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BACKGROUND: Healthy lifestyle is associated with reduced all-cause mortality, but it is not known whether this association persists for individuals with high medication burden. We examined the association between healthy lifestyle behaviors and all-cause mortality across different degrees of polypharmacy. METHODS: This was a secondary analysis of 20,417 adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study. The primary exposure was healthy lifestyle (adherence to Mediterranean diet, physical activity, smoking abstinence, sedentary behavior avoidance, and composite healthy behavior score [HBS]). The primary outcome was all-cause mortality. Strata of medication burden were based on the number of medications taken (no polypharmacy:0–4, polypharmacy:5–9, hyperpolypharmacy:≥10). We used Cox proportional hazards regression models to examine the association between healthy lifestyle behaviors and mortality within each medication burden stratum; and examined for interactions with age. RESULTS: The healthiest category of each lifestyle behavior, except sedentary behavior avoidance among the hyperpolypharmacy group, was associated with lower all-cause mortality (hazard ratio [HR], 95% confidence interval [95%CI]) regardless of medication burden: Mediterranean diet (no polypharmacy: HR 0.77, polypharmacy: HR 0.78, hyperpolypharmacy: HR 0.85, physical activity (no polypharmacy: HR 0.87, polypharmacy: HR 0.82, hyperpolypharmacy: HR 0.79, smoking abstinence (no polypharmacy: HR 0.40, polypharmacy: HR 0.45, hyperpolypharmacy: HR 0.52, and sedentary behavior avoidance (no polypharmacy: HR 0.88, polypharmacy: HR 0.86, hyperpolypharmacy: HR 0.95. Higher HBS was inversely associated with all-cause mortality within each medication burden stratum (no polypharmacy: HR 0.52, polypharmacy: HR 0.55, hyperpolypharmacy: HR 0.69. Although there was an interaction with age among those with no polypharmacy and those with polypharmacy, point estimates for HBS followed a graded pattern whereby higher HBS was incrementally associated with improved mortality across all age strata. CONCLUSION: Greater adherence to a healthy lifestyle was associated with lower all-cause mortality irrespective of medication burden and age.

Objective To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine. Methods Two hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures. Results Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18–59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures. Conclusion Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not.

Objective This study tested the hypotheses that, in older adults with remitted major depression, a history of psychotic features and poorer neuropsychological performance would be independently associated with poorer everyday functioning, but that neuropsychological performance would explain more of the variance in functioning than history of psychotic features. Methods This cross-sectional study included 73 patients aged 50 years or older with remitted psychotic major depression or nonpsychotic major depression. The dependent variables were subjective and objective measures of function. The independent variables were history of psychotic features during one or more major depressive episodes in the previous 10 years and neuropsychological performance. Linear regression models examined the association of independent variables with function, controlling for pertinent covariates. Effect sizes were calculated for the magnitude of difference in function between the patient participants and an age- and gender-matched nonpsychiatric group, and distribution of functioning scores were compared between groups. Results In separate models, history of psychotic features and poorer processing speed, executive function, and verbal learning were independently associated with poorer participant-reported functioning and performance-based functioning. However, the association of psychotic features with functioning was no longer statistically significant when tested in the same models as neuropsychological measures. Effect sizes of the difference in functioning between patients and the nonpsychiatric group were significantly larger for the remitted psychotic than the remitted nonpsychotic depression group; functioning scores were more heterogeneous in the remitted psychotic depression group. Conclusion Patients with remitted psychotic depression exhibit greater, and clinically important, impairment in everyday functioning than those with remitted nonpsychotic depression. Neuropsychological impairment appears to contribute to this relationship.

Objective Poststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults with PSD and to evaluate their relationship to cognitive functioning. Design Cross-sectional factor and correlational analyses of patients with poststroke depression. Setting Patients were recruited from the community and from acute inpatient stroke rehabilitation hospitals. Participants Participants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Asberg Depression Scale; MADRS). Intervention None. Measurements MADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language. Results There were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment. Conclusion PSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment.

OBJECTIVE: The study examines the relationship of negative emotions with: 1) non-emotional symptoms (e.g., vegetative and physical symptoms) and 2) the course of depression in suicidal older adults with Major Depressive Disorder (MDD) and cognitive impairment treated with psychotherapy. DESIGN: The authors identified a subgroup of participants (N = 26) who expressed suicidal ideation at Baseline or Week 12 from a randomized controlled trial (RCT) of two psychosocial interventions, Problem Adaptation Therapy (PATH) and Supportive Therapy for Cognitively Impaired. The authors assessed negative emotions, non-emotional symptoms of depression, depression severity, and suicidal ideation at entry, week 4, week 8, and week 12. PARTICIPANTS: Participants were 65 years and older and had a diagnosis of unipolar depression, varying degrees of cognitive impairment (up to moderate dementia) and suicidal ideation. SETTING: The study was conducted in the Outpatient Department of New York Presbyterian/Weill Cornell Medicine in Westchester, NY. MEASUREMENTS: Negative emotions and non-emotional items were identified with the 24-item Hamilton Depression Rating Scale (Ham-D). RESULTS: Among participants with suicidal ideation, the reduction in negative emotions from baseline to week 4, week 4 to week 8, and week 8 to week 12 was significantly associated with the reduction in non-emotional symptoms of depression at weeks 4, 8, and 12 (F((1, 35)) = 6.20, p = 0.02) and with the reduction in overall depression severity at weeks 4, 8, and 12 (F((1, 35)) = 26.63, p

Background: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). Methods: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association’s COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. Results: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03–1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10–1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65–1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84–1.33]). Conclusions: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

Background Some patients with major depression continue to demonstrate deficits in health-related quality of life (HRQL) following remission. No data exist, however, regarding HRQL in remitted psychotic depression. In this study, we aimed to characterize HRQL in patients with psychotic depression receiving controlled pharmacotherapy. Methods This is a secondary analysis of a randomized controlled trial studying continuation pharmacotherapy of psychotic depression. We compared participants’ HRQL (measured using the SF-36) between baseline and remission and to population norms. We also compared SF-36 scores stratified by age and gender and examined the correlation between SF-36 scores and medical burden, depression score and neuropsychological performance in remission. Results SF-36 scores were significantly lower than population norms at baseline, but improved following remission to the level of population norms. Neither SF-36 scores nor magnitude of SF-36 improvement differed substantially between genders or between younger and older participants. In remission, depression scores were correlated with most SF-36 scales and medical burden was correlated with SF-36 scales measuring physical symptoms. Neuropsychological measures were generally not correlated with SF-36 scores. Limitations This study was a secondary analysis not powered specifically to measure HRQL as an outcome variable and the SF-36 was the only HRQL measure used. Conclusions Participants with remitted psychotic depression demonstrated levels of HRQL comparable to population norms, despite marked impairment in HRQL when acutely ill. This finding suggests that, when treated in a rigorous manner, many patients with this severe illness improve significantly from a clinical and HRQL perspective.

Objective: The authors assessed the impact of a shared decision-making (SDM) intervention among elderly depressed minority primary care patients not currently receiving treatment. Methods: A total of 202 English and Spanish-speaking primary care participants aged 65 and older who scored positive on the Patient Health Questionnaire-9 (≥10) were randomized at the physician level to receive a brief SDM intervention or usual care (UC). Primary analyses focused on patient adherence to either psychotherapy or antidepressant medication, and reduction in depression severity (Hamilton Depression Rating Scale) over 12 weeks. Results: Patients randomized to physicians in the SDM condition were significantly more likely than patients of physicians randomized to UC to receive a mental health evaluation or initiate some form of treatment (39% versus 21%), and to adhere to psychotherapy visits over 12 weeks. There were no differences between groups in adherence to antidepressant medication or in reduction of depressive symptoms. Conclusion: Among untreated elderly depressed minority patients from an inner-city municipal hospital, a brief SDM intervention was associated with greater initiation and adherence to psychotherapy. However, low treatment adherence rates across both groups and the intervention's lack of impact on clinical outcomes highlight the need to provide focused and accessible mental health services to patients choosing active treatments.

Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania.The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 μg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS).Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively).Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks.

Background While an expanding armamentarium of pharmacologic therapies has contributed to improved outcomes among adults with heart failure (HF) over the past two decades, this has also been accompanied by an increase in the number of medications taken by adults with HF. The use of at least 10 medications, defined as hyperpolypharmacy, is particularly notable given its association with adverse outcomes. We aimed to assess the prevalence and identify determinants of hyperpolypharmacy among adults with HF. Methods We studied adults aged ≥50 years with self-reported HF from the National Health And Nutrition Examination Survey (NHANES) in 2003–2014. We calculated weighted means and percentages to describe patient characteristics. We conducted a multivariable Poisson regression analysis to identify factors independently associated with hyperpolypharmacy; we adjusted for survey sampling, socio-demographics, comorbidity, geriatric conditions, and health care utilization. We examined 947 participants, representing 4.6 million adults with HF. Results The prevalence of hyperpolypharmacy was 26%. In a multivariable regression analysis, comorbidity count, ≥10 ambulatory contacts, and ≥ 3 hospitalizations were independently associated with hyperpolypharmacy. Interestingly, functional impairment and cognitive impairment were not independently associated with hyperpolypharmacy; while low annual household income and low educational status were each associated with an almost 2-fold increase in hyperpolypharmacy. Conclusion Hyperpolypharmacy is a common condition among adults with HF. We additionally found that low household income and low educational status are independently associated with hyperpolypharmacy, suggesting that non-medical factors may be contributing to this potentially harmful condition.

Magnetic resonance imaging/ultrasound-guided fusion biopsy (FBx) is more accurate at detecting clinically significant prostate cancer than conventional transrectal ultrasound-guided systematic biopsy. However, learning curves for attaining accuracy may limit the generalizability of published outcomes.To delineate and quantify the learning curve for FBx by assessing the targeted biopsy accuracy and pathological quality of systematic biopsy over time.We carried out a retrospective analysis of 173 consecutive men who underwent Artemis FBx with computer-template systematic sampling between July 2015 and May 2017.The accuracy of targeted biopsy was determined by calculating the distance between planned and actual core trajectories stored on Artemis. Systematic sampling proficiency was assessed via pathological analysis of fibromuscular tissue in all cores and then comparing pathology elements from individual cores from men in the first and last tertiles. Polynomial linear regression models, change-point analysis, and piecewise linear regression were used to quantify the learning curve.A significant improvement in targeted biopsy accuracy occurred up to 98 cases (p0.01). There was a significant decrease in fibromuscular tissue in the systematic biopsy cores up to 84 cases (p0.01) and an improvement in pathological quality when comparing systematic cores from the first and third tertiles. Use of a different fusion platform may limit the generalizability of our results.There is a significant learning curve for targeted and systemic biopsy using the Artemis platform. Improvements in accuracy of targeted biopsy and better sampling for systematic biopsy can be achieved with greater experience.We define the learning curve for magnetic resonance imaging/ultrasound-guided fusion biopsy (FBx) using targeted biopsy accuracy and systematic core sampling quality as measures. Our findings underscore the importance of overcoming learning curves inherent to FBx to minimize patient discomfort and biopsy risk and improve the quality of care for accurate risk stratification, active surveillance, and treatment selection.

Background Cognitive impairment (CI) is estimated to be present in 25%–80% of heart failure (HF) patients, but its prevalence at diagnosis is unclear. To improve our understanding of cognition in HF, we determined the prevalence of CI among adults with incident HF in the REGARDS study. Methods and Results REGARDS is a longitudinal cohort study of adults ≥45 years of age recruited in the years 2003–2007. Incident HF was expert adjudicated. Cognitive function was assessed with the Six-Item Screener. The prevalence of CI among those with incident HF was compared with the prevalence of CI among an age-, sex-, and race-matched cohort without HF. The 436 participants with incident HF had a mean age of 70.3 years (SD 8.9), 47% were female, and 39% were black. Old age, black race, female sex, less education, and anticoagulation use were associated with CI. The prevalence of CI among participants with incident HF (14.9% [95% CI 11.7%–18.6%]) was similar to the non-HF matched cohort (13.4% [11.6%–15.4%]; P Conclusions A total of 14.9% of the adults with incident HF had CI, suggesting that the majority of cognitive decline occurs after HF diagnosis. Increased awareness of CI among newly diagnosed patients and ways to mitigate it in the context of HF management are warranted.

Objective Primary care is the de facto mental health system in the United States where physicians treat large numbers of depressed older adults with antidepressant medication. This study aimed to examine whether antidepressant dosage adequacy and patient adherence are associated with depression response among middle-aged and older adults prescribed with antidepressants by their primary care provider. Design A secondary analysis was conducted on a sample drawn from a randomized controlled trial comparing Treatment as Usual to Treatment Initiation Program, an adherence intervention. Treatment Initiation Program improved adherence but not depression compared to Treatment as Usual (Sirey et al., 2017). For this analysis, we examined dosing adequacy and adherence at 6 and 12 weeks as predictors of depression response in both groups at 12 and 24 weeks. Setting Primary care practices. Participants One hundred eighty-seven older adults with depression prescribed an antidepressant for depression by their primary care provider. Measurements Depression response was defined as 50% reduction on the Hamilton Rating Scale for Depression. Adherence was defined as taking 80% of doses at follow-up interviews (6 and 12 weeks). Patient-reported dosage and duration of antidepressant therapy was collected using the Composite Antidepressant Score (adequacy score of >3) at follow-up. Results Greater adherence, but not receipt of adequate dosage, was associated with higher likelihood of treatment response at both 12 (Odds ratio (OR) = 2.63; 95% Confidence Interval (CI), 1.19–5.84) and 24 weeks (OR = 3.09; 95% CI, 1.46–6.55). Conclusion As physicians prescribe antidepressants to the diverse group of adults seen in primary care, special attention to patients’ views and approach to adherence may improve depression outcomes.

Objective We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). Methods Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. Results The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. Conclusion Continuation of acute treatment was associated with stability of remission.

Graphical abstract, From early March through mid-May 2020, the COVID-19 pandemic overwhelmed hospitals in New York City. In anticipation of ventilator shortages and limited ICU bed capacity, hospital operations prioritized the development of prognostic tools to predict clinical deterioration. However, early experience from frontline physicians observed that some patients developed unanticipated deterioration after having relatively stable periods, attesting to the uncertainty of clinical trajectories among hospitalized patients with COVID-19. Prediction tools that incorporate clinical variables at one time-point, usually on hospital presentation, are suboptimal for patients with dynamic changes and evolving clinical trajectories. Therefore, our study team developed a machine-learning algorithm to predict clinical deterioration among hospitalized COVID-19 patients by extracting clinically meaningful features from complex longitudinal laboratory and vital sign values during the early period of hospitalization with an emphasis on informative missing-ness. To incorporate the evolution of the disease and clinical practice over the course of the pandemic, we utilized a time-dependent cross-validation strategy for model development. Finally, we validated our prediction model on an external validation cohort of COVID-19 patients served in a demographically distinct population from the training cohort. The main finding of our study is the identification of risk profiles of early, late and no clinical deterioration during the course of hospitalization. While risk prediction models that include simple predictors at ED presentation and clinical judgement are able to identify any deterioration vs. no deterioration, our methodology is able to isolate a particular risk group that remain stable initially but deteriorate at a later stage of the course of hospitalization. We demonstrate the superior predictive performance with the utilization of laboratory and vital sign data during the early period of hospitalization compared to the utilization of data at presentation alone. Our results will allow efficient hospital resource allocation and will motivate research in understanding the late deterioration risk group.

OBJECTIVE To examine the association between baseline suicidality and outcome of major depression in a randomized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality, randomized treatment assignment, and depression outcome. METHODS This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo (the Study of the Pharmacotherapy of Psychotic Depression [STOP-PD], which ran from 2002 to 2007). The independent variable was baseline suicidality, defined by 4 groups (suicide attempt in the current episode, active suicidal ideation, passive suicidal ideation, and no suicidality). The outcome variables were change in 16-item Hamilton Depression Rating Scale (HDRS₁₆) total score (excluding the suicide item) over time and remission of psychotic depression over time. RESULTS Suicidality groups did not significantly differ on baseline HDRS₁₆ total score. Baseline suicidality group was significantly associated with change in HDRS₁₆ score over time in the sample as a whole (F₃,₁₃₉₄ = 8.17; P < .0001), but was not significantly associated with probability of remission over time. Among participants assigned to olanzapine and placebo, persons with no suicidality had a significantly greater reduction in HDRS₁₆ total score compared to those with passive suicidal ideation (7.5-point difference in change scores between the 2 groups; 95% CI, 4.3-10.7 t₁₃₉₄ = 4.61, P < .0001), active suicidal ideation (4.4 points; 95% CI, 1.4-7.4; t₁₃₉₄ = 2.85, P = .0176), or suicide attempts (6.1 points; 95% CI, 2.8-9.4; t₁₃₉₄ = 3.66, P = .0015). The 12-week change from baseline in HDRS₁₆ score for patients with no suicidality was not significantly different between the 2 treatment arms. However, the 12-week HDRS₁₆ improvement was significantly greater in the olanzapine plus sertraline arm, compared with the olanzapine plus placebo arm, for patients with suicide attempts (8.7-point difference in change scores between the 2 groups; 95% CI, 5.1-12.4; t₁₃₉₄ = 4.75, P < .0001), active suicidal ideation (8.1 points; 95% CI, 4.5-11.7; t₁₃₉₄ = 4.38, P < .0001), or passive suicidal ideation (5.7 points; 95% CI, 2.2-9.2; t₁₃₉₄ = 3.23, P = .0012), respectively. CONCLUSIONS Baseline suicidality predicted worse acute treatment outcome of psychotic depression. However, participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00056472​.

ObjectiveResearch on the impact of natural disasters on the mental health of older adults finds both vulnerabilities and resilience. We report on the rates of clinically significant depression among older adults (aged ≥60 years) living in areas affected by Hurricane Sandy in 2012 and the factors associated with mental health need.MethodsThe Sandy Mobilization, Assessment, Referral and Treatment for Mental Health (SMART-MH) program integrates community outreach and needs assessments to identify older adults with mental health and aging service needs. Older adults with significant anxiety or depressive symptoms were offered short-term psychotherapy. Social service referrals were made directly to community agencies. All SMART-MH activities were offered in Spanish, Russian, Mandarin/Cantonese, and English.ResultsAcross the full sample, 14% of participants screened positive for depression. Hurricane Sandy stressors predicted increased odds of depression, including storm injury, post-storm crime, and the total count of stressors. Outcomes varied significantly by age group, such that all Sandy-related variables remained significant for younger-old adults (aged 60–74 years), whereas only the loss of access to medical care was significant for older-old adults (aged ≥75 years).ConclusionsStorm-affected communities show higher rates of depressive symptoms than seen in the general population, with storm stressors affecting mental health needs differentially by age group. (Disaster Med Public Health Preparedness. 2017;11:97–109)

Objective Personalized Intervention for Depressed Patients with COPD (PID-C), a treatment mobilizing patients to participate in their care, was found more effective than usual care. To further improve its efficacy, we developed a Problem Solving-Adherence (PSA) intervention integrating problem solving into adherence enhancement procedures. We tested the hypothesis that PSA is more effective than PID-C in reducing depressive symptoms. Exploratory analyses sought to identify patients with distinct depressive symptom trajectories and compare their clinical profiles. Design Randomized controlled trial. Setting Acute inpatient rehabilitation and community. Participants A total of 101 diagnosed with chronic obstructive pulmonary disease (COPD) and major depression after screening 633 consecutive admissions for acute inpatient rehabilitation. Intervention Fourteen sessions of PID-C versus PSA over 26 weeks. Measurements 24-item Hamilton Depression Rating Scale. Results PSA was not more efficacious than PID-C in reducing depressive symptoms. Exploratory latent class growth modeling identified two distinct depressive symptoms trajectories. Unlike patients with unfavorable course (28%) who remained symptomatic, patients with favorable course (72%) had a decline of symptoms during the hospitalization followed by a milder decline after discharge. Patients with unfavorable course were younger and had greater scores in disability, anxiety, neuroticism, and dyspnea related limitation in activities and lower self-efficacy scores. Conclusions Both interventions led to sustained improvement depressive symptoms. PID-C matches the skills of clinicians employed by community rehabilitation programs and can be integrated in the care of depressed COPD patients. Patients with severe disability, anxiety, neuroticism, and low self-efficacy are at risk for poor outcomes and in need of close follow-up and targeted interventions.

COPD is a major cause of all-cause mortality. We examined predictors of 1-year mortality in patients with severe COPD and major depression after inpatient treatment in a rehabilitation hospital.We screened 898 consecutively admitted patients. Of these, 138 patients received the diagnoses of COPD according to American Thoracic Society Guidelines and major depression by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and signed consent; 67 were randomized to a treatment adherence enhancement intervention and 71 to usual care. We assessed history of falls, dyspnea-related disability, severity of depression, medical burden, and cognitive functioning. Following discharge from inpatient rehabilitation, participants were prospectively followed, and mortality was ascertained over 52 weeks from hospital notes and reports of primary care physicians and relatives.One-year, all-cause mortality was 22% (31 of 138). Multivariate Cox regression analysis showed that history of falls in the 6 months preceding hospital admission was the strongest predictor of mortality (OR, 3.05; 95% CI, 1.40-6.66; P.005). Dyspnea during activities (Pulmonary Functional Status and Dyspnea Questionnaire-Modified domain) was also associated with mortality (OR, 1.05; 95% CI, 1.02-1.08; P.002). Depression severity, medical burden, and cognitive impairment were not predictors of mortality.Recent falls and dyspnea during activities identify subgroups of depressed patients with COPD at increased risk for all-cause mortality. These subgroups are in need of clinical attention and follow-up and can serve as targets for prevention research aiming to inform clinical strategies and public health planning.

Objectives: This study used the Evans model of public health determinants to identify factors associated with nutritional risk in older adults. Design: The Evans model domains (physical and mental well-being, social/environmental statuses, individual choice, and economic security) were measured in a sample of homebound older adults. Regularized logistic regression analysis with LASSO penalty function was used to determine the strongest domain of the Evans model. Using traditional logistic regression, individual variables across all domains were compared to identify the significant predictors. Setting: Older adults receiving home meal services were referred to the study by community program staff. Participants: Participants included 164 homebound older adults (age > 60) who endorsed at least one gateway symptom of depression. Measurements: Nutritional risk was determined using the Mini Nutritional Assessment. Domains of the Evans model were measured using the MAI Medical Condition Checklist, items from the IADL scale, the Structured Clinical Interview for DSM-IV Axis I Disorders, the Duke Social Support Index, living arrangements, marital status, the Alcohol Use Disorders Identification Test, items from the SCID Screening Module, and a self-report of perceived financial security. Results: Poor mental well-being, defined by a diagnosis of major depressive disorder, was identified as the strongest Evans model domain in the prediction of nutritional risk. When each variable was independently evaluated across domains, instrumental support (Wald’s Z=-2.24, p=0.03) and a history of drug use (Wald’s Z=-2.40, p=0.02) were significant predictors. Conclusions: The Evans model is a useful conceptual framework for understanding nutritional health, with the mental domain found to be the strongest domain predictor of nutritional risk. Among individual variables across domains, having someone to help with shopping and food preparation and a history of drug use were associated with lower nutritional risk. These analyses highlight potential targets of intervention for nutritional risk among older adults.

OBJECTIVES: We sought to identify clinical and MRI characteristics in men with PI-RADS category 3 index lesions that predict clinically significant prostate cancer (PCa) on MRI targeted biopsy. MATERIALS AND METHODS: Multi-center study of prospectively collected data for biopsy-naive men (n=247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant PCa (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant PCa. The probability distributions of clinically significant PCa based on different levels of predictors of multivariable models were plotted in a heatmap. RESULTS: Men with clinically significant PCa had smaller prostate volume (39.20 vs 55.10 mL, p0.15 ng/ml2 (OR 3.51, 95%CI 1.61–7.68) were independently associated with significant PCa. CONCLUSION: Higher PSA density, lower prostate volume and ADC values are associated with clinically significant PCa in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant PCa based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.

Objective We present a method for comparing association networks in a matched case-control design, which provides a high-level comparison of co-occurrence patterns of features after adjusting for confounding factors. We demonstrate this approach by examining the differential distribution of chronic medical conditions in patients with major depressive disorder (MDD) compared to the distribution of these conditions in their matched controls. Materials and methods Newly diagnosed MDD patients were matched to controls based on their demographic characteristics, socioeconomic status, place of residence, and healthcare service utilization in the Korean National Health Insurance Service’s National Sample Cohort. Differences in the networks of chronic medical conditions in newly diagnosed MDD cases treated with antidepressants, and their matched controls, were prioritized with a permutation test accounting for the false discovery rate. Sensitivity analyses for the associations between prioritized pairs of chronic medical conditions and new MDD diagnosis were performed with regression modeling. Results By comparing the association networks of chronic medical conditions in newly diagnosed depression patients and their matched controls, five pairs of such conditions were prioritized among 105 possible pairs after controlling the false discovery rate at 5%. In sensitivity analyses using regression modeling, four out of the five prioritized pairs were statistically significant for the interaction terms. Conclusion Association networks in a matched case-control design can provide a high-level comparison of comorbid features after adjusting for confounding factors, thereby supplementing traditional clinical study approaches. We demonstrate the differential co-occurrence pattern of chronic medical conditions in patients with MDD and prioritize the chronic conditions that have statistically significant interactions in regression models for depression.

BACKGROUND: Given the inherent risks of taking a high number of medications, balancing the potential benefits and risks of prescribing a high number of medications is important to optimizing outcomes of adults with heart failure (HF). It is not known whether the number of medications taken by adults with HF who have an impairment in their activities of daily living (ADL)—a subpopulation in whom the risks of a high medication burden may outweigh the benefits—differs from those without such an impairment. METHODS: We examined adults aged ≥50 years with self-reported HF from the National Health and Nutrition Examination Survey (2003–2014), a cross-sectional survey that produces national estimates of adults in the United States. We assessed ADL-impairment and medication count based on self-report. ADL-impairment was defined as having difficulty with or being unable to dress, feed, or get in and out of bed. To determine the independent association between ADL-impairment and medication count, we performed sequential Poisson multivariable regression analyses. All analyses were cross-sectional in nature, and accounted for NHANES’ complex survey design. RESULTS: We studied 947 participants, which represented 4.6 million adults with HF in the United States. The mean age was 70 years. The mean medication count was 7.2 and 74% took ≥5 medications (i.e., polypharmacy). In a multivariable model, ADL-impairment was not independently associated with medication count. These findings were similar for those with ≥3 hospitalizations in the prior year, declining health status, and cognitive impairment. CONCLUSION: After adjusting for confounders including comorbidity, we found that adults with HF and ADL-impairment take as many medications as those without ADL-impairment. This suggests that providers may not sufficiently consider functional impairment when prescribing medications to adults with HF, and thus may unnecessarily expose individuals to an increased risk for adverse outcomes.

The goal of this pilot program was to test the feasibility of mental health screening among elder abuse victims and of offering those victims a brief psychotherapy for depression and anxiety. Elder abuse victims who sought assistance from a large, urban elder abuse service were screened for depression and anxiety using standardized measures. Clients with clinically significant depression (PHQ-9) or anxiety (GAD-7) were randomized to receive one of three different interventions concurrent with abuse resolution services. Staff were able to screen 315 individuals, with 34% of clients scoring positive for depression or anxiety. Of those with mental health needs, only 15% refused all services. The mental health intervention (PROTECT) was successfully implemented in two different formats with collaboration between staff workers. These findings support both the need for mental health care among elder abuse victims and the feasibility of integrating mental health screening and treatment into routine elder abuse practice.

The regulation of medical devices has attracted controversy recently because of problems related to metal-on-metal hip implants. There is growing evidence that metal-on-metal implants fail early and cause local and systemic complications. However, the failure associated with metal-on-metal head size is not consistently documented and needs to be communicated to patients and surgeons. The purpose of this study is to compare implant survival of metal on metal with that of metal on highly cross-linked polyethylene.Using a distributed health data network, primary total hip arthroplasties were identified from six national and regional total joint arthroplasty registries (2001 to 2010). Inclusion criteria were patient age of forty-five to sixty-four years, cementless total hip arthroplasties, primary osteoarthritis diagnosis, and exclusion of the well-known outlier implant ASR (articular surface replacement). The primary outcome was revision for any reason. A meta-analysis of survival probabilities was performed with use of a fixed-effects model. Metal-on-metal implants with a large head size of36 mm were compared with metal-on-highly cross-linked polyethylene implants.Metal-on-metal implants with a large head size of36 mm were used in 5172 hips and metal-on-highly cross-linked polyethylene implants were used in 14,372 hips. Metal-on-metal total hip replacements with a large head size of36 mm had an increased risk of revision compared with metal-on-highly cross-linked polyethylene total hip replacements with more than two years of follow-up, with no difference during the first two years after implantation. The results of the hazard ratios (and 95% confidence intervals) from the multivariable model at various durations of follow-up were 0.95 (0.74 to 1.23) at zero to two years (p = 0.698), 1.42 (1.16 to 1.75) at more than two years to four years (p = 0.001), 1.78 (1.45 to 2.19) at more than four years to six years (p0.001), and 2.15 (1.63 to 2.83) at more than six years to seven years (p0.001).We conducted a comparison of large-head-size, metal-on-metal implants and metal-on-highly cross-linked polyethylene implants in younger patients with uncemented fixation. We found consistent and strong evidence worldwide that large-head-size, metal-on-metal implants were associated with increased risk of revision after two years compared with metal-on-highly cross-linked polyethylene implants, with the effect becoming more pronounced over time.

Objective We developed a personalized intervention for depressed patients with COPD (PID-C) aimed to mobilize patients to participate in the care of both conditions. We showed that PID-C reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks. This study focused on untangling key therapeutic ingredients of PID-C. Design Randomized controlled trial. Setting Community. Participants 138 patients who received the diagnoses of COPD and major depression after screening 898 consecutive admissions for acute inpatient pulmonary rehabilitation. Intervention Nine sessions of PID-C compared with usual care over 28 weeks. Measurements Primary outcome measures were the 17-item Hamilton Depression Rating Scale and the Pulmonary Functional Status and Dyspnea Questionnaire–Modified. Other measures were adherence to rehabilitation exercise (≥2 hours per week) and adherence to adequate antidepressant prescriptions. Results Low severity of dyspnea-related disability and adherence to antidepressants predicted subsequent improvement of depression. Exercise and low depression severity predicted improvement of dyspnea-related disability. Conclusions PID-C led to an interacting spiral of improvement in both depression and disability in a gravely medically ill population with a 17% mortality rate over 28 weeks and an expected deterioration in disability. The interrelationship of the course of depression and dyspnea-related disability underscores the need to target adherence to both antidepressants and chronic obstructive pulmonary disease rehabilitation. PID-C may serve as a care management model for depressed persons suffering from medical illnesses with a deteriorating course.

Objective Engage grew out of the need for streamlined psychotherapies that can be accurately used by community therapists in late-life depression. Engage was based on the view that dysfunction of reward networks is the principal mechanism mediating depressive symptoms. Accordingly, Engage uses “reward exposure” (exposure to meaningful activities) and assumes that repeated activation of reward networks will normalize these systems. This study examined whether change in a behavioral activation scale, an index of reward system function, predicts change in depressive symptomatology. Methods The participants (N = 48) were older adults with major depression treated with 9 weekly sessions of Engage and assessed 27 weeks after treatment. Depression was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the four subscales of Behavioral Activation for Depression Scale (activation, avoidance/rumination, work impairment, social impairment) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. Results Change only in the Activation subscale during successive periods of assessment predicted depression severity (HAM-D) at the end of each period (F 1, 47 = 21.05, p Limitations No comparison group. Partial overlap of Activation Subscale with HAM-D, lack of detailed neurocognitive assessment and social support. Conclusion Change in behavioral activation predicts improvement of depressive symptoms and signs in depressed older adults treated with Engage.

Background: GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) γ-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy ( 1 H MRS). Methods: Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with 1 H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%–120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W). Results: Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS. Limitations: The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. Conclusion: These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples.

Objective Engage is a treatment for late-life depression developed to match the skills of community clinicians based on the theory that dysfunction in the Research Domain Criteria Project positive valence systems is a critical mechanism of late-life depression. Accordingly, it uses "reward exposure" (engagement in meaningful, rewarding activities) as its principal intervention. This study tests the hypothesis that change in behavioral activation, an index of positive valence systems function, during successive treatment periods with Engage and during follow-up predicts depression at the end of each period. Methods Forty-eight nondemented, older adults with unipolar major depression were treated openly with 9 weekly sessions of Engage and assessed 36 weeks after entry. Depression severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the Behavioral Activation for Depression Scale (BADS) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. Results A mixed-effects model examined whether change in BADS in successive periods occurring during Engage treatment and during follow-up predicts depression at the end of each period. Both BADS change (F 1,52 = 18.63, p 2,52 = 7.68, p = 0.0012) predicted HAM-D scores at the end of each observation period. Every point of increase in BADS change reduced the HAM-D by 0.105 points. HAM-D at each point did not predict subsequent change in BADS (F 1,52 = 2.17, p = 0.146). Conclusion During Engage treatment and follow-up, change in behavioral activation is followed by improvement of depressive symptoms and signs.

Purpose: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk. Experimental Design: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk. We also investigated associations between SNPs in genes (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT, and in DHT metabolism and PCA risk. The population consisted of 426 men (205 controls and 221 cases) who underwent prostate-specific antigen screening as part of a PCA early detection program in Tyrol, Austria. Results: No association between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95% confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13). Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when compared with men carrying neither (P = 0.005). Controls with the AA genotype on rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03). Conclusions: This is the first study to implicate the 5α-reductase isoform 1 (SRD5A1) and PCA risk, supporting the rationale of blocking enzymatic activity of both isoforms of 5α-reductase for PCA chemoprevention. Cancer Epidemiol Biomarkers Prev; 19(1); 229–39

Nonadherence to antidepressant medication is common and leads to poor outcomes. Early nonadherence is especially problematic.To test the effectiveness of a psychosocial intervention to improve early adherence among older patients whose primary care physician newly initiated an antidepressant for depression.The Treatment Initiation and Participation Program (TIP) was offered in a 2-site randomized clinical effectiveness study between January 2011 and December 2014 at primary care practices in New York, New York, and Ann Arbor, Michigan. Analyses began in February 2016. All participants were middle-aged and older adults (aged ≥55 years) who received newly initiated depression treatment by their primary care physician and recruited within 10 days of their prescription. Analyses were intention-to-treat.Participants were randomly assigned to the intervention (TIP) or treatment as usual. Participants in the TIP group identified and addressed barriers to adherence, including stigma, misconceptions, and fears about treatment, before developing a personalized adherence strategy. The Treatment Initiation and Participation Program was delivered in three 30-minute contacts scheduled during a 6-week period just after the antidepressant was prescribed.The primary outcome was self-reported adherence on the Brief Medication Questionnaire, with adequate early adherence defined as taking 80% or more of the prescribed doses at 6 and 12 weeks. The secondary outcome was depression severity.In total, 231 middle-aged and older adults (167 women [72.3%] and 64 men [27.7%]) without significant cognitive impairment were randomly assigned to the TIP intervention (n = 115) or treatment as usual (n = 116). Participants had a mean (SD) age of 67.3 (8.4) years. Participants in the TIP group were 5 times more likely to be adherent at 6 weeks (odds ratio, 5.54; 95% CI, 2.57 to 11.96; χ21 = 19.05; P .001) and 3 times more likely to be adherent at both 6 and 12 weeks (odds ratio, 3.27; 95% CI, 1.73 to 6.17; χ21 = 13.34; P .001). Participants in the TIP group showed a significant earlier reduction (24.9%) in depressive symptoms (95% CI, 13.9 to 35.9; t337 = 4.46; adjusted P .001). In both groups, participants who were 80% adherent at weeks 6 and 12 had a 15% greater improvement in depressive symptoms from baseline over the course of treatment (95% CI, -0.2 to -30; t369 = 1.93; P = .051).The Treatment Initiation and Participation Program is an effective intervention to improve early adherence to pharmacotherapy. Improved adherence can promote improvement in depression.clinicaltrials.gov Identifier: NCT01301859.

OBJECTIVE: Depression screening has been widely implemented in community settings to increase detection of late-life depression. However, the rates of treatment initiation are low without additional structured follow-up. The current study evaluates the effectiveness of a brief psychosocial intervention, Open Door, designed to improve initiation of mental health treatment among clients of aging service meals programs. DESIGN: Older adult social service clients with depressive symptoms were randomized to either the Open Door intervention or a Service Referral control condition. In Open Door, the counselor collaborates with the client to identify and address both attitudinal and structural barriers to seeking mental health treatment. Independent research assessments were conducted 12 and 24 weeks after baseline to document treatment initiation (at least one session). RESULTS: At follow up, 64.6% (104/161) of participants had initiated a provider visit. Participants in Open Door participants were more likely to initiate treatment compared to those adults in the control condition (χ(2)=5.83, df=2, p=.016). Among participants with at least mild depressive symptoms, Open Door remained significantly more effective than the control condition (p

Background.Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram.Method.We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale – Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks.Results.There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = −2.09, df = 331, p = 0.0375) and the Reward-Related (t = −2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster.Conclusions.Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

ObjectiveTo test the hypotheses that (1) clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in reducing depressive symptoms of depressed, disabled, impoverished patients and that (2) development of problem-solving skills mediates improvement of depression.MethodsThis randomized clinical trial with a parallel design allocated participants to CM or CM-PST at 1:1 ratio. Raters were blind to patients' assignments. Two hundred seventy-one individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST. Participants were at least 60 years old with major depression measured with the 24-item Hamilton Depression Rating Scale (HAM-D), had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties' median.ResultsCM and CM-PST led to similar declines in HAM-D over 12 weeks (t = 0.37, df = 547, p = 0.71); CM was noninferior to CM-PST. The entire study group (CM plus CM-PST) had a 9.6-point decline in HAM-D (t = 18.7, df = 547, p

Background: Fixation in total hip replacements remains a controversial topic, despite the high level of its success. Data obtained from major orthopaedic registries indicate that there are large differences among preferred fixation and survival results. Methods: Using a distributed registry data network, primary total hip arthroplasties performed for osteoarthritis from 2001 to 2010 were identified from six national and regional total joint arthroplasty registries. A multivariate meta-analysis was performed using linear mixed models with the primary outcome revision for any reason. Survival probabilities and their standard errors were extracted from each registry for each unique combination of the covariates. Fixation strategies were compared with regard to age group, sex, bearing, and femoral-head diameter. All comparisons were based on the random-effects model and the fixed-effects model. Results: In patients who were seventy-five years of age and older, uncemented fixation had a significantly higher risk of revision (p < 0.001) than hybrid fixation, with a hazard ratio of 1.575 (95% confidence interval, 1.389 to 1.786). We found a similar, if lesser, effect in the intermediate age group of sixty-five to seventy-four years (hazard ratio, 1.16 [95% confidence interval, 1.023 to 1.315]; p = 0.021) and in the younger age group of forty-five to sixty-four years (hazard ratio, 1.205 [95% confidence interval, 1.008 to 1.442]; p = 0.041). There were no significant differences between hybrid and cemented bearings across age groups. Conclusions: We conclude that cementless fixation should be avoided in older patients (those seventy-five years of age or older), although this evidence is less strong in patients of intermediate and younger ages.

Posterior-stabilized total knee prostheses were introduced to address instability secondary to loss of posterior cruciate ligament function, and they have either fixed or mobile bearings. Mobile bearings were developed to improve the function and longevity of total knee prostheses. In this study, the International Consortium of Orthopaedic Registries used a distributed health data network to study a large cohort of posterior-stabilized prostheses to determine if the outcome of a posterior-stabilized total knee prosthesis differs depending on whether it has a fixed or mobile-bearing design.Aggregated registry data were collected with a distributed health data network that was developed by the International Consortium of Orthopaedic Registries to reduce barriers to participation (e.g., security, proprietary, legal, and privacy issues) that have the potential to occur with the alternate centralized data warehouse approach. A distributed health data network is a decentralized model that allows secure storage and analysis of data from different registries. Each registry provided data on mobile and fixed-bearing posterior-stabilized prostheses implanted between 2001 and 2010. Only prostheses associated with primary total knee arthroplasties performed for the treatment of osteoarthritis were included. Prostheses with all types of fixation were included except for those with the rarely used reverse hybrid (cementless tibial and cemented femoral components) fixation. The use of patellar resurfacing was reported. The outcome of interest was time to first revision (for any reason). Multivariate meta-analysis was performed with linear mixed models with survival probability as the unit of analysis.This study includes 137,616 posterior-stabilized knee prostheses; 62% were in female patients, and 17.6% had a mobile bearing. The results of the fixed-effects model indicate that in the first year the mobile-bearing posterior-stabilized prostheses had a significantly higher hazard ratio (1.86) than did the fixed-bearing posterior-stabilized prostheses (95% confidence interval, 1.28 to 2.7; p = 0.001). For all other time intervals, the mobile-bearing posterior-stabilized prostheses had higher hazard ratios; however, these differences were not significant.Mobile-bearing posterior-stabilized prostheses had an increased rate of revision compared with fixed-bearing posterior-stabilized prostheses. This difference was evident in the first year.

Summary Objective Hospital crossover occurs when people seek care at multiple hospitals, creating information gaps for physicians at the time of care. Health information exchange (HIE) is technology that fills these gaps, by allowing otherwise unaffiliated physicians to share electronic medical information. However, the potential value of HIE is understudied, particularly for chronic neurologic conditions like epilepsy. We describe the prevalence and associated factors of hospital crossover among people with epilepsy, in order to understand the epidemiology of who may benefit from HIE. Methods We used a cross-sectional study design to examine the bivariate and multivariable association of demographics, comorbidity, and health service utilization variables with hospital crossover, among people with epilepsy. We identified 8,074 people with epilepsy from the International Classification of Diseases, Ninth Revision (ICD-9) codes, obtained from an HIE that linked seven hospitals in Manhattan, New York. We defined hospital crossover as care from more than one hospital in any setting (inpatient, outpatient, emergency, or radiology) over 2 years. Results Of 8,074 people with epilepsy, 1,770 (22%) engaged in hospital crossover over 2 years. Crossover was associated with younger age (children compared with adults, adjusted odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2–1.7), living near the hospitals (Manhattan vs. other boroughs of New York City, adjusted OR 1.6, 95% CI 1.4–1.8), more visits in the emergency, radiology, inpatient, and outpatient settings (p

Objective Executive dysfunction may play a key role in the pathophysiology of late-life depression. Executive dysfunction can be assessed with cognitive tests and subjective report of difficulties with executive skills. The present study investigated the association between subjective report of executive functioning complaints and time to escitalopram treatment response in older adults with major depressive disorder (MDD). Methods 100 older adults with MDD (58 with executive functioning complaints and 42 without executive functioning complaints) completed a 12-week trial of escitalopram. Treatment response over 12 weeks, as measured by repeated Hamilton Depression Rating Scale scores, was compared for adults with and without executive complaints using mixed-effects modeling. Results Mixed effects analysis revealed a significant group × time interaction, F (1, 523.34) = 6.00, p = 0.01. Depressed older adults who reported executive functioning complaints at baseline demonstrated a slower response to escitalopram treatment than those without executive functioning complaints. Conclusion Self-report of executive functioning difficulties may be a useful prognostic indicator for subsequent speed of response to antidepressant medication.

Background The impact of anesthetic technique on perioperative outcomes remains controversial. We studied a large national sample of primary joint arthroplasty recipients and hypothesized that neuraxial anesthesia favorably influences perioperative outcomes. Methods Data from approximately 400 hospitals between 2006 and 2010 were accessed. Patients who underwent primary hip or knee arthroplasty were identified and subgrouped by anesthesia technique: general, neuraxial, and combined neuraxial–general. Demographics, postoperative complications, 30-day mortality, length of stay, and patient cost were analyzed and compared. Multivariable analyses were conducted to identify the independent impact of choice of anesthetic on outcomes. Results Of 528,495 entries of patients undergoing primary hip or knee arthroplasty, information on anesthesia type was available for 382,236 (71.4%) records. Eleven percent were performed under neuraxial, 14.2% under combined neuraxial–general, and 74.8% under general anesthesia. Average age and comorbidity burden differed modestly between groups. When neuraxial anesthesia was used, 30-day mortality was significantly lower (0.10, 0.10, and 0.18%; P < 0.001), as was the incidence of prolonged (>75th percentile) length of stay, increased cost, and in-hospital complications. In the multivariable regression, neuraxial anesthesia was associated with the most favorable complication risk profile. Thirty-day mortality remained significantly higher in the general compared with the neuraxial or neuraxial–general group for total knee arthroplasty (adjusted odds ratio [OR] of 1.83, 95% CI 1.08–3.1, P = 0.02; OR of 1.70, 95% CI 1.06–2.74, P = 0.02, respectively). Conclusions The utilization of neuraxial versus general anesthesia for primary joint arthroplasty is associated with superior perioperative outcomes. More research is needed to study potential mechanisms for these findings.

Androgen receptor signaling plays a critical role in prostate cancer pathogenesis. Yet, the regulation of androgen receptor signaling remains elusive. Even with stringent androgen deprivation therapy, androgen receptor signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptor signaling. We examined primary and metastatic prostate cancer and found that miR-31 expression was reduced as a result of promoter hypermethylation, and importantly, the levels of miR-31 expression were inversely correlated with the aggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and androgen receptor could mutually repress each other. Upregulation of miR-31 effectively suppressed androgen receptor expression through multiple mechanisms and inhibited prostate cancer growth in vivo. Notably, we found that miR-31 targeted androgen receptor directly at a site located in the coding region, which was commonly mutated in prostate cancer. In addition, miR-31 suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel androgen receptor regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker. Cancer Res; 73(3); 1232–44. ©2012 AACR.

Prostate cancer is the second leading cause of cancer-related death among men in the USA1. Up to 30% of men with clinically localized prostate cancer will progress to metastatic disease, but the genetic and molecular changes involved in prostate cancer progression are still largely unknown. Certain subtypes of clinically significant prostate cancer are remarkably aggressive, rapidly progressing toward metastatic and therapy resistant disease. However, there is also a large proportion of relatively indolent disease. Many experts believe that the vast majority of men will die with prostate cancer rather than from it, and that over-treatment of more indolent prostate cancer with radical therapy is a major source of morbidity. These points demonstrate a critical need for biomarkers of aggressive prostate cancer that correlate with prognosis. Currently, the only routinely used biomarker for prostate cancer is PSA. However, the value of PSA for the detection of clinically significant prostate cancer is highly controversial2,3. Furthermore, other methods to distinguish aggressive from indolent disease are limited. The identification of biomarkers for aggressive prostate cancer could help to achieve a molecular classification of prostate cancer, distinguishing indolent from aggressive cases – the paradigm of personalized medicine. The advent of next-generation RNA and DNA sequencing provides an unprecedented opportunity for the discovery of novel mutations4 and gene fusions5,6. The Cancer Genome Atlas (TCGA) program participates in the International Cancer Genome Consortium (www.icgc.org) to discover genetic changes in cancer genome by full-scale genome sequencing. This requires well-characterized and high-quality human biospecimens. Therefore, fresh tissue, as well as blood and urine, must be optimally processed and stored to preserve molecular contents (DNA, RNA, and proteins). Historically, tumor-derived prostate cancer cells are difficult to maintain in culture, leading to a greater dependence on tissue sample quality and availability for research purposes. However, identifying tumor and obtaining large quantities of high-quality specimens at the time of processing while not compromising patient care poses a challenge due to the multifocal and heterogeneous nature of the disease. To address this need, we have modified a previously published protocol developed as a part of the National Cancer Institute funded Prostate SPORE program at the University of Michgian7. The biobanking Standard Operating Procedures (SOPs) are performed within the framework of the Weill Cornell Medical College (WCMC) Institutional Biobank8. We describe SOPs, quality assessment of samples procured, and clinical impact on 105 consecutive patients who underwent radical prostatectomy (RP).

Copy number variants (CNVs) are a recently recognized class of human germ line polymorphisms and are associated with a variety of human diseases, including cancer. Because of the strong genetic influence on prostate cancer, we sought to identify functionally active CNVs associated with susceptibility of this cancer type. We queried low-frequency biallelic CNVs from 1,903 men of Caucasian origin enrolled in the Tyrol Prostate Specific Antigen Screening Cohort and discovered two CNVs strongly associated with prostate cancer risk. The first risk locus ( P = 7.7 × 10 −4 , odds ratio = 2.78) maps to 15q21.3 and overlaps a noncoding enhancer element that contains multiple activator protein 1 (AP-1) transcription factor binding sites. Chromosome conformation capture (Hi-C) data suggested direct cis -interactions with distant genes. The second risk locus ( P = 2.6 × 10 −3 , odds ratio = 4.8) maps to the α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase C ( MGAT4C ) gene on 12q21.31. In vitro cell-line assays found this gene to significantly modulate cell proliferation and migration in both benign and cancer prostate cells. Furthermore, MGAT4C was significantly overexpressed in metastatic versus localized prostate cancer. These two risk associations were replicated in an independent PSA-screened cohort of 800 men (15q21.3, combined P = 0.006; 12q21.31, combined P = 0.026). These findings establish noncoding and coding germ line CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression.

Although recurrent gene fusions involving erythroblastosis virus E26 transformation-specific (ETS) family transcription factors are common in prostate cancer, their products are considered 'undruggable' by conventional approaches. Recently, rare targetable gene fusions involving the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, have been identified in 1-5% of lung cancers, suggesting that similar rare gene fusions may occur in other common epithelial cancers, including prostate cancer. Here we used paired-end transcriptome sequencing to screen ETS rearrangement-negative prostate cancers for targetable gene fusions and identified the SLC45A3-BRAF (solute carrier family 45, member 3-v-raf murine sarcoma viral oncogene homolog B1) and ESRP1-RAF1 (epithelial splicing regulatory protein-1-v-raf-1 murine leukemia viral oncogene homolog-1) gene fusions. Expression of SLC45A3-BRAF or ESRP1-RAF1 in prostate cells induced a neoplastic phenotype that was sensitive to RAF and mitogen-activated protein kinase kinase (MAP2K1) inhibitors. Screening a large cohort of patients, we found that, although rare, recurrent rearrangements in the RAF pathway tend to occur in advanced prostate cancers, gastric cancers and melanoma. Taken together, our results emphasize the key role of RAF family gene rearrangements in cancer, suggest that RAF and MEK inhibitors may be useful in a subset of gene fusion-harboring solid tumors and demonstrate that sequencing of tumor transcriptomes and genomes may lead to the identification of rare targetable fusions across cancer types.

We develop hierarchical generalized linear models and computationally efficient algorithms for genomewide analysis of quantitative trait loci (QTL) for various types of phenotypes in experimental crosses. The proposed models can fit a large number of effects, including covariates, main effects of numerous loci, and gene–gene (epistasis) and gene–environment (G × E) interactions. The key to the approach is the use of continuous prior distribution on coefficients that favors sparseness in the fitted model and facilitates computation. We develop a fast expectation-maximization (EM) algorithm to fit models by estimating posterior modes of coefficients. We incorporate our algorithm into the iteratively weighted least squares for classical generalized linear models as implemented in the package R. We propose a model search strategy to build a parsimonious model. Our method takes advantage of the special correlation structure in QTL data. Simulation studies demonstrate reasonable power to detect true effects, while controlling the rate of false positives. We illustrate with three real data sets and compare our method to existing methods for multiple-QTL mapping. Our method has been implemented in our freely available package R/qtlbim (www.qtlbim.org), providing a valuable addition to our previous Markov chain Monte Carlo (MCMC) approach.

Importance Among older home health care patients, depression is highly prevalent, is often inadequately treated, and contributes to hospitalization and other poor outcomes. Feasible and effective interventions are needed to reduce this burden of depression. Objective To determine whether, among older Medicare Home Health recipients who screen positive for depression, patients of nurses receiving randomization to an intervention have greater improvement in depressive symptoms during 1 year than patients receiving enhanced usual care. Design, Setting, and Participants This cluster randomized effectiveness trial conducted at 6 home health care agencies nationwide assigned nurse teams to an intervention (12 teams) or to enhanced usual care (9 teams). Between January 13, 2009, and December 6, 2012, Medicare Home Health patients 65 years and older who screened positive for depression on routine nursing assessments were recruited, underwent assessment, and were followed up at 3, 6, and 12 months by research staff blinded to intervention status. Patients were interviewed at home and by telephone. Of 502 eligible patients, 306 enrolled in the study. Interventions The Depression Care for Patients at Home (Depression CAREPATH) trial requires nurses to manage depression at routine home visits by weekly symptom assessment, medication management, care coordination, education, and goal setting. Nurses’ training totaled 7 hours (4 onsite and 3 via the web). Researchers telephoned intervention team supervisors every other week. Main Outcomes and Measures Depression severity, assessed by the 24-item Hamilton Scale for Depression (HAM-D). Results The 306 participants were predominantly female (69.6%), were racially/ethnically diverse (18.0% black and 16.0% Hispanic), and had a mean (SD) age of 76.5 (8.0) years. In the full sample, the intervention had no effect ( P = .13 for intervention × time interaction). Adjusted HAM-D scores (Depression CAREPATH vs control) did not differ at 3 months (10.5 vs 11.4, P = .26) or at 6 months (9.3 vs 10.5, P = .12) but reached significance at 12 months (8.7 vs 10.6, P = .05). In the subsample with mild depression (HAM-D score, P = .90), and HAM-D scores did not differ at any follow-up points. Among 208 participants with a HAM-D score of 10 or higher, the Depression CAREPATH demonstrated effectiveness ( P = .02), with lower HAM-D scores at 3 months (14.1 vs 16.1, P = .04), at 6 months (12.0 vs 14.7, P = .02), and at 12 months (11.8 vs 15.7, P = .005). Conclusion and Relevance Home health care nurses can effectively integrate depression care management into routine practice. However, the clinical benefit seems to be limited to patients with moderate to severe depression. Trial Registration clinicaltrials.gov Identifier:NCT01979302