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ImportanceApproximately half of older adults with depression remain symptomatic at treatment end. Identifying discrete clinical profiles associated with treatment outcomes may guide development of personalized psychosocial interventions.ObjectiveTo identify clinical subtypes of late-life depression and examine their depression trajectory during psychosocial interventions in older adults with depression.Design, Setting, and ParticipantsThis prognostic study included older adults aged 60 years or older who had major depression and participated in 1 of 4 randomized clinical trials of psychosocial interventions for late-life depression. Participants were recruited from the community and outpatient services of Weill Cornell Medicine and the University of California, San Francisco, between March 2002 and April 2013. Data were analyzed from February 2019 to February 2023.InterventionsParticipants received 8 to 14 sessions of (1) personalized intervention for patients with major depression and chronic obstructive pulmonary disease, (2) problem-solving therapy, (3) supportive therapy, or (4) active comparison conditions (treatment as usual or case management).Main Outcomes and MeasuresThe main outcome was the trajectory of depression severity, assessed using the Hamilton Depression Rating Scale (HAM-D). A data-driven, unsupervised, hierarchical clustering of HAM-D items at baseline was conducted to detect clusters of depressive symptoms. A bipartite network analysis was used to identify clinical subtypes at baseline, accounting for both between- and within-patient variability across domains of psychopathology, social support, cognitive impairment, and disability. The trajectories of depression severity in the identified subtypes were compared using mixed-effects models, and time to remission (HAM-D score ≤10) was compared using survival analysis.ResultsThe bipartite network analysis, which included 535 older adults with major depression (mean [SD] age, 72.7 [8.7] years; 70.7% female), identified 3 clinical subtypes: (1) individuals with severe depression and a large social network; (2) older, educated individuals experiencing strong social support and social interactions; and (3) individuals with disability. There was a significant difference in depression trajectories (F2,2976.9 = 9.4; P 22 = 18.2; P Conclusions and RelevanceIn this prognostic study, bipartite network clustering identified 3 subtypes of late-life depression. Knowledge of patients’ clinical characteristics may inform treatment selection. Identification of discrete subtypes of late-life depression may stimulate the development of novel, streamlined interventions targeting the clinical vulnerabilities of each subtype.

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.

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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.

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.

We examined long-term risks and predictors of mesh erosion and reoperation following mid urethral sling procedure for stress urinary incontinence.Women aged 18 years or older who received a mid urethral sling for stress urinary incontinence between 2008 and 2016 in outpatient surgical settings in New York State were included in our study. Those who underwent concomitant mesh pelvic organ prolapse repair were excluded. Primary outcomes were post-implantation time to erosion and reoperations. Kaplan-Meier analysis and Cox proportional hazard models were used to assess the risks of erosion diagnosis and reoperation.Our cohort included 36,195 women with a mean±SD age of 53.7±12.4 years. Estimated risks of erosions and reoperations at 7 years after sling procedures were 3.7% and 6.7%, respectively. Older age (≥65 vs65: HR 0.83, 95% CI 0.70-0.99) and high volume facilities (high vs low: HR 0.79, 95% CI 0.68-0.92) were associated with a lower risk of erosion. History of hysterectomy was associated with a higher risk of erosion (HR 1.62, 95% CI 1.36-1.92). Predictors of reoperation included concurrent abdominal or native tissue transvaginal prolapse repair, previous hysterectomy and depression.One in 27 women had sling erosions and 1 in 15 had invasive reoperations at 7 years after sling procedures. The highest erosion cases were observed among younger White women treated at low volume facilities. Continued and vigilant surveillance of mesh in stress urinary incontinence repairs, the nature and burden of stress urinary incontinence recurrence, different types of re-treatment, patient reported outcomes and information about treating surgeons are crucial.

To examine the association between baseline glucose control and risk of COVID-19 hospitalization and in-hospital death among patients with diabetes.We performed a retrospective cohort study of adult patients in the INSIGHT Clinical Research Network with a diabetes diagnosis and haemoglobin A1c (HbA1c) measurement in the year prior to an index date of March 15, 2020. Patients were divided into four exposure groups based on their most recent HbA1c measurement (in mmol/mol): 39-46 (5.7%-6.4%), 48-57 (6.5%-7.4%), 58-85 (7.5%-9.9%), and ≥86 (10%). Time to COVID-19 hospitalization was compared in the four groups in a propensity score-weighted Cox proportional hazards model adjusting for potential confounders. Patients were followed until June 15, 2020. In-hospital death was examined as a secondary outcome.Of 168,803 patients who met inclusion criteria; 50,016 patients had baseline HbA1c 39-46 (5.7%-6.4%); 54,729 had HbA1c 48-57 (6.5-7.4%); 47,640 had HbA1c 58-85 (7.5^%-9.9%) and 16,418 had HbA1c ≥86 (10%). Compared with patients with HbA1c 48-57 (6.5%-7.4%), the risk of hospitalization was incrementally greater for those with HbA1c 58-85 (7.5%-9.9%) (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 1.06-1.34) and HbA1c ≥86 (10%) (aHR 1.40, 95% CI 1.19-1.64). The risk of COVID-19 in-hospital death was increased only in patients with HbA1c 58-85 (7.5%-9.9%) (aHR 1.29, 95% CI 1.06, 1.61).Diabetes patients with high baseline HbA1c had a greater risk of COVID-19 hospitalization, although association between HbA1c and in-hospital death was less consistent. Preventive efforts for COVID-19 should be focused on diabetes patients with poor glucose control.

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.