Geriatrics

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

CASE Fixated on health and nutrition

At the insistence of her daughter, Ms. L, age 75, presents to the emergency department (ED) for self-neglect and severe weight loss, with a body mass index (BMI) of 13.5 kg/m² (normal: 18.5 to 24.9 kg/m²). When asked why she is in the ED, Ms. L says she doesn’t know. She attributes her significant weight loss (approximately 20 pounds in the last few months) to gastroesophageal reflux disease (GERD). She constantly worries about her esophagus. She had been diagnosed with esophageal dysphagia 7 years ago after undergoing radiofrequency ablation for esophageal cancer. Ms. L fixates on the negative effects certain foods and ingredients might have on her stomach and esophagus.

Following transfer from the ED, Ms. L is involuntarily admitted to our inpatient unit. Although she acknowledges weight loss, she minimizes the severity of her illness and indicates she would like to gain weight, but only by eating healthy foods she is comfortable with, including kale, quinoa, and vegetables. Ms. L says that she has always been interested in “healthful foods” and that she “loves sugar,” but “it’s bad for you,” mentioning that “sugar fuels cancer.” She has daily thoughts about sugar causing cancer. Ms. L also mentions that she stopped eating flour, sugar, fried food, and oils because those foods affect her “stomach acid” and cause “pimples on my face and weight loss.” While in the inpatient unit, Ms. L requests a special diet and demands to know the origin and ingredients of the foods she is offered. She emphasizes that her esophageal cancer diagnosis and dysphagia exacerbate worries that certain foods cause cancer, and wants to continue her diet restrictions. Nonetheless, she says she wants to get healthy, and denies an intense fear of gaining weight or feeling fat.

HISTORY Multiple psychiatric diagnoses

Ms. L lives alone and enjoys spending time with her grandchildren, visiting museums, and listening to classical music. However, her family, social workers, and records from a previous psychiatric hospitalization reveal that Ms. L has a history of psychiatric illness and fears regarding certain types of foods for much of her adult life. Ms. L’s family also described a range of compulsive behaviors, including shoplifting, hoarding art, multiple plastic surgeries, and phases where Ms. L ate only frozen yogurt without sugar.

Ms. L’s daughter reported that Ms. L had seen a psychologist in the late 1990s for depression and had been diagnosed with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder in the early 2000s. In 2006, during a depressive episode after her divorce, Ms. L had a suicide attempt with pills and alcohol, and was hospitalized. Records from that stay described a history of mood dysregulation with fears regarding food and nutrition. Ms. L was treated with aripiprazole 5 mg/d. A trial of trazodone 25 mg/d did not have any effect. When discharged, she was receiving lamotrigine 100 mg/d. However, her daughter believes she stopped taking all psychiatric medications shortly after discharge.

Her daughter says that in the past 2 years, Ms. L has seen multiple doctors for treatment of somatic gastrointestinal (GI) complaints. A 2018 note from a social worker indicated that Ms. L endorsed taking >80 supplements per day and constantly researched nutrition online. In the months leading to her current hospitalization, Ms. L suffered from severe self-neglect and fear regarding foods she felt were not healthy for her. She had stopped leaving her apartment.

Continue to: EVALUATION Poor insight, normal lab results...

EVALUATION Poor insight, normal lab results

During her evaluation, Ms. L appears cachectic and frail. She has a heavily constricted affect and is guarded, dismissive, and vague. Although her thought processes are linear and goal-directed, her insight into her condition is extremely poor and she appears surprised when clinicians inform her that her self-neglect would lead to death. Instead, Ms. L insists she is eating healthily and demonstrates severe anxiety in relation to her GI symptoms.

Ms. L is oriented to person, place, and time. She scores 27/30 on the Montreal Cognitive Assessment, indicating normal cognition. She denies any depressive symptoms or suicidal intent. She does not appear to be internally preoccupied and denies having auditory or visual hallucinations or manic symptoms.

A neurologic examination reveals that her cranial nerves are normal, and cerebellar function, strength, and sensory testing are intact. Her gait is steady and she walks without a walker. Despite her severely low BMI and recent history of self-neglect, Ms. L’s laboratory results are remarkably normal and show no liver, metabolic, or electrolyte abnormalities, no signs of infection, and normal vitamin B12 levels. She has slightly elevated creatinine and blood urea nitrogen levels, but a normal glomerular filtration rate.

Her medical history is significant for squamous cell esophageal cancer, treated with radiofrequency ablation. Although Ms. L is constantly worried about the recurrence of cancer, pathology reports demonstrate no esophageal dysplasia. However, she does show evidence of an approximately 1 cm × 1 cm mild, noncircumferential esophageal stenosis, likely resulting from radio­frequency ablation.

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The authors’ observations

Several health- and physical symptom-related psychiatric disorders have overlapping features, which can complicate the differential diagnosis (Table 1¹). Ms. L presented to the ED with a severely low BMI of 13.5 kg/m², obsessions regarding specific types of food, and preoccupations regarding her esophagus. Despite her extensive psychiatric history (including intense fears regarding food), we ruled out a primary psychotic disorder because she did not describe auditory or visual hallucinations and never appeared internally preoccupied. While her BMI and persistent minimization of the extent of her disease meet criteria for anorexia nervosa, she denied body dysmorphia and did not have any fear of gaining weight.

A central element of Ms. L’s presentation was her anxiety regarding how certain types of foods impact her health as well as her anxieties regarding her esophagus. While Ms. L was in remission from esophageal cancer and had a diagnosis of esophageal dysphagia, these preoccupations and obsessions regarding how certain types of foods affect her esophagus drove her to self-neglect and thus represent pathologic thought processes out of proportion to her symptoms. Illness anxiety disorder was considered because Ms. L met many of its criteria: preoccupation with having a serious illness, disproportionate preoccupation with somatic symptoms if they are present, extreme anxiety over health, and performance of health-related behaviors.¹ However, illness anxiety disorder is a diagnosis of exclusion, and 1 criterion is that these symptoms cannot be explained by another mental disorder. We felt other diagnoses better fit Ms. L’s condition and ruled out illness anxiety disorder.

Ms. L’s long history of food and non-food–related obsessions and compulsions that interrupted her ability to perform daily activities were strongly suggestive for OCD. Additionally, her intense preoccupation, high level of anxiety, amount of time and energy spent seeking care for her esophagus and GERD symptoms, and the resulting significant disruption of daily life, met criteria for somatic symptom disorder (SSD). However, we did not believe that a diagnosis of OCD and SSD alone explained the entirety of Ms. L’s clinical picture. Despite ruling out anorexia nervosa, Ms. L nonetheless demonstrated disordered eating.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder in which patients restrict their diet and do not meet nutritional needs for any number of reasons, do not experience body dysmorphia, and do not fear weight gain.¹ A common feature of ARFID is a fear of negative consequences from eating specific types of food.² Table 2^1,2 summarizes additional clinical features of ARFID. Although ARFID is typically diagnosed in children and adolescents, particularly in individuals with autism with heightened sensory sensitivities, ARFID is also common among adult patients with GI disorders.³ In a retrospective chart review of 410 adults ages 18 to 90 (73% women) referred to a neurogastroenterology care center, 6.3% met the full criteria for ARFID and 17.3% had clinically significant avoidant or restrictive eating behaviors. Among patients with ARFID symptoms, 93% stated that a fear of GI symptoms was the driver of their avoidant or restrictive eating behaviors.² Patients with GI diseases often develop dietary control and avoidance coping mechanisms to alleviate their symptoms.⁴ These strategies can exacerbate health anxieties and have a detrimental effect on mental health.⁵ Patients with GI disorders have a high degree of comorbidity with affective disorders, including anxiety disorders.⁶ These trends may arise from hypervigilance and the need to gain control over physical symptoms.⁷ Feeling a need for control, actions driven by anxiety and fear, and the need for compensatory behaviors are cardinal features of OCD and eating disorders.⁸ Multiple studies have demonstrated comorbidities between irritable bowel syndrome and eating disorders,⁹ SSD,¹⁰ and OCD.¹¹ Taken together with observations that ARFID is also found in patients with GI disorders,² these findings demonstrate that patients with a history of GI disease are at high risk of developing extreme health anxieties and behavioral coping strategies that can lead to disordered eating.

The rise in “healthy” eating materials online—particularly on social media—has created an atmosphere in which misinformation regarding diet and health is common and widespread. For patients with OCD and a predisposition to health anxiety, such as Ms. L, searching online for nutrition information and healthy living habits can exacerbate food-related anxieties and can lead to a pathological drive for purity and health.¹²Although not included in DSM-5, orthorexia nervosa was identified in 1997 as a proposed eating disorder best characterized as an obsession with healthy eating with associated restrictive behaviors.¹³ Patients with this disorder are rarely focused on losing weight, and orthorexic eating behaviors have been associated with both SSD and OCD.^12,14 As in Ms. L’s case, patients with orthorexia nervosa demonstrate intrusive obsessions with nutrition, spend excessive amount of time researching nutrition, and fixate on food quality.¹² Throughout Ms. L’s hospitalization, even as her food-related magical thinking symptoms improved, she constantly informed her care team that she had been “eating healthily” even though she was severely cachectic. Patients with SSD and OCD prone to health anxieties are at risk of developing pathologic food beliefs and dangerous eating behaviors. These patients may benefit from psychoeducation regarding nutrition and media literacy, which are components of effective eating disorder programs.¹⁵

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Continue to: The authors' observations...

How do we approach the pharmacologic treatment of patients with co-occurring eating, somatic symptom, and anxiety disorders? Olanzapine facilitates recovery in children and adolescents with ARFID by promoting eating and weight gain, and decreasing symptoms of depression and anxiety.¹⁶ Patients with orthorexia nervosa also may benefit from treatment with olanzapine, which has decreased food-related fixations, magical thinking, and delusions regarding food.¹⁷ Further, orthorexic patients with ARFID have also been shown to respond to SSRIs due to those agents’ efficacy for treating intrusive thoughts, obsessions, and preoccupations from OCD and SSD.^18,19 Thus, treating Ms. L’s symptoms with olanzapine and fluoxetine targeted the intersection of several diagnoses on our differential. Olanzapine’s propensity to cause weight gain is favorable in this population, particularly patients such as Ms. L, who do not exhibit body dysmorphia or fear of gaining weight.

OUTCOME Weight gain and fewer fears

Ms. L is prescribed olanzapine 5 mg/d and fluoxetine 20 mg/d. She gains 20.6 pounds in 4 weeks. Importantly, she endorses fewer fears related to foods and expands her palate to include foods she previously considered to be unhealthy, including white bread and farm-raised salmon. Further, she spends less time thinking about food and says she has less anxiety regarding the recurrence of GI symptoms.

CASE Fixated on health and nutrition

At the insistence of her daughter, Ms. L, age 75, presents to the emergency department (ED) for self-neglect and severe weight loss, with a body mass index (BMI) of 13.5 kg/m² (normal: 18.5 to 24.9 kg/m²). When asked why she is in the ED, Ms. L says she doesn’t know. She attributes her significant weight loss (approximately 20 pounds in the last few months) to gastroesophageal reflux disease (GERD). She constantly worries about her esophagus. She had been diagnosed with esophageal dysphagia 7 years ago after undergoing radiofrequency ablation for esophageal cancer. Ms. L fixates on the negative effects certain foods and ingredients might have on her stomach and esophagus.

Following transfer from the ED, Ms. L is involuntarily admitted to our inpatient unit. Although she acknowledges weight loss, she minimizes the severity of her illness and indicates she would like to gain weight, but only by eating healthy foods she is comfortable with, including kale, quinoa, and vegetables. Ms. L says that she has always been interested in “healthful foods” and that she “loves sugar,” but “it’s bad for you,” mentioning that “sugar fuels cancer.” She has daily thoughts about sugar causing cancer. Ms. L also mentions that she stopped eating flour, sugar, fried food, and oils because those foods affect her “stomach acid” and cause “pimples on my face and weight loss.” While in the inpatient unit, Ms. L requests a special diet and demands to know the origin and ingredients of the foods she is offered. She emphasizes that her esophageal cancer diagnosis and dysphagia exacerbate worries that certain foods cause cancer, and wants to continue her diet restrictions. Nonetheless, she says she wants to get healthy, and denies an intense fear of gaining weight or feeling fat.

HISTORY Multiple psychiatric diagnoses

Ms. L lives alone and enjoys spending time with her grandchildren, visiting museums, and listening to classical music. However, her family, social workers, and records from a previous psychiatric hospitalization reveal that Ms. L has a history of psychiatric illness and fears regarding certain types of foods for much of her adult life. Ms. L’s family also described a range of compulsive behaviors, including shoplifting, hoarding art, multiple plastic surgeries, and phases where Ms. L ate only frozen yogurt without sugar.

Ms. L’s daughter reported that Ms. L had seen a psychologist in the late 1990s for depression and had been diagnosed with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder in the early 2000s. In 2006, during a depressive episode after her divorce, Ms. L had a suicide attempt with pills and alcohol, and was hospitalized. Records from that stay described a history of mood dysregulation with fears regarding food and nutrition. Ms. L was treated with aripiprazole 5 mg/d. A trial of trazodone 25 mg/d did not have any effect. When discharged, she was receiving lamotrigine 100 mg/d. However, her daughter believes she stopped taking all psychiatric medications shortly after discharge.

Her daughter says that in the past 2 years, Ms. L has seen multiple doctors for treatment of somatic gastrointestinal (GI) complaints. A 2018 note from a social worker indicated that Ms. L endorsed taking >80 supplements per day and constantly researched nutrition online. In the months leading to her current hospitalization, Ms. L suffered from severe self-neglect and fear regarding foods she felt were not healthy for her. She had stopped leaving her apartment.

Continue to: EVALUATION Poor insight, normal lab results...

EVALUATION Poor insight, normal lab results

During her evaluation, Ms. L appears cachectic and frail. She has a heavily constricted affect and is guarded, dismissive, and vague. Although her thought processes are linear and goal-directed, her insight into her condition is extremely poor and she appears surprised when clinicians inform her that her self-neglect would lead to death. Instead, Ms. L insists she is eating healthily and demonstrates severe anxiety in relation to her GI symptoms.

Ms. L is oriented to person, place, and time. She scores 27/30 on the Montreal Cognitive Assessment, indicating normal cognition. She denies any depressive symptoms or suicidal intent. She does not appear to be internally preoccupied and denies having auditory or visual hallucinations or manic symptoms.

A neurologic examination reveals that her cranial nerves are normal, and cerebellar function, strength, and sensory testing are intact. Her gait is steady and she walks without a walker. Despite her severely low BMI and recent history of self-neglect, Ms. L’s laboratory results are remarkably normal and show no liver, metabolic, or electrolyte abnormalities, no signs of infection, and normal vitamin B12 levels. She has slightly elevated creatinine and blood urea nitrogen levels, but a normal glomerular filtration rate.

Her medical history is significant for squamous cell esophageal cancer, treated with radiofrequency ablation. Although Ms. L is constantly worried about the recurrence of cancer, pathology reports demonstrate no esophageal dysplasia. However, she does show evidence of an approximately 1 cm × 1 cm mild, noncircumferential esophageal stenosis, likely resulting from radio­frequency ablation.

[polldaddy:11079394]

The authors’ observations

Several health- and physical symptom-related psychiatric disorders have overlapping features, which can complicate the differential diagnosis (Table 1¹). Ms. L presented to the ED with a severely low BMI of 13.5 kg/m², obsessions regarding specific types of food, and preoccupations regarding her esophagus. Despite her extensive psychiatric history (including intense fears regarding food), we ruled out a primary psychotic disorder because she did not describe auditory or visual hallucinations and never appeared internally preoccupied. While her BMI and persistent minimization of the extent of her disease meet criteria for anorexia nervosa, she denied body dysmorphia and did not have any fear of gaining weight.

A central element of Ms. L’s presentation was her anxiety regarding how certain types of foods impact her health as well as her anxieties regarding her esophagus. While Ms. L was in remission from esophageal cancer and had a diagnosis of esophageal dysphagia, these preoccupations and obsessions regarding how certain types of foods affect her esophagus drove her to self-neglect and thus represent pathologic thought processes out of proportion to her symptoms. Illness anxiety disorder was considered because Ms. L met many of its criteria: preoccupation with having a serious illness, disproportionate preoccupation with somatic symptoms if they are present, extreme anxiety over health, and performance of health-related behaviors.¹ However, illness anxiety disorder is a diagnosis of exclusion, and 1 criterion is that these symptoms cannot be explained by another mental disorder. We felt other diagnoses better fit Ms. L’s condition and ruled out illness anxiety disorder.

Ms. L’s long history of food and non-food–related obsessions and compulsions that interrupted her ability to perform daily activities were strongly suggestive for OCD. Additionally, her intense preoccupation, high level of anxiety, amount of time and energy spent seeking care for her esophagus and GERD symptoms, and the resulting significant disruption of daily life, met criteria for somatic symptom disorder (SSD). However, we did not believe that a diagnosis of OCD and SSD alone explained the entirety of Ms. L’s clinical picture. Despite ruling out anorexia nervosa, Ms. L nonetheless demonstrated disordered eating.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder in which patients restrict their diet and do not meet nutritional needs for any number of reasons, do not experience body dysmorphia, and do not fear weight gain.¹ A common feature of ARFID is a fear of negative consequences from eating specific types of food.² Table 2^1,2 summarizes additional clinical features of ARFID. Although ARFID is typically diagnosed in children and adolescents, particularly in individuals with autism with heightened sensory sensitivities, ARFID is also common among adult patients with GI disorders.³ In a retrospective chart review of 410 adults ages 18 to 90 (73% women) referred to a neurogastroenterology care center, 6.3% met the full criteria for ARFID and 17.3% had clinically significant avoidant or restrictive eating behaviors. Among patients with ARFID symptoms, 93% stated that a fear of GI symptoms was the driver of their avoidant or restrictive eating behaviors.² Patients with GI diseases often develop dietary control and avoidance coping mechanisms to alleviate their symptoms.⁴ These strategies can exacerbate health anxieties and have a detrimental effect on mental health.⁵ Patients with GI disorders have a high degree of comorbidity with affective disorders, including anxiety disorders.⁶ These trends may arise from hypervigilance and the need to gain control over physical symptoms.⁷ Feeling a need for control, actions driven by anxiety and fear, and the need for compensatory behaviors are cardinal features of OCD and eating disorders.⁸ Multiple studies have demonstrated comorbidities between irritable bowel syndrome and eating disorders,⁹ SSD,¹⁰ and OCD.¹¹ Taken together with observations that ARFID is also found in patients with GI disorders,² these findings demonstrate that patients with a history of GI disease are at high risk of developing extreme health anxieties and behavioral coping strategies that can lead to disordered eating.

The rise in “healthy” eating materials online—particularly on social media—has created an atmosphere in which misinformation regarding diet and health is common and widespread. For patients with OCD and a predisposition to health anxiety, such as Ms. L, searching online for nutrition information and healthy living habits can exacerbate food-related anxieties and can lead to a pathological drive for purity and health.¹²Although not included in DSM-5, orthorexia nervosa was identified in 1997 as a proposed eating disorder best characterized as an obsession with healthy eating with associated restrictive behaviors.¹³ Patients with this disorder are rarely focused on losing weight, and orthorexic eating behaviors have been associated with both SSD and OCD.^12,14 As in Ms. L’s case, patients with orthorexia nervosa demonstrate intrusive obsessions with nutrition, spend excessive amount of time researching nutrition, and fixate on food quality.¹² Throughout Ms. L’s hospitalization, even as her food-related magical thinking symptoms improved, she constantly informed her care team that she had been “eating healthily” even though she was severely cachectic. Patients with SSD and OCD prone to health anxieties are at risk of developing pathologic food beliefs and dangerous eating behaviors. These patients may benefit from psychoeducation regarding nutrition and media literacy, which are components of effective eating disorder programs.¹⁵

[polldaddy:11079399]

Continue to: The authors' observations...

How do we approach the pharmacologic treatment of patients with co-occurring eating, somatic symptom, and anxiety disorders? Olanzapine facilitates recovery in children and adolescents with ARFID by promoting eating and weight gain, and decreasing symptoms of depression and anxiety.¹⁶ Patients with orthorexia nervosa also may benefit from treatment with olanzapine, which has decreased food-related fixations, magical thinking, and delusions regarding food.¹⁷ Further, orthorexic patients with ARFID have also been shown to respond to SSRIs due to those agents’ efficacy for treating intrusive thoughts, obsessions, and preoccupations from OCD and SSD.^18,19 Thus, treating Ms. L’s symptoms with olanzapine and fluoxetine targeted the intersection of several diagnoses on our differential. Olanzapine’s propensity to cause weight gain is favorable in this population, particularly patients such as Ms. L, who do not exhibit body dysmorphia or fear of gaining weight.

OUTCOME Weight gain and fewer fears

Ms. L is prescribed olanzapine 5 mg/d and fluoxetine 20 mg/d. She gains 20.6 pounds in 4 weeks. Importantly, she endorses fewer fears related to foods and expands her palate to include foods she previously considered to be unhealthy, including white bread and farm-raised salmon. Further, she spends less time thinking about food and says she has less anxiety regarding the recurrence of GI symptoms.

CASE Fixated on health and nutrition

At the insistence of her daughter, Ms. L, age 75, presents to the emergency department (ED) for self-neglect and severe weight loss, with a body mass index (BMI) of 13.5 kg/m² (normal: 18.5 to 24.9 kg/m²). When asked why she is in the ED, Ms. L says she doesn’t know. She attributes her significant weight loss (approximately 20 pounds in the last few months) to gastroesophageal reflux disease (GERD). She constantly worries about her esophagus. She had been diagnosed with esophageal dysphagia 7 years ago after undergoing radiofrequency ablation for esophageal cancer. Ms. L fixates on the negative effects certain foods and ingredients might have on her stomach and esophagus.

Following transfer from the ED, Ms. L is involuntarily admitted to our inpatient unit. Although she acknowledges weight loss, she minimizes the severity of her illness and indicates she would like to gain weight, but only by eating healthy foods she is comfortable with, including kale, quinoa, and vegetables. Ms. L says that she has always been interested in “healthful foods” and that she “loves sugar,” but “it’s bad for you,” mentioning that “sugar fuels cancer.” She has daily thoughts about sugar causing cancer. Ms. L also mentions that she stopped eating flour, sugar, fried food, and oils because those foods affect her “stomach acid” and cause “pimples on my face and weight loss.” While in the inpatient unit, Ms. L requests a special diet and demands to know the origin and ingredients of the foods she is offered. She emphasizes that her esophageal cancer diagnosis and dysphagia exacerbate worries that certain foods cause cancer, and wants to continue her diet restrictions. Nonetheless, she says she wants to get healthy, and denies an intense fear of gaining weight or feeling fat.

HISTORY Multiple psychiatric diagnoses

Ms. L lives alone and enjoys spending time with her grandchildren, visiting museums, and listening to classical music. However, her family, social workers, and records from a previous psychiatric hospitalization reveal that Ms. L has a history of psychiatric illness and fears regarding certain types of foods for much of her adult life. Ms. L’s family also described a range of compulsive behaviors, including shoplifting, hoarding art, multiple plastic surgeries, and phases where Ms. L ate only frozen yogurt without sugar.

Ms. L’s daughter reported that Ms. L had seen a psychologist in the late 1990s for depression and had been diagnosed with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder in the early 2000s. In 2006, during a depressive episode after her divorce, Ms. L had a suicide attempt with pills and alcohol, and was hospitalized. Records from that stay described a history of mood dysregulation with fears regarding food and nutrition. Ms. L was treated with aripiprazole 5 mg/d. A trial of trazodone 25 mg/d did not have any effect. When discharged, she was receiving lamotrigine 100 mg/d. However, her daughter believes she stopped taking all psychiatric medications shortly after discharge.

Her daughter says that in the past 2 years, Ms. L has seen multiple doctors for treatment of somatic gastrointestinal (GI) complaints. A 2018 note from a social worker indicated that Ms. L endorsed taking >80 supplements per day and constantly researched nutrition online. In the months leading to her current hospitalization, Ms. L suffered from severe self-neglect and fear regarding foods she felt were not healthy for her. She had stopped leaving her apartment.

Continue to: EVALUATION Poor insight, normal lab results...

EVALUATION Poor insight, normal lab results

During her evaluation, Ms. L appears cachectic and frail. She has a heavily constricted affect and is guarded, dismissive, and vague. Although her thought processes are linear and goal-directed, her insight into her condition is extremely poor and she appears surprised when clinicians inform her that her self-neglect would lead to death. Instead, Ms. L insists she is eating healthily and demonstrates severe anxiety in relation to her GI symptoms.

Ms. L is oriented to person, place, and time. She scores 27/30 on the Montreal Cognitive Assessment, indicating normal cognition. She denies any depressive symptoms or suicidal intent. She does not appear to be internally preoccupied and denies having auditory or visual hallucinations or manic symptoms.

A neurologic examination reveals that her cranial nerves are normal, and cerebellar function, strength, and sensory testing are intact. Her gait is steady and she walks without a walker. Despite her severely low BMI and recent history of self-neglect, Ms. L’s laboratory results are remarkably normal and show no liver, metabolic, or electrolyte abnormalities, no signs of infection, and normal vitamin B12 levels. She has slightly elevated creatinine and blood urea nitrogen levels, but a normal glomerular filtration rate.

Her medical history is significant for squamous cell esophageal cancer, treated with radiofrequency ablation. Although Ms. L is constantly worried about the recurrence of cancer, pathology reports demonstrate no esophageal dysplasia. However, she does show evidence of an approximately 1 cm × 1 cm mild, noncircumferential esophageal stenosis, likely resulting from radio­frequency ablation.

[polldaddy:11079394]

The authors’ observations

Several health- and physical symptom-related psychiatric disorders have overlapping features, which can complicate the differential diagnosis (Table 1¹). Ms. L presented to the ED with a severely low BMI of 13.5 kg/m², obsessions regarding specific types of food, and preoccupations regarding her esophagus. Despite her extensive psychiatric history (including intense fears regarding food), we ruled out a primary psychotic disorder because she did not describe auditory or visual hallucinations and never appeared internally preoccupied. While her BMI and persistent minimization of the extent of her disease meet criteria for anorexia nervosa, she denied body dysmorphia and did not have any fear of gaining weight.

A central element of Ms. L’s presentation was her anxiety regarding how certain types of foods impact her health as well as her anxieties regarding her esophagus. While Ms. L was in remission from esophageal cancer and had a diagnosis of esophageal dysphagia, these preoccupations and obsessions regarding how certain types of foods affect her esophagus drove her to self-neglect and thus represent pathologic thought processes out of proportion to her symptoms. Illness anxiety disorder was considered because Ms. L met many of its criteria: preoccupation with having a serious illness, disproportionate preoccupation with somatic symptoms if they are present, extreme anxiety over health, and performance of health-related behaviors.¹ However, illness anxiety disorder is a diagnosis of exclusion, and 1 criterion is that these symptoms cannot be explained by another mental disorder. We felt other diagnoses better fit Ms. L’s condition and ruled out illness anxiety disorder.

Ms. L’s long history of food and non-food–related obsessions and compulsions that interrupted her ability to perform daily activities were strongly suggestive for OCD. Additionally, her intense preoccupation, high level of anxiety, amount of time and energy spent seeking care for her esophagus and GERD symptoms, and the resulting significant disruption of daily life, met criteria for somatic symptom disorder (SSD). However, we did not believe that a diagnosis of OCD and SSD alone explained the entirety of Ms. L’s clinical picture. Despite ruling out anorexia nervosa, Ms. L nonetheless demonstrated disordered eating.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder in which patients restrict their diet and do not meet nutritional needs for any number of reasons, do not experience body dysmorphia, and do not fear weight gain.¹ A common feature of ARFID is a fear of negative consequences from eating specific types of food.² Table 2^1,2 summarizes additional clinical features of ARFID. Although ARFID is typically diagnosed in children and adolescents, particularly in individuals with autism with heightened sensory sensitivities, ARFID is also common among adult patients with GI disorders.³ In a retrospective chart review of 410 adults ages 18 to 90 (73% women) referred to a neurogastroenterology care center, 6.3% met the full criteria for ARFID and 17.3% had clinically significant avoidant or restrictive eating behaviors. Among patients with ARFID symptoms, 93% stated that a fear of GI symptoms was the driver of their avoidant or restrictive eating behaviors.² Patients with GI diseases often develop dietary control and avoidance coping mechanisms to alleviate their symptoms.⁴ These strategies can exacerbate health anxieties and have a detrimental effect on mental health.⁵ Patients with GI disorders have a high degree of comorbidity with affective disorders, including anxiety disorders.⁶ These trends may arise from hypervigilance and the need to gain control over physical symptoms.⁷ Feeling a need for control, actions driven by anxiety and fear, and the need for compensatory behaviors are cardinal features of OCD and eating disorders.⁸ Multiple studies have demonstrated comorbidities between irritable bowel syndrome and eating disorders,⁹ SSD,¹⁰ and OCD.¹¹ Taken together with observations that ARFID is also found in patients with GI disorders,² these findings demonstrate that patients with a history of GI disease are at high risk of developing extreme health anxieties and behavioral coping strategies that can lead to disordered eating.

The rise in “healthy” eating materials online—particularly on social media—has created an atmosphere in which misinformation regarding diet and health is common and widespread. For patients with OCD and a predisposition to health anxiety, such as Ms. L, searching online for nutrition information and healthy living habits can exacerbate food-related anxieties and can lead to a pathological drive for purity and health.¹²Although not included in DSM-5, orthorexia nervosa was identified in 1997 as a proposed eating disorder best characterized as an obsession with healthy eating with associated restrictive behaviors.¹³ Patients with this disorder are rarely focused on losing weight, and orthorexic eating behaviors have been associated with both SSD and OCD.^12,14 As in Ms. L’s case, patients with orthorexia nervosa demonstrate intrusive obsessions with nutrition, spend excessive amount of time researching nutrition, and fixate on food quality.¹² Throughout Ms. L’s hospitalization, even as her food-related magical thinking symptoms improved, she constantly informed her care team that she had been “eating healthily” even though she was severely cachectic. Patients with SSD and OCD prone to health anxieties are at risk of developing pathologic food beliefs and dangerous eating behaviors. These patients may benefit from psychoeducation regarding nutrition and media literacy, which are components of effective eating disorder programs.¹⁵

[polldaddy:11079399]

Continue to: The authors' observations...

How do we approach the pharmacologic treatment of patients with co-occurring eating, somatic symptom, and anxiety disorders? Olanzapine facilitates recovery in children and adolescents with ARFID by promoting eating and weight gain, and decreasing symptoms of depression and anxiety.¹⁶ Patients with orthorexia nervosa also may benefit from treatment with olanzapine, which has decreased food-related fixations, magical thinking, and delusions regarding food.¹⁷ Further, orthorexic patients with ARFID have also been shown to respond to SSRIs due to those agents’ efficacy for treating intrusive thoughts, obsessions, and preoccupations from OCD and SSD.^18,19 Thus, treating Ms. L’s symptoms with olanzapine and fluoxetine targeted the intersection of several diagnoses on our differential. Olanzapine’s propensity to cause weight gain is favorable in this population, particularly patients such as Ms. L, who do not exhibit body dysmorphia or fear of gaining weight.

OUTCOME Weight gain and fewer fears

Ms. L is prescribed olanzapine 5 mg/d and fluoxetine 20 mg/d. She gains 20.6 pounds in 4 weeks. Importantly, she endorses fewer fears related to foods and expands her palate to include foods she previously considered to be unhealthy, including white bread and farm-raised salmon. Further, she spends less time thinking about food and says she has less anxiety regarding the recurrence of GI symptoms.

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

Study Overview

Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.

Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.

Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.

Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.

Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.

Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.

Commentary

High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.¹ In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.^2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.⁴ Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.³ Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.

In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.

Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.⁵ Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.

Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).⁶ Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.

Applications for Clinical Practice

Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.

—Fred Ko, MD

Study Overview

Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.

Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.

Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.

Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.

Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.

Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.

Commentary

High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.¹ In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.^2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.⁴ Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.³ Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.

In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.

Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.⁵ Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.

Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).⁶ Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.

Applications for Clinical Practice

Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.

—Fred Ko, MD

Study Overview

Objective: This study evaluated whether a clinical-decision-support (CDS) tool that utilizes a real-time algorithm incorporating patient vital sign data can identify hospitalized patients who can forgo overnight vital sign checks and thus reduce delirium incidence.

Design: This was a parallel randomized clinical trial of adult inpatients admitted to the general medical service of a tertiary care academic medical center in the United States. The trial intervention consisted of a CDS notification in the electronic health record (EHR) that informed the physician if a patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model of real-time patient data input. This notification provided the physician an opportunity to discontinue nighttime vital sign checks, dismiss the notification for 1 hour, or dismiss the notification until the next day.

Setting and participants: This clinical trial was conducted at the University of California, San Francisco Medical Center from March 11 to November 24, 2019. Participants included physicians who served on the primary team (eg, attending, resident) of 1699 patients on the general medical service who were outside of the intensive care unit (ICU). The hospital encounters were randomized (allocation ratio of 1:1) to sleep promotion vitals CDS (SPV CDS) intervention or usual care.

Main outcome and measures: The primary outcome was delirium as determined by bedside nurse assessment using the Nursing Delirium Screening Scale (Nu-DESC) recorded once per nursing shift. The Nu-DESC is a standardized delirium screening tool that defines delirium with a score ≥2. Secondary outcomes included sleep opportunity (ie, EHR-based sleep metrics that reflected the maximum time between iatrogenic interruptions, such as nighttime vital sign checks) and patient satisfaction (ie, patient satisfaction measured by standardized Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS] survey). Potential balancing outcomes were assessed to ensure that reduced vital sign checks were not causing harms; these included ICU transfers, rapid response calls, and code blue alarms. All analyses were conducted on the basis of intention-to-treat.

Main results: A total of 3025 inpatient encounters were screened and 1930 encounters were randomized (966 SPV CDS intervention; 964 usual care). The randomized encounters consisted of 1699 patients; demographic factors between the 2 trial arms were similar. Specifically, the intervention arm included 566 men (59%) and mean (SD) age was 53 (15) years. The incidence of delirium was similar between the intervention and usual care arms: 108 (11%) vs 123 (13%) (P = .32). Compared to the usual care arm, the intervention arm had a higher mean (SD) number of sleep opportunity hours per night (4.95 [1.45] vs 4.57 [1.30], P < .001) and fewer nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86], P < .001). The post-discharge HCAHPS survey measuring patient satisfaction was completed by only 5% of patients (53 intervention, 49 usual care), and survey results were similar between the 2 arms (P = .86). In addition, safety outcomes including ICU transfers (49 [5%] vs 47 [5%], P = .92), rapid response calls (68 [7%] vs 55 [6%], P = .27), and code blue alarms (2 [0.2%] vs 9 [0.9%], P = .07) were similar between the study arms.

Conclusion: In this randomized clinical trial, a CDS tool utilizing a real-time prediction algorithm embedded in EHR did not reduce the incidence of delirium in hospitalized patients. However, this SPV CDS intervention helped physicians identify clinically stable patients who can forgo routine nighttime vital sign checks and facilitated greater opportunity for patients to sleep. These findings suggest that augmenting physician judgment using a real-time prediction algorithm can help to improve sleep opportunity without an accompanying increased risk of clinical decompensation during acute care.

Commentary

High-quality sleep is fundamental to health and well-being. Sleep deprivation and disorders are associated with many adverse health outcomes, including increased risks for obesity, diabetes, hypertension, myocardial infarction, and depression.¹ In hospitalized patients who are acutely ill, restorative sleep is critical to facilitating recovery. However, poor sleep is exceedingly common in hospitalized patients and is associated with deleterious outcomes, such as high blood pressure, hyperglycemia, and delirium.^2,3 Moreover, some of these adverse sleep-induced cardiometabolic outcomes, as well as sleep disruption itself, may persist after hospital discharge.⁴ Factors that precipitate interrupted sleep during hospitalization include iatrogenic causes such as frequent vital sign checks, nighttime procedures or early morning blood draws, and environmental factors such as loud ambient noise.³ Thus, a potential intervention to improve sleep quality in the hospital is to reduce nighttime interruptions such as frequent vital sign checks.

In the current study, Najafi and colleagues conducted a randomized trial to evaluate whether a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, can be utilized to identify patients in whom vital sign checks can be safely discontinued at nighttime. The authors found a modest but statistically significant reduction in the number of nighttime vital sign checks in patients who underwent the SPV CDS intervention, and a corresponding higher sleep opportunity per night in those who received the intervention. Importantly, this reduction in nighttime vital sign checks did not cause a higher risk of clinical decompensation as measured by ICU transfers, rapid response calls, or code blue alarms. Thus, the results demonstrated the feasibility of using a real-time, patient data-driven CDS tool to augment physician judgment in managing sleep disruption, an important hospital-associated stressor and a common hazard of hospitalization in older patients.

Delirium is a common clinical problem in hospitalized older patients that is associated with prolonged hospitalization, functional and cognitive decline, institutionalization, death, and increased health care costs.⁵ Despite a potential benefit of SPV CDS intervention in reducing vital sign checks and increasing sleep opportunity, this intervention did not reduce the incidence of delirium in hospitalized patients. This finding is not surprising given that delirium has a multifactorial etiology (eg, metabolic derangements, infections, medication side effects and drug toxicity, hospital environment). A small modification in nighttime vital sign checks and sleep opportunity may have limited impact on optimizing sleep quality and does not address other risk factors for delirium. As such, a multicomponent nonpharmacologic approach that includes sleep enhancement, early mobilization, feeding assistance, fluid repletion, infection prevention, and other interventions should guide delirium prevention in the hospital setting. The SPV CDS intervention may play a role in the delivery of a multifaceted, nonpharmacologic delirium prevention intervention in high-risk individuals.

Sleep disruption is one of the multiple hazards of hospitalization frequently experience by hospitalized older patients. Other hazards, or hospital-associated stressors, include mobility restriction (eg, physical restraints such as urinary catheters and intravenous lines, bed elevation and rails), malnourishment and dehydration (eg, frequent use of no-food-by-mouth order, lack of easy access to hydration), and pain (eg, poor pain control). Extended exposures to these stressors may lead to a maladaptive state called allostatic overload that transiently increases vulnerability to post-hospitalization adverse events, including emergency department use, hospital readmission, or death (ie, post-hospital syndrome).⁶ Thus, the optimization of sleep during hospitalization in vulnerable patients may have benefits that extend beyond delirium prevention. It is perceivable that a CDS tool embedded in EHR, powered by a real-time prediction algorithm of patient data, may be applied to reduce some of these hazards of hospitalization in addition to improving sleep opportunity.

Applications for Clinical Practice

Findings from the current study indicate that a CDS tool embedded in EHR that utilizes a real-time prediction algorithm of patient data may help to safely improve sleep opportunity in hospitalized patients. The participants in the current study were relatively young (53 [15] years). Given that age is a risk factor for delirium, the effects of this intervention on delirium prevention in the most susceptible population (ie, those over the age of 65) remain unknown and further investigation is warranted. Additional studies are needed to determine whether this approach yields similar results in geriatric patients and improves clinical outcomes.

—Fred Ko, MD

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

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

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

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

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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