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Income-based differences in the use of and outcomes in TKA have been studied; however, it is not known if different healthcare systems affect this relationship. Although Canada's single-payer healthcare system is assumed to attenuate the wealth-based differences in TKA use observed in the United States, empirical cross-border comparisons are lacking.(1) Does TKA use differ between Pennsylvania, USA, and Ontario, Canada? (2) Are income-based disparities in TKA use larger in Pennsylvania or Ontario? (3) Are TKA outcomes (90-day mortality, 90-day readmission, and 1-year revision rates) different between Pennsylvania and Ontario? (4) Are income-based disparities in TKA outcomes larger in Pennsylvania or Ontario?We identified all patients hospitalized for primary TKA in this cross-border retrospective analysis, using administrative data for 2012 to 2018, and we found a total of 161,244 primary TKAs in Ontario and 208,016 TKAs in Pennsylvania. We used data from the Pennsylvania Health Care Cost Containment Council, Harrisburg, PA, USA, and the ICES (formally the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada. We linked patient-level data to the respective census data to determine community-level income using ZIP Code or postal code of residence and stratified patients into neighborhood income quintiles. We compared TKA use (age and gender, standardized per 10,000 population per year) for patients residing in the highest-income versus the lowest-income quintile neighborhoods. Similarly secondary outcomes 90-day mortality, 90-day readmission, and 1-year revision rates were compared between the two regions and analyzed by income groups.TKA use was higher in Pennsylvania than in Ontario overall and for all income quintiles (lowest income quartile: 31 versus 18 procedures per 10,000 population per year; p0.001; highest income quartile: 38 versus 23 procedures per 10,000 population per year; p0.001). The relative difference in use between the highest-income and lowest-income quintile was larger in Ontario (28% higher) than in Pennsylvania (23% higher); p0.001. Patients receiving TKA in Pennsylvania were more likely to be readmitted within 90 days and were more likely to undergo revision within the first year than patients in Ontario, but there was no difference in mortality at 1 year. When comparing income groups, there were no differences between the countries in 90-day mortality, readmission, or 1-year revision rates (p0.05).These results suggest that universal health insurance through a single-payer may not reduce the income-based differences in TKA access that are known to exist in the United States. Future studies are needed determine if our results are consistent across other geographic regions and other surgical procedures.Level III, therapeutic study.

Figure S5 - PDF file 224K, Toxicity studies in mice

Figures S7, S8 and S9 - PDF file 206K, SMAD1 expression in patients and functional experiments

Supplementary Methods - PDF file 100K, Reagents, gene expression profiling, RT-PCR, mice studies, clinical trial, patient samples, ex vivo treatments, immunohistochemistry and statistical analysis

Table S2 - PDF file 62K, Genes hypermethylated and repressed in doxorubicin resistant cell lines

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

Supplementary Tables 1-2, Supplementary Figures 1-2 from Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer

PDF file - 146K, Supplementary Table S1. Differentially expressed 105 miRNAs in PCA. Supplementary Table S2. List of 25 miRNAs differentially expressed with at least 1.5 fold change in PCA. Supplementary Table S3. List of CpG sites examined by MassARRAY EpiTyping. Supplementary Tables S4. Statistic analysis of DNA methylation levels of the miR-31 promoter in matched samples. Supplementary Tables S5. Statistic analysis of DNA methylation levels of the miR-31 promoter in clinical PCA samples. Supplementary Table S6. Top 5 cellular processes altered by miR-31 in LNCaP cells.

PDF file - 134K

PDF file - 1891K, Supplementary Fig. S1. Identification of 105 differential expressed miRNAs in PCA, deletion analysis for Chr. 9p21.3, and DNA methylation analysis of the miR-31 promoter region Supplementary Fig. S2. AR-signaling negatively regulates the expression of miR-31. Supplementary Fig. S3. miR-31 negatively regulates AR and E2F1. Supplementary Fig. S4. miR-31 directly targets key cell cycle players. Supplementary Fig. S5. miR-31 inhibits growth the VCaP xenografts.

Background The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status. Objective To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults. Design We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI. Participants Two hundred twenty-nine study participants at a major academic medical center. Main Measures We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI. Key Results In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9–89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46–0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians’ clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result. Conclusions Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07265-8.

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.

Suicide is a leading cause of death in the US. Patients with pain conditions have higher suicidal risks. In a systematic review searching observational studies from multiple sources (e.g., MEDLINE) from 1 January 2000–12 September 2020, we evaluated existing suicide prediction models’ (SPMs) performance and identified risk factors and their derived data sources among patients with pain conditions. The suicide-related outcomes included suicidal ideation, suicide attempts, suicide deaths, and suicide behaviors. Among the 87 studies included (with 8 SPM studies), 107 suicide risk factors (grouped into 27 categories) were identified. The most frequently occurring risk factor category was depression and their severity (33%). Approximately 20% of the risk factor categories would require identification from data sources beyond structured data (e.g., clinical notes). For 8 SPM studies (only 2 performing validation), the reported prediction metrics/performance varied: C-statistics (n = 3 studies) ranged 0.67–0.84, overall accuracy(n = 5): 0.78–0.96, sensitivity(n = 2): 0.65–0.91, and positive predictive values(n = 3): 0.01–0.43. Using the modified Quality in Prognosis Studies tool to assess the risk of biases, four SPM studies had moderate-to-high risk of biases. This systematic review identified a comprehensive list of risk factors that may improve predicting suicidal risks for patients with pain conditions. Future studies need to examine reasons for performance variations and SPM’s clinical utility.

BackgroundMultiple policy initiatives encourage more cautious prescribing of opioids in light of their risks. Electronic health record (EHR) redesign can influence prescriber choices, but some redesigns add to workload.ObjectiveTo estimate the effect of an EHR prescribing redesign on both opioid prescribing choices and keystrokes.DesignQuality improvement quasi-experiment, analyzed as interrupted time series.ParticipantsAdult patients of an academic multispecialty practice and a federally qualified health center (FQHC) who received new prescriptions for short-acting opioids, and their providers.InterventionIn the redesign, new prescriptions of short-acting opioids defaulted to the CDC-recommended minimum for opioid-naïve patients, with no alerts or hard stops, such that 9 keystrokes were required for a guideline-concordant prescription and 24 for a non-concordant prescription.Main MeasuresProportion of guideline-concordant prescriptions, defined as new prescriptions with a 3-day supply or less, calculated per 2-week period. Number of mouse clicks and keystrokes needed to place prescriptions.Key ResultsAcross the 2 sites, 22,113 patients received a new short-acting opioid prescription from 821 providers. Before the intervention, both settings showed secular trends toward smaller-quantity prescriptions. At the academic practice, the intervention was associated with an immediate increase in guideline-concordant prescriptions from an average of 12% to 31% of all prescriptions. At the FQHC, about 44% of prescriptions were concordant at the time of the intervention, which was not associated with an additional significant increase. However, total keystrokes needed to place the concordant prescriptions decreased 62.7% from 3552 in the 6 months before the intervention to 1323 in the 6 months afterwards.ConclusionsAutocompleting prescription forms with guideline-recommended values was associated with a large increase in guideline concordance in an organization where baseline concordance was low, but not in an organization where it was already high. The redesign markedly reduced the number of keystrokes needed to place orders, with important implications for EHR-related stress.Trial Registrationwww.ClinicalTrials.gov protocol 1710018646

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.

Effective psychotherapies for late-life depression are underutilized, mainly because of their complexity. “Engage” is a novel, streamlined psychotherapy that relies on neurobiology to identify core behavioral pathology of late-life depression and targets it with simple interventions, co-designed with community therapists so that they can be delivered in community settings. Consecutively recruited adults (≥60 years) with major depression (n = 249) were randomly assigned to 9 weekly sessions of “Engage” or to the evidence-based Problem-Solving Therapy (PST) offered by 35 trained community social workers and assessed by blind raters. “Engage” therapists required an average of 30% less training time to achieve fidelity to treatment than PST therapists and had one-third of the PST therapists’ skill drift. Both treatments led to reduction of HAM-D scores over 9 weeks. The mixed effects model-estimated HAM-D ratings were not significantly different between the two treatments at any assessment point of the trial. The one-sided 95% CI for treatment-end difference was (−∞, 0.07) HAM-D points, indicating a non-inferiority margin of 1.3 HAM-D points or greater; this margin is lower than the pre-determined 2.2-point margin. The two treatment arms had similar response (HR = 1.08, 95% CI (0.76, 1.52), p = 0.67) and remission rates (HR = 0.89, 95% CI (0.57, 1.39), p = 0.61). We conclude that “Engage” is non-inferior to PST. If disseminated, “Engage” will increase the number of therapists who can reliably treat late-life depression and make effective psychotherapy available to large numbers of depressed older adults.

Although several risk calculators are available to determine risk for readmission following a heart failure (HF) hospitalization, none provide information on cause-specific readmission. Understanding risk for cause-specific readmission could aid in developing a targeted approach to reducing readmissions. We sought to determine if a simple cardiac co-morbidity count could identify individuals at high risk for a cardiovascular (CV) readmission following a HF hospitalization. Using the Nationwide Readmissions Database, we examined nonfatal hospital discharges with a principal diagnosis of HF. We calculated a 0 to 3 cardiac co-morbidity count based on the presence of coronary artery disease, atrial arrhythmia, and/or ventricular arrhythmia. We used a multinomial logistic regression to determine if the cardiac co-morbidity count was independently associated with CV readmission or non-CV readmission, adjusting for patient- and hospital-level confounders. In 380,075 discharges, 28% had a co-morbidity count of 0, 47% had a count of 1, 23% had a count of 2, and 2% had a count of 3. In a fully adjusted model, cardiac co-morbidity count was independently associated with CV readmission: compared with individuals with a count of 0, the relative risk for those with a count of 1 was 1.27 (95% confidence interval [CI]: 1.23 to 1.31); for those with a count of 2 was 1.40 (95% CI: 1.35 to 1.46); and for those with a count of 3 was 1.36 (95% CI: 1.23 to 1.51). Cardiac co-morbidity count was not independently associated with non-CV readmission. In conclusion, we found that a simple cardiac co-morbidity count was independently associated with increased risk of CV but not non-CV readmission.

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

Introduction: Allostatic load (AL) is the physiologic “wear and tear” on the body from adapting to stress. AL is associated with mortality for diseases including cancer and diabetes. While stress has been implicated in the development of heart failure (HF), no studies have studied the association between AL and HF. Hypothesis: Higher allostatic load is associated with incident HF events. Methods: We examined 16,765 participants without suspected HF at baseline from the REGARDS cohort. The main exposure was AL score quartile. AL score was based on baseline heart rate, systolic blood pressure (BP), diastolic BP, waist circumference, glucose, total cholesterol, high density lipoprotein cholesterol, albumin, c-reactive protein, urine albumin to creatinine ratio, and cystatin C. Each parameter was assigned points (0-3) based on quartiles within the sample, and total AL score ranged from 0-33. The main outcome was incident HF hospitalization or HF death. Cox proportional hazards models were adjusted for baseline demographics, geographic residence, socioeconomic factors, and lifestyle/health habits. Results: The mean age of the sample was 64 + 9.6 years, 61.5% were women, and 38.7% were Black individuals. Over a mean follow up of 9.9 years, there were 750 HF events (635 incident HF hospitalizations and 115 incident HF deaths). AL score Q1 included scores 1-12, Q2 13-16, Q3 17-20, and Q4 21-33 (Figure). Compared to Q1, hazards for incident HF event increased with AL quartile (Q2 HR 1.29, 95% CI 0.93-1.79; Q3 HR 2.06, 95% CI 1.51-2.81; Q4 HR 3.65, 95% CI 2.68-4.97) in a fully adjusted model. Conclusion: AL was associated with incident HF events. This study supports a relationship between physiologic dysregulation due to maladaptive stress response and the development of HF.

This study aimed to identify subgroups of depressed older adults with distinct trajectories of suicidal ideation during brief psychotherapy and to detect modifiable predictors of membership to the trajectories of suicidal ideation. Latent growth mixed models were used to identify trajectories of the presence of suicidal ideation in participants to a randomized controlled trial comparing Problem Solving Therapy with “Engage” therapy in older adults with major depression over 9 weeks. Predictors of membership to trajectories of suicidal ideation were identified by the convergence of four machine learning models, i.e., least absolute shrinkage and selection operator logistic regression, random forest, gradient boosting machine, and classification tree. The course of suicidal ideation was best captured by two trajectories, a favorable and an unfavorable trajectory comprising 173 and 76 participants respectively. Members of the favorable trajectory had no suicidal ideation by week 8. In contrast, members of the unfavorable trajectory had a 60% probability of suicidal ideation by treatment end. Convergent findings of the four machine learning models identified hopelessness, neuroticism, and low general self-efficacy as the strongest predictors of membership to the unfavorable trajectory of suicidal ideation during psychotherapy. Assessment of suicide risk should include hopelessness, neuroticism, and general self-efficacy as they are predictors of an unfavorable course of suicidal ideation in depressed older adults receiving psychotherapy. Psychotherapeutic interventions exist for hopelessness, emotional reactivity related to neuroticism, and low self-efficacy, and if used during therapy, may improve the course of suicidal ideation.

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.

Late-life depression is heterogenous and patients vary in disease course over time. Most psychotherapy studies measure activity levels and symptoms solely using self-report scales, administered periodically. These scales may not capture granular changes during treatment. We introduce the potential utility of passive sensing data collected with smartphone to assess fluctuations in daily functioning in real time during psychotherapy for late life depression in elder abuse victims. To our knowledge, this is the first investigation of passive sensing among depressed elder abuse victims. We present data from three victims who received a 9-week intervention as part of a pilot randomized controlled trial and showed a significant decrease in depressive symptoms (50% reduction). Using a smartphone, we tracked participants' daily number of smartphone unlocks, time spent at home, time spent in conversation, and step count over treatment. Independent assessment of depressive symptoms and behavioral activation were collected at intake, Weeks 6 and 9. Data revealed patient-level fluctuations in activity level over treatment, corresponding with self-reported behavioral activation. We demonstrate how passive sensing data could expand our understanding of heterogenous presentations of late-life depression among elder abuse. We illustrate how trajectories of change in activity levels as measured with passive sensing and subjective measures can be tracked concurrently over time. We outline challenges and potential solutions for application of passive sensing data collection in future studies with larger samples using novel advanced statistical modeling, such as artificial intelligence algorithms.

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.

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.

OBJECTIVES To determine whether the number of medications taken by adults with heart failure (HF) and impairment in activities of daily living (ADL)—a subpopulation in whom the risks of a high medication burden may outweigh the benefits—differs from the number taken by those without impairment in ADLs. DESIGN Cross‐sectional. SETTING National Health and Nutrition Examination Survey (NHANES; 2003–2014), a cross‐sectional survey that produces national estimates of adults in the United States. PARTICIPANTS Adults aged 50 and older (mean 70) with self‐reported HF (N= 947; representing 4.6 million adults with HF in the United States. MEASURMENTS 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 oneself, 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 the complex survey design of NHANES. RESULTS Mean medication count was 7.2, and 74% of participants were taking 5 or more medications (polypharmacy). In a multivariable model, ADL impairment was not independently associated with medication count. These findings were similar for those with 3 or more 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 risk of adverse outcomes. J Am Geriatr Soc 67:284–291, 2019.

Introduction: The benefits of a healthy lifestyle in the context of a high disease and medication burden are not clear. Hypothesis: Healthy lifestyle is inversely associated with all-cause mortality among adults with high medication burden. Methods: We examined participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Exposure variables were 4 healthy behaviors: adherence to a Mediterranean diet, physical activity, smoking abstinence, and sedentary lifestyle avoidance (low TV time). Each behavior was scored from 0-2, where 0 indicated low adherence and 2 indicated high adherence. We also examined a cumulative Health Behavior Score (HBS) based on the sum of individual behavior scores (range 0-8). The main outcome was all-cause mortality. To examine the association between each behavior and mortality, we estimated Cox proportional hazards models for each medication burden stratum (no polypharmacy: 0-4 medications at baseline; polypharmacy: 5-9; hyperpolypharmacy: ≥ 10), adjusting for socio-demographics, health status, comorbid conditions, and medication adherence. Results: Among 20,417 participants (9.8 ± 3.8 years followup), mean age was 64.8 ± 9.2 years, and 56% were women. At baseline, 44% had no polypharmacy, 39% had polypharmacy, and 17% had hyperpolypharmacy. Mortality increased with increasing medication burden (no polypharmacy: 19.1%; polypharmacy: 29.7%; hyperpolypharmacy: 41.3%). The highest score for each behavior was inversely associated with all-cause mortality in all 3 strata. The highest HBS for each stratum conferred substantial benefit (no polypharmacy: HR 0.52 (95% CI 0.45-0.61); polypharmacy: HR 0.55 (95% CI 0.49-0.63); hyperpolypharmacy HR 0.69 (95% CI 0.58-0.82)) (Table). Conclusions: Healthy lifestyle was inversely associated with all-cause mortality irrespective of medication burden, supporting the value of healthy lifestyle counseling even among adults with high medication burden.

Mental health concerns, such as suicidal thoughts, are frequently documented by providers in clinical notes, as opposed to structured coded data. In this study, we evaluated weakly supervised methods for detecting “current” suicidal ideation from unstructured clinical notes in electronic health record (EHR) systems. Weakly supervised machine learning methods leverage imperfect labels for training, alleviating the burden of creating a large manually annotated dataset. After identifying a cohort of 600 patients at risk for suicidal ideation, we used a rule-based natural language processing approach (NLP) approach to label the training and validation notes (n = 17,978). Using this large corpus of clinical notes, we trained several statistical machine learning models—logistic classifier, support vector machines (SVM), Naive Bayes classifier—and one deep learning model, namely a text classification convolutional neural network (CNN), to be evaluated on a manually-reviewed test set (n = 837). The CNN model outperformed all other methods, achieving an overall accuracy of 94% and a F1-score of 0.82 on documents with “current” suicidal ideation. This algorithm correctly identified an additional 42 encounters and 9 patients indicative of suicidal ideation but missing a structured diagnosis code. When applied to a random subset of 5,000 clinical notes, the algorithm classified 0.46% (n = 23) for “current” suicidal ideation, of which 87% were truly indicative via manual review. Implementation of this approach for large-scale document screening may play an important role in point-of-care clinical information systems for targeted suicide prevention interventions and improve research on the pathways from ideation to attempt.

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.

Introduction: Major depressive disorder (MDD) is associated with hypothalamic-pituitary-adrenal axis dysfunction that may persist into remission. Preliminary evidence suggests that this dysfunction may be associated with impaired neuropsychological performance in remitted MDD. MDD with psychotic features (“psychotic depression”) is associated with greater neuropsychological and functional impairment than nonpsychotic depression, including in remission. Therefore, the aim of this exploratory study was to examine the relationships among hair cortisol concentration (HCC) – a marker of longer term endogenous cortisol exposure – and history of psychotic features, neuropsychological performance, and functioning in remitted MDD. Methods: This cross-sectional study compared the relationship between HCC and (i) history of psychosis, (ii) neuropsychological performance, and (iii) everyday functioning in a group of 60 participants with remitted later-life MDD using Pearson’s correlation coefficients. This study also measured HCC in a group of 36 nonpsychiatric volunteers to examine the clinical significance of HCC in the patient group. Results: There were no statistically significant correlations between HCC and history of psychotic features, neuropsychological performance, or functioning. Furthermore, there was no clinically meaningful difference in HCC between patients and nonpsychiatric volunteers. Conclusion: This study is the first to examine HCC in psychotic depression. The results do not support the hypothesis that impaired neuropsychological performance, and everyday function in remitted psychotic depression is due to a sustained elevation of cortisol.

Objective To characterize the US national level healthcare utilization patterns of patients with commercial insurance plans before and after a psychiatric hospitalization admitted through the emergency department (ED) using insurance claims data. Method We identified 34,250 patients from multiple commercial health insurance providers across the US who meet our eligibility criteria. We summarized their healthcare encounters and used logistic regression models to study the patterns of healthcare utilization including prior visits, outpatient follow-ups, and hospital- or ED-readmissions. Results Suicidal ideation was highly prevalent at the time of the index event (29.88%). Almost half of the patients (48.28%) had healthcare encounters with the same primary diagnosis one year before admission, about 5% had outpatient follow-ups or were readmitted to the hospital or ED 7 days post discharge. The post 30-day follow-ups and readmission rates were slightly higher. In general, older patients were less likely to have prior visits, follow-ups, or readmissions, and patients with SUDs, specifically alcohol dependence, opioid dependence/abuse, and stimulant dependence, were more likely to have outpatient follow-ups. Conclusion Patterns of patients' prior visits, follow-ups, and readmissions varied by demographics and psychiatric comorbidity. Additional studies are needed to further explain the spatial variations of utilization patterns.

The study aimed to: a) Identify distinct trajectories of change in depressive symptoms by mid-treatment during psychotherapy for late-life depression with executive dysfunction; b) examine if non-response by mid-treatment predicted poor response at treatment end; c) identify baseline characteristics predicting an early non-response trajectory by mid-treatment. A sample of 221 adults 60 years and older with major depression and executive dysfunction were randomized to 12 weeks of either Problem-Solving Therapy or Supportive Therapy. We used Latent Growth Mixture Models (LGMM) to detect subgroups with distinct trajectories of change in depression by mid-treatment (6th week). We conducted regression analyses with LGMM subgroups as predictors of response at treatment end. We used random forest machine learning algorithms to identify baseline predictors of LGMM trajectories. We found that approximately 77.5% of participants had a declining trajectory of depression in weeks 0–6, while the remaining 22.5% had a persisting depression trajectory, with no treatment differences. The LGMM trajectories predicted remission and response at treatment end. A random forests model with high prediction accuracy (80%) showed that the strongest modifiable predictors of the persisting depression trajectory were low perceived social support, followed by high neuroticism, low treatment expectancy, and low perception of the therapist as accepting. Our results suggest that modifiable risk factors of early non-response to psychotherapy can be identified at the outset of treatment and addressed with targeted personalized interventions. Therapists may focus on increasing meaningful social interactions, addressing concerns related to treatment benefits, and creating a positive working relationship.

Objective To characterize nonpsychiatric prescription patterns of antidepressants according to drug labels and evidence assessments (on-label, evidence-based, and off-label) using structured outpatient electronic health record (EHR) data. Methods A retrospective analysis was conducted using deidentified EHR data from an outpatient practice at a New York City-based academic medical center. Structured “medication–diagnosis” pairs for antidepressants from 35 325 patients between January 2010 and December 2015 were compared to the latest drug product labels and evidence assessments. Results Of 140 929 antidepressant prescriptions prescribed by primary care providers (PCPs) and nonpsychiatry specialists, 69% were characterized as “on-label/evidence-based uses.” Depression diagnoses were associated with 67 233 (48%) prescriptions in this study, while pain diagnoses were slightly less common (35%). Manual chart review of “off-label use” prescriptions revealed that on-label/evidence-based diagnoses of depression (39%), anxiety (25%), insomnia (13%), mood disorders (7%), and neuropathic pain (5%) were frequently cited as prescription indication despite lacking ICD-9/10 documentation. Conclusions The results indicate that antidepressants may be prescribed for off-label uses, by PCPs and nonpsychiatry specialists, less frequently than believed. This study also points to the fact that there are a number of off-label uses that are efficacious and widely accepted by expert clinical opinion but have not been included in drug compendia. Despite the fact that diagnosis codes in the outpatient setting are notoriously inaccurate, our approach demonstrates that the correct codes are often documented in a patient’s recent diagnosis history. Examining both structured and unstructured data will help to further validate findings. Routinely collected clinical data in EHRs can serve as an important resource for future studies in investigating prescribing behaviors in outpatient clinics.