflammation.

With this in mind, Dr Hoppe and her colleagues previously tested simvastatin in a phase 1 study of SCD patients who were 13 years of age or older.

The investigators found the safety profile to be acceptable, and they observed an improvement in biomarkers of inflammation. So they decided to carry out the current study.

This was a single-center, uncontrolled trial that enrolled SCD patients ages 10 and older. They received once-daily oral simvastatin (40 mg) for 3 months.

The primary outcome measure was the frequency and intensity of vaso-occlusive pain, as recorded by daily electronic pain diaries, before and after simvastatin treatment.

Clinical laboratory studies and plasma biomarkers were evaluated at baseline, at 0.5, 1, 2, and 3 months during treatment, as well as 1 month after the discontinuation of simvastatin.

Results

Nineteen patients completed the study. They had a mean age of 19 (range, 10-34), and 13 were female. Seventeen had HbSS genotype, and 2 had S/β0 thalassemia. Ten patients were receiving hydroxyurea.

The simvastatin adherence rate was 85%, and the adherence to using the daily pain diary was 73%.

Dr Hoppe said there were no new safety issues or drug-related adverse events in this trial. There was no myalgia or myopathy. One subject did experience transient facial swelling that may have been drug-related.

The patients’ total cholesterol decreased by 20% from baseline. There was a significant decrease in both LDL and HDL cholesterol (P<0.001 for both).

Creatinine kinase remained stable during treatment, as did hemoglobin levels.

Dr Hoppe noted that the study was not designed to include an assessment of fetal hemoglobin, so she and her colleagues did not have data on that measure for all the patients, but the team did observe an increase in fetal hemoglobin levels from baseline among the patients who were receiving hydroxyurea.

The investigators observed a decrease from baseline in markers of hemolysis—absolute reticulocyte count (P=0.006) and total bilirubin (P=0.02).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain from baseline (P=0.005) and a 10% decrease in the intensity of pain (which was not significant).

There was a 59% decrease in hsCRP (P=0.003), an 18% decrease in sE-selectin (P=0.01), a 5% decrease in sICAM (P=0.03), and a 17% decrease in VEGF (P=0.05). There was no significant effect on plasma nitric oxide metabolites, sVCAM1, or P-selectin levels.

“These results are basically preliminary data to give clinical support for a larger, randomized trial of simvastatin to assess its clinical efficacy in SCD,” Dr Hoppe concluded.

She reported receiving research funding and consultancy payments from Eli Lilly and Company, and another investigator involved in this study is an employee of Pharmacyclics LLC.

*Data in the abstract differ from the data presented.

Prescription medications

Photo courtesy of the CDC

ORLANDO, FL—In a small study, the cholesterol-lowering medication simvastatin reduced the frequency of vaso-occlusive pain in adults and children with sickle cell disease (SCD).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain after 3 months of treatment with simvastatin.

There was a slight overall decrease in the intensity of pain as well, but this was not statistically significant.

Still, investigators observed a decrease in biomarkers of inflammation and said the drug appeared to be safe for this patient population.

The team believes these preliminary data suggest the need to conduct a larger, randomized trial of simvastatin in SCD.

Carolyn C. Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California, presented the data at the 2015 ASH Annual Meeting (abstract 545).*

“Vaso-occlusive pain is a clinical hallmark and major cause of morbidity in sickle cell disease,” Dr Hoppe said. “Triggered by polymerization and hemolysis, vaso-occlusion involves multiple pathways.”

Similarly, although statins are best known for their cholesterol-inhibiting ability, they also inhibit oxidative stress and inflammation.

With this in mind, Dr Hoppe and her colleagues previously tested simvastatin in a phase 1 study of SCD patients who were 13 years of age or older.

The investigators found the safety profile to be acceptable, and they observed an improvement in biomarkers of inflammation. So they decided to carry out the current study.

This was a single-center, uncontrolled trial that enrolled SCD patients ages 10 and older. They received once-daily oral simvastatin (40 mg) for 3 months.

The primary outcome measure was the frequency and intensity of vaso-occlusive pain, as recorded by daily electronic pain diaries, before and after simvastatin treatment.

Clinical laboratory studies and plasma biomarkers were evaluated at baseline, at 0.5, 1, 2, and 3 months during treatment, as well as 1 month after the discontinuation of simvastatin.

Results

Nineteen patients completed the study. They had a mean age of 19 (range, 10-34), and 13 were female. Seventeen had HbSS genotype, and 2 had S/β0 thalassemia. Ten patients were receiving hydroxyurea.

The simvastatin adherence rate was 85%, and the adherence to using the daily pain diary was 73%.

Dr Hoppe said there were no new safety issues or drug-related adverse events in this trial. There was no myalgia or myopathy. One subject did experience transient facial swelling that may have been drug-related.

The patients’ total cholesterol decreased by 20% from baseline. There was a significant decrease in both LDL and HDL cholesterol (P<0.001 for both).

Creatinine kinase remained stable during treatment, as did hemoglobin levels.

Dr Hoppe noted that the study was not designed to include an assessment of fetal hemoglobin, so she and her colleagues did not have data on that measure for all the patients, but the team did observe an increase in fetal hemoglobin levels from baseline among the patients who were receiving hydroxyurea.

The investigators observed a decrease from baseline in markers of hemolysis—absolute reticulocyte count (P=0.006) and total bilirubin (P=0.02).

Overall, there was a 46% decrease in the frequency of vaso-occlusive pain from baseline (P=0.005) and a 10% decrease in the intensity of pain (which was not significant).

There was a 59% decrease in hsCRP (P=0.003), an 18% decrease in sE-selectin (P=0.01), a 5% decrease in sICAM (P=0.03), and a 17% decrease in VEGF (P=0.05). There was no significant effect on plasma nitric oxide metabolites, sVCAM1, or P-selectin levels.

“These results are basically preliminary data to give clinical support for a larger, randomized trial of simvastatin to assess its clinical efficacy in SCD,” Dr Hoppe concluded.

She reported receiving research funding and consultancy payments from Eli Lilly and Company, and another investigator involved in this study is an employee of Pharmacyclics LLC.

*Data in the abstract differ from the data presented.

Ashok Deniz, PhD

Photo courtesy of The

Scripps Research Institute

New research shows how NPM1—a protein implicated in non-Hodgkin lymphoma, acute myelogenous leukemia, and other cancers—twists and morphs into different structures.

This protein has many functions and, when mutated, has been shown to interfere with cells’ normal tumor suppressing ability.

Previous research showed that a section of NPM1, called the N-terminal domain, doesn’t have a defined, folded structure.

Instead, the protein morphs between 2 forms: a 1-subunit disordered monomer and a 5-subunit folded pentamer.

Until now, the mechanism behind this transformation was unknown, but researchers believed this monomer-pentamer equilibrium could be important for the protein’s location and functioning in the cell.

Ashok Deniz, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues conducted the current study to shed light on how this transformation occurs. They reported their findings in Angewandte Chemie.

The researchers used a combination of 3 techniques to analyze NPM1—single-molecule biophysics, fluorescence resonance energy transfer, and circular dichroism.

These techniques revealed that NPM1’s transformation can proceed through more than one pathway. In one pathway, the transformation begins when the cell sends signals to attach phosphoryl groups to NPM1.

This phosphorylation prompts the ordered pentamer to become disordered and likely causes NPM1 to shuttle outside the cell’s nucleus. A meeting with a binding partner can mediate the reverse transformation to a pentamer.

However, when NPM1 does become a pentamer again under these conditions, which likely causes it to move back to the nucleolus, it takes a different path instead of just retracing its earlier steps.

The study also revealed many intermediate states between monomer and pentamer structures. And it showed that these states can be manipulated or “tuned” by changing conditions such as salt levels, phosphorylation, and partner binding, which may explain how cells regulate NPM1’s multiple functions.

The researchers said future studies could shed more light on the biological functions of these different structures and how they might be used in future cancer therapies.

“We’re studying basic biophysics, but we believe the complexity and rules we uncover for the physics of protein disorder and folding could one day also be used for better designs of therapeutics,” Dr Deniz said.

He and his colleagues also believe that combining the 3 techniques used in this study, plus a novel protein-labeling technique for single-molecule fluorescence, could be a useful strategy for studying other unstructured, intrinsically disordered proteins. 

Ashok Deniz, PhD

Photo courtesy of The

Scripps Research Institute

New research shows how NPM1—a protein implicated in non-Hodgkin lymphoma, acute myelogenous leukemia, and other cancers—twists and morphs into different structures.

This protein has many functions and, when mutated, has been shown to interfere with cells’ normal tumor suppressing ability.

Previous research showed that a section of NPM1, called the N-terminal domain, doesn’t have a defined, folded structure.

Instead, the protein morphs between 2 forms: a 1-subunit disordered monomer and a 5-subunit folded pentamer.

Until now, the mechanism behind this transformation was unknown, but researchers believed this monomer-pentamer equilibrium could be important for the protein’s location and functioning in the cell.

Ashok Deniz, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues conducted the current study to shed light on how this transformation occurs. They reported their findings in Angewandte Chemie.

The researchers used a combination of 3 techniques to analyze NPM1—single-molecule biophysics, fluorescence resonance energy transfer, and circular dichroism.

These techniques revealed that NPM1’s transformation can proceed through more than one pathway. In one pathway, the transformation begins when the cell sends signals to attach phosphoryl groups to NPM1.

This phosphorylation prompts the ordered pentamer to become disordered and likely causes NPM1 to shuttle outside the cell’s nucleus. A meeting with a binding partner can mediate the reverse transformation to a pentamer.

However, when NPM1 does become a pentamer again under these conditions, which likely causes it to move back to the nucleolus, it takes a different path instead of just retracing its earlier steps.

The study also revealed many intermediate states between monomer and pentamer structures. And it showed that these states can be manipulated or “tuned” by changing conditions such as salt levels, phosphorylation, and partner binding, which may explain how cells regulate NPM1’s multiple functions.

The researchers said future studies could shed more light on the biological functions of these different structures and how they might be used in future cancer therapies.

“We’re studying basic biophysics, but we believe the complexity and rules we uncover for the physics of protein disorder and folding could one day also be used for better designs of therapeutics,” Dr Deniz said.

He and his colleagues also believe that combining the 3 techniques used in this study, plus a novel protein-labeling technique for single-molecule fluorescence, could be a useful strategy for studying other unstructured, intrinsically disordered proteins. 

Ashok Deniz, PhD

Photo courtesy of The

Scripps Research Institute

New research shows how NPM1—a protein implicated in non-Hodgkin lymphoma, acute myelogenous leukemia, and other cancers—twists and morphs into different structures.

This protein has many functions and, when mutated, has been shown to interfere with cells’ normal tumor suppressing ability.

Previous research showed that a section of NPM1, called the N-terminal domain, doesn’t have a defined, folded structure.

Instead, the protein morphs between 2 forms: a 1-subunit disordered monomer and a 5-subunit folded pentamer.

Until now, the mechanism behind this transformation was unknown, but researchers believed this monomer-pentamer equilibrium could be important for the protein’s location and functioning in the cell.

Ashok Deniz, PhD, of The Scripps Research Institute in La Jolla, California, and his colleagues conducted the current study to shed light on how this transformation occurs. They reported their findings in Angewandte Chemie.

The researchers used a combination of 3 techniques to analyze NPM1—single-molecule biophysics, fluorescence resonance energy transfer, and circular dichroism.

These techniques revealed that NPM1’s transformation can proceed through more than one pathway. In one pathway, the transformation begins when the cell sends signals to attach phosphoryl groups to NPM1.

This phosphorylation prompts the ordered pentamer to become disordered and likely causes NPM1 to shuttle outside the cell’s nucleus. A meeting with a binding partner can mediate the reverse transformation to a pentamer.

However, when NPM1 does become a pentamer again under these conditions, which likely causes it to move back to the nucleolus, it takes a different path instead of just retracing its earlier steps.

The study also revealed many intermediate states between monomer and pentamer structures. And it showed that these states can be manipulated or “tuned” by changing conditions such as salt levels, phosphorylation, and partner binding, which may explain how cells regulate NPM1’s multiple functions.

The researchers said future studies could shed more light on the biological functions of these different structures and how they might be used in future cancer therapies.

“We’re studying basic biophysics, but we believe the complexity and rules we uncover for the physics of protein disorder and folding could one day also be used for better designs of therapeutics,” Dr Deniz said.

He and his colleagues also believe that combining the 3 techniques used in this study, plus a novel protein-labeling technique for single-molecule fluorescence, could be a useful strategy for studying other unstructured, intrinsically disordered proteins. 

Antihemophilic factor

An antihemophilic factor that was recently approved in the US has met the primary endpoint of a phase 3 study, according to the product’s maker, Baxalta.

The product is Adynovate, a recombinant pegylated factor VIII (FVIII) treatment based on the full-length Advate molecule.

The study enrolled patients younger than 12 years of age who had severe hemophilia A. And, thus far, none of these patients has developed inhibitors to Adynovate, which was the study’s primary endpoint.

Adynovate also proved effective for preventing bleeds in some patients and did not appear to produce any serious adverse events.

Adynovate was approved in the US last month for use as routine prophylaxis and on-demand treatment and control of bleeding episodes in hemophilia A patients age 12 and older.

Baxalta said the phase 3 data will form the basis of a US filing for a pediatric indication in early 2016.

The study was designed to assess the safety and immunogenicity of Adynovate in young, previously treated patients with severe hemophilia A. The study enrolled 73 such patients.

Researchers assessed the hemostatic efficacy of Adynovate as prophylaxis and for treatment of bleeding episodes. All patients received prophylactic Adynovate treatment (a median of 1.9 infusions per week) and were followed for 6 months.

The study’s primary endpoint was met, as no patients developed inhibitory antibodies to the drug. In addition, no treatment-related serious adverse events were reported.

About 73% of patients had no joint bleeds while on treatment, and about 38% had no bleeds of any kind.

The median annualized bleeding rate among patients treated with Adynovate was 2.0 (range, 0-49.8), and the mean was 3.0, which is comparable to the rates seen in adults treated with the product.

“These initial efficacy and safety findings indicate a potentially valuable role for Adynovate to treat pediatric patients with hemophilia A, with data consistent with what was reported in clinical studies among adult patients,” said John Orloff, MD, head of research & development and chief scientific officer at Baxalta.

With these results, the company plans to file for marketing authorization in Europe and aims to file for a pediatric indication in the US in early 2016.

Adynovate is currently under regulatory review in Japan, Canada, and Switzerland. Baxalta plans to present the complete data from this study at a congress in 2016.

Antihemophilic factor

An antihemophilic factor that was recently approved in the US has met the primary endpoint of a phase 3 study, according to the product’s maker, Baxalta.

The product is Adynovate, a recombinant pegylated factor VIII (FVIII) treatment based on the full-length Advate molecule.

The study enrolled patients younger than 12 years of age who had severe hemophilia A. And, thus far, none of these patients has developed inhibitors to Adynovate, which was the study’s primary endpoint.

Adynovate also proved effective for preventing bleeds in some patients and did not appear to produce any serious adverse events.

Adynovate was approved in the US last month for use as routine prophylaxis and on-demand treatment and control of bleeding episodes in hemophilia A patients age 12 and older.

Baxalta said the phase 3 data will form the basis of a US filing for a pediatric indication in early 2016.

The study was designed to assess the safety and immunogenicity of Adynovate in young, previously treated patients with severe hemophilia A. The study enrolled 73 such patients.

Researchers assessed the hemostatic efficacy of Adynovate as prophylaxis and for treatment of bleeding episodes. All patients received prophylactic Adynovate treatment (a median of 1.9 infusions per week) and were followed for 6 months.

The study’s primary endpoint was met, as no patients developed inhibitory antibodies to the drug. In addition, no treatment-related serious adverse events were reported.

About 73% of patients had no joint bleeds while on treatment, and about 38% had no bleeds of any kind.

The median annualized bleeding rate among patients treated with Adynovate was 2.0 (range, 0-49.8), and the mean was 3.0, which is comparable to the rates seen in adults treated with the product.

“These initial efficacy and safety findings indicate a potentially valuable role for Adynovate to treat pediatric patients with hemophilia A, with data consistent with what was reported in clinical studies among adult patients,” said John Orloff, MD, head of research & development and chief scientific officer at Baxalta.

With these results, the company plans to file for marketing authorization in Europe and aims to file for a pediatric indication in the US in early 2016.

Adynovate is currently under regulatory review in Japan, Canada, and Switzerland. Baxalta plans to present the complete data from this study at a congress in 2016.

Antihemophilic factor

An antihemophilic factor that was recently approved in the US has met the primary endpoint of a phase 3 study, according to the product’s maker, Baxalta.

The product is Adynovate, a recombinant pegylated factor VIII (FVIII) treatment based on the full-length Advate molecule.

The study enrolled patients younger than 12 years of age who had severe hemophilia A. And, thus far, none of these patients has developed inhibitors to Adynovate, which was the study’s primary endpoint.

Adynovate also proved effective for preventing bleeds in some patients and did not appear to produce any serious adverse events.

Adynovate was approved in the US last month for use as routine prophylaxis and on-demand treatment and control of bleeding episodes in hemophilia A patients age 12 and older.

Baxalta said the phase 3 data will form the basis of a US filing for a pediatric indication in early 2016.

The study was designed to assess the safety and immunogenicity of Adynovate in young, previously treated patients with severe hemophilia A. The study enrolled 73 such patients.

Researchers assessed the hemostatic efficacy of Adynovate as prophylaxis and for treatment of bleeding episodes. All patients received prophylactic Adynovate treatment (a median of 1.9 infusions per week) and were followed for 6 months.

The study’s primary endpoint was met, as no patients developed inhibitory antibodies to the drug. In addition, no treatment-related serious adverse events were reported.

About 73% of patients had no joint bleeds while on treatment, and about 38% had no bleeds of any kind.

The median annualized bleeding rate among patients treated with Adynovate was 2.0 (range, 0-49.8), and the mean was 3.0, which is comparable to the rates seen in adults treated with the product.

“These initial efficacy and safety findings indicate a potentially valuable role for Adynovate to treat pediatric patients with hemophilia A, with data consistent with what was reported in clinical studies among adult patients,” said John Orloff, MD, head of research & development and chief scientific officer at Baxalta.

With these results, the company plans to file for marketing authorization in Europe and aims to file for a pediatric indication in the US in early 2016.

Adynovate is currently under regulatory review in Japan, Canada, and Switzerland. Baxalta plans to present the complete data from this study at a congress in 2016.