Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3Δ25bpIntronic Deletion in South Asian Descendants.

Importance: The genetic variant MYBPC3Δ25bp occurs in 4% of South Asian descendants, with an estimated 100 million carriers worldwide. MYBPC3 Δ25bp has been linked to cardiomyopathy and heart failure. However, the high prevalence of MYBPC3Δ25bp suggests that other stressors act in concert with MYBPC3Δ25bp. Objective: To determine whether there are additional genetic factors that contribute to the cardiomyopathic expression of MYBPC3Δ25bp. Design, Setting, andParticipants: South Asian individuals living in the United States were screened for MYBPC3Δ25bp, and a subgroup was clinically evaluated using electrocardiograms and echocardiograms at Loyola University, Chicago, Illinois, between January 2015 and July 2016. Main Outcomes and Measures: Next-generation sequencing of 174 cardiovascular disease genes was applied to identify additional modifying gene mutations and correlate genotype-phenotype parameters. Cardiomyocytes derived from human-induced pluripotent stem cells were established and examined to assess the role of MYBPC3Δ25bp. Results: In this genotype-phenotype study, individuals of South Asian descent living in the United States from both sexes (36.23% female) with a mean population age of 48.92 years (range, 18-84 years) were recruited. Genetic screening of 2401 US South Asian individuals found an MYBPC3Δ25bpcarrier frequency of 6%. A higher frequency of missense TTN variation was found in MYBPC3Δ25bp carriers compared with noncarriers, identifying distinct genetic backgrounds within the MYBPC3Δ25bp carrier group. Strikingly, 9.6% of MYBPC3Δ25bp carriers also had a novel MYBPC3 variant, D389V. Family studies documented D389V was in tandem on the same allele as MYBPC3Δ25bp, and D389V was only seen in the presence of MYBPC3Δ25bp. In contrast to MYBPC3Δ25bp, MYBPC3Δ25bp/D389V was associated with hyperdynamic left ventricular performance (mean [SEM] left ventricular ejection fraction, 66.7 [0.7%]; left ventricular fractional shortening, 36.6 [0.6%]; P < .03) and stem cell-derived cardiomyocytes exhibited cellular hypertrophy with abnormal Ca2+ transients. Conclusions and Relevance: MYBPC3Δ25bp/D389V is associated with hyperdynamic features, which are an early finding in hypertrophic cardiomyopathy and thought to reflect an unfavorable energetic state. These findings support that a subset of MYBPC3Δ25bp carriers, those with D389V, account for the increased risk attributed to MYBPC3Δ25bp.

Effect of depression treatment on depressive symptoms in older adulthood: the moderating role of pain.

OBJECTIVES: To investigate whether pain severity and interference with normal work activities moderate the effects of depression treatment on changes in depressive symptoms over time in older adults in primary care. DESIGN: Patient-randomized, clinical trial. SETTING: Multisite: three clinics located in Veterans Affairs Medical Centers. PARTICIPANTS: Adults aged 60 and older (n=524) who screened positive for depression and participated in the Primary Care Research in Substance Abuse and Mental Health for the Elderly Study. INTERVENTION: Integrated care versus enhanced specialty referral care. MEASUREMENTS: Pain severity, the degree to which pain interferes with work inside and outside of the home, and depressive symptoms were examined at baseline and 3, 6, and 12 months. RESULTS: Intention-to-treat analyses revealed that both treatment groups showed reduced depressive symptoms over time, although self-reported pain moderated reductions in depressive symptoms. At higher levels of pain severity and interference with work activities, improvements in depressive symptoms were blunted. Furthermore, pain interference appeared to have a greater effect on depressive symptoms than did pain severity; in individuals with major depression, pain interference fully accounted for the moderating effects of pain severity on changes in depressive symptoms over time. CONCLUSION: Pain and its interference with functioning interfere with recovery from depression. Findings highlight the importance of addressing multiple domains of functioning (e.g., physical and social disability) and the degree to which pain and other forms of physical comorbidity may hinder or minimize treatment-related improvements in depressive symptoms.

Alcohol consumption among older adults in primary care.

BACKGROUND: Alcohol misuse is a growing public health concern for older adults, particularly among primary care patients. OBJECTIVES: To determine alcohol consumption patterns and the characteristics associated with at-risk drinking in a large sample of elderly primary care patients. DESIGN: Cross-sectional analysis of multisite screening data from 6 VA Medical Centers, 2 hospital-based health care networks, and 3 Community Health Centers. PARTICIPANTS: Patients, 43,606, aged 65 to 103 years, with scheduled primary care appointments were approached for screening; 27,714 (63.6%) consented to be screened. The final sample of persons with completed screens comprised 24,863 patients. MEASUREMENTS: Quantity and frequency of alcohol use, demographics, social support measures, and measures of depression/anxiety. RESULTS: Of the 24,863 older adults screened, 70.0% reported no consumption of alcohol in the past year, 21.5% were moderate drinkers (1-7 drinks/week), 4.1% were at-risk drinkers (8-14 drinks/week), and 4.5% were heavy (>14 drinks/week) or binge drinkers. Heavy drinking showed significant positive association with depressive/anxiety symptoms [Odds ratio (OR) (95% CI): 1.79 (1.30, 2.45)] and less social support [OR (95% CI): 2.01 (1.14, 2.56)]. Heavy drinking combined with binging was similarly positively associated with depressive/anxiety symptoms [OR (95%): 1.70 (1.33, 2.17)] and perceived poor health [OR (95% CI): 1.27 (1.03, 1.57)], while at-risk drinking was not associated with any of these variables. CONCLUSIONS: The majority of participants were nondrinkers; among alcohol users, at-risk drinkers did not differ significantly from moderate drinkers in their characteristics or for the 3 health parameters evaluated. In contrast, heavy drinking was associated with depression and anxiety and less social support, and heavy drinking combined with binge drinking was associated with depressive/anxiety symptoms and perceived poor health.

Exposure to trauma and posttraumatic stress disorder symptoms in older veterans attending primary care: comorbid conditions and self-rated health status.

OBJECTIVES: Assess the prevalence of posttraumatic stress disorder (PTSD) symptomatology and its association with health characteristics in a geriatric primary care population. DESIGN: Cross-sectional screening assessments during a multisite trial for the treatment of depression, anxiety, and at-risk drinking. SETTING: Department of Veterans Affairs (VA)-based primary care clinics across the United States. PARTICIPANTS: Seventeen thousand two hundred five veterans aged 65 and older. MEASUREMENTS: Sociodemographic information, the General Health Questionnaire (GHQ-12), questions about death wishes and suicidal ideation, quantity and frequency of alcohol use, smoking, exposure to traumatic events, and PTSD symptom clusters. RESULTS: Twelve percent (2,041/17,205) of participants screened endorsed PTSD symptoms. Veterans with PTSD symptoms from some (partial PTSD) or each (PTSD all clusters) of the symptom clusters were significantly more likely to report poor general health, currently smoke, be divorced, report little or no social support, and have a higher prevalence of mental distress, death wishes, and suicidal ideation than those with no trauma history or those with trauma but no symptoms. Group differences were most pronounced for mental distress and least for at-risk drinking. Presence of PTSD all clusters was associated with poorer outcomes on all of the above-mentioned health characteristics than partial PTSD. CONCLUSION: PTSD symptoms are common in a substantial minority of older veterans in primary care, and careful inquiry about these symptoms is important for comprehensive assessment in geriatric populations.

Satisfaction with mental health services in older primary care patients.

OBJECTIVE: This study examines whether older adult primary care patients are satisfied with two intervention models designed to ameliorate their behavioral health problems. METHODS: A total of 1,052 primary care patients aged 65 and older with depression, anxiety, or at-risk drinking were randomly assigned to and participated in either integrated care (IC) or enhanced specialty referral (ESR) model and completed the Client Satisfaction Questionnaire (CSQ) administered at three-month follow-up assessment. RESULTS: Older adult patients' satisfaction with IC (mean: 3.4, standard deviation [SD]: 0.60) was significantly higher than that with ESR (mean: 3.2, SD: 0.78), but the absolute difference was modest. Regression results showed that patients who used the IC model, attended the treatment service twice or more, or showed clinical improvement were more likely to express greater satisfaction. Stigma toward mental illness was negatively associated with satisfaction with mental health services. CONCLUSIONS: Older adults are more likely to have greater satisfaction with mental health services integrated in primary care settings than through enhanced referrals to specialty mental health and substance abuse clinics.

Suicidal and death ideation in older primary care patients with depression, anxiety, and at-risk alcohol use.

The authors identified correlates of active suicidal ideation and passive death ideation in older primary care patients with depression, anxiety, and at-risk alcohol use. Participants included 2,240 older primary care patients (age 65+), who were identified in three mutually exclusive groups on the basis of responses to the Paykel suicide questions: No Ideation, Death Ideation, and Suicidal Ideation. Chi-square, ANOVA, and polytomous logistic regression analyses were used to identify characteristics associated with suicidal ideation. The highest amount of suicidal ideation was associated with co-occurring major depression and anxiety disorder (18%), and the lowest proportion occurred in at-risk alcohol use (3%). Asians have the highest (57%) and African Americans have the lowest (27%) proportion of suicidal or death ideation. Fewer social supports and more severe symptoms were associated with greater overall ideation. Death ideation was associated with the greatest medical comorbidity and highest service utilization. Contrary to previous reports, authors failed to find that active suicidal ideation was associated with increased contacts with healthcare providers. Accordingly, targeted assessment and preventive services should be emphasized for geriatric outpatients with co-occurring depression and anxiety, social isolation, younger age, and Asian or Caucasian race.