Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features.

Some data suggest that antipsychotics may adversely affect brain structure. We examined the relationship among olanzapine exposure, relapse, and changes in brain structure in patients with major depressive disorder with psychotic features. We analyzed data from the Study of the Pharmacotherapy of Psychotic Depression II trial (STOP-PD II), a randomized, placebo-controlled trial in patients with psychotic depression who attained remission on sertraline and olanzapine and were randomized to continue sertraline plus olanzapine or placebo for 36 weeks. Olanzapine steady state concentration (SSC) were calculated based on sparsely-sampled levels. Rates of relapse and changes in brain structure were assessed as outcomes. There were significant associations between dosage and relapse rates (N = 118; HR = 0.94, 95% CI [0.897, 0.977], p = 0.002) or changes in left cortical thickness (N = 44; B = -2.0 × 10-3, 95% CI [-3.1 × 10-3, -9.6 × 10-4], p < 0.001) and between SSC and changes in left cortical thickness (N = 44; B = -8.7 × 10-4, 95% CI [-1.4 × 10-3, -3.6 × 10-4], p = 0.001). Similar results were found for the right cortex. These associations were no longer significant when the analysis was restricted to participants treated with olanzapine. Our findings suggest that, within its therapeutic range, the effect of olanzapine on relapse or cortical thickness does not depend on its dosage or SSC. Further research is needed on the effect of olanzapine and other antipsychotics on mood symptoms and brain structure.

Consenting rather than choosing. A qualitative study on overseas patients' decision to undergo hematopoietic stem cell transplantation.

OBJECTIVE: Reasons for patients' acceptance of the allogeneic hematopoietic stem cell transplantation (allo-HSCT) proposed and how their decision may be affected by the long distances involved have not been sufficiently investigated so far. We therefore conducted a qualitative study to identify the factors involved in overseas patients' decision to accept allo-HSCT. METHODS: In-depth semi-directive interviews were conducted with overseas allo-grafted patients (n = 22), as well as one non-consenting patient and their caregivers (n = 24). Interviews were analyzed taking an inductive thematic approach. RESULTS: Respondents stated that their decision to undergo the transplantation was constrained by their feeling of being in a therapeutic impasse, the need for a survival strategy, the need to survive for their family's sake, family and doctors' pressures, and the feeling of being managed. The following factors favoring patients' acceptance were the medical information received, their faith, having a family donor, peer testimonies, and positive representations of the transplantation. Factors against patients' acceptance were geographical distance from home to the transplant center, apprehension of protective isolation, fear of dying, and representations of the graft. CONCLUSIONS: These factors, such as patient's personal values and representations, need to be weighed up in order to adapt the information exchanged accordingly. Efforts are required to relieve patients' social isolation and improve the means of providing family support.

[Cost of high-throughput sequencing (NGS) technologies: Literature review and insights]. / Coût des technologies de séquençage haut débit (NGS) : revue de la littérature et enseignements.

Although high-throughput sequencing technologies (Next-Generation Sequencing [NGS]) are revolutionizing medicine, the estimation of their production cost for pricing/tariffication by health systems raises methodological questions. The objective of this review of cost studies of high-throughput sequencing techniques is to draw lessons for producing robust cost estimates of these techniques. We analyzed, using an eleven item analysis framework, micro-costing studies of high-throughput sequencing technologies (n=17), including two studies conducted in the French context. The factors of variability between the studies that we identified were temporality (early evaluation of the innovation vs. evaluation of a mature technology), the choice of cost evaluation method (scope, micro- vs. gross-costing technique), the choice of production steps observed and the transposability of these studies. The lessons we have learned are that it is necessary to have a comprehensive vision of the sequencing production process by integrating all the steps from the collection of the biological sample to the delivery of the result to the clinician. It is also important to distinguish between what refers to the local context and what refers to the general context, by favouring the use of mixed methods to calculate costs. Finally, sensitivity analyses and periodic re-estimation of the costs of the techniques must be carried out in order to be able to revise the tariffs according to changes linked to the diffusion of the technology and to competition between reagent suppliers.

Trajectories of remitted psychotic depression: identification of predictors of worsening by machine learning.

BACKGROUND: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory. METHOD: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics. RESULTS: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model. CONCLUSIONS: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Hypoparathyroidism-related health care utilization and expenditure during the first postoperative year after total thyroidectomy for cancer: a comprehensive national cohort study.

Objectives: Hypoparathyroidism is the most common complication of total thyroidectomy for cancer, and requires calcium and/or vitamin D supplementation for an unpredictable period of time. The additional cost associated with this complication has not hitherto been assessed. The aim of this study was to assess the economic burden of postoperative hypoparathyroidism after total thyroidectomy for cancer in France. Methods: Based on the French national cancer cohort, which extracts data from the French National Health Data System (SNDS), all adult patients who underwent a total thyroidectomy for cancer in France between 2011 and 2015 were identified, and their healthcare resource use during the first postoperative year was compared according to whether they were treated postoperatively with calcium and/or vitamin D or not. Univariate and multivariate cost analyses were performed with the non-parametric Wilcoxon test and generalized linear model (gamma distribution and log link), respectively. Results: Among the 31,175 patients analyzed (75% female, median age: 52y), 13,247 (42%) started calcium and/or vitamin D supplementation within the first postoperative month, and 2,855 patients (9.1%) were still treated at 1 year. Over the first postoperative year, mean overall and specific health expenditures were significantly higher for treated patients than for untreated patients: €7,233 vs €6,934 per patient (p<0.0001) and €478.6 vs €332.7 per patient (p<0.0001), respectively. After adjusting for age, gender, Charlson Comorbidity index, ecological deprivation index, types of thyroid resection, lymph node dissection and complications, year and region, the incremental cost of overall health care utilization was €142 (p<0.004). Conclusion: Our study found a significant additional cost in respect of health expenditures for patients who had hypoparathyroidism after thyroidectomy for cancer, over the first postoperative year. Five-year follow-up is planned to assess the impact of more severe long-term complications on costs.

A non-inferiority randomized phase III trial of standard immunotherapy by checkpoint inhibitors vs. reduced dose intensity in responding patients with metastatic cancer: the MOIO protocol study.

BACKGROUND: Immunotherapy (IO) has become a standard of care for treating various types of metastatic cancers and has significantly improved clinical outcome. With the exception of metastatic melanoma in complete response for which treatment can be stopped at 6 months, these treatments are currently administered until either disease progression for some IO, 2 years for others, or unacceptable toxicity. However, a growing number of studies are reporting maintenance of response despite discontinuation of therapy. There is currently no evidence of a dose effect of IO in pharmacokinetic studies. Maintaining efficacy despite a reduction in treatment intensity by decreasing the frequency of administration in patients with highly selected metastatic cancer, is the hypothesis evaluated in the MOIO study. METHOD/DESIGN: This non-inferiority, randomized phase III study aims to compare the standard regimen to a 3 monthly regimen of variousIO drugs in adult patients with metastatic cancer in partial (PR) or complete response (CR) after 6 months of standard IO dosing (except melanoma in CR). This is a French national study conducted in 36 centers. The main objective is to demonstrate that the efficacy of a three-monthly administration is not unacceptably less efficacious than a standard administration. Secondary objectives are cost-effectiveness, quality of life (QOL), anxiety, fear of relapse, response rate, overall survival and toxicity. After 6 months of standard IO, patients with partial or complete response will be randomized 1:1 between standard IO or a reduced intensity dose of IO, administered every 3 months. The randomization will be stratified on therapy line,, tumor type, IO type and response status. The primary endpoint is the hazard ratio of progression-free survival. With a planned study duration of 6 years, including 36 months enrolment time, 646 patients are planned to demonstrate with a statistical level of evidence of 5% that the reduced IO regimen is non-inferior to the standard IO regimen, with a relative non-inferiority margin set at 1.3. DISCUSSION: Should the hypothesis of non-inferiority with an IO reduced dose intensity be validated, alternate scheduling could preserve efficacy while being cost-effective and allowing a reduction of the toxicity, with an increase in patient's QOL. TRIAL REGISTRATION: NCT05078047.

The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression.

BACKGROUND: Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. METHODS: We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. RESULTS: CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. LIMITATIONS: As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. CONCLUSIONS: While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. CLINICAL TRIAL REGISTRATION: Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608.

Effects of antipsychotic medication on functional connectivity in major depressive disorder with psychotic features.

The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain.

Genomic Investigation of Remission and Relapse of Psychotic Depression Treated with Sertraline plus Olanzapine: The STOP-PD II Study.

INTRODUCTION: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. METHODS: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. RESULTS: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse. CONCLUSION: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.

Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database.

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

Residual or re-emergent impaired insight into delusions following remission is unrelated to later relapse during a randomized clinical trial of continuation pharmacotherapy for psychotic depression - The STOP-PD II Study.

BACKGROUND: Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined. METHODS: Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment. RESULTS: Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse. LIMITATIONS: Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse. CONCLUSION: Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial.

Predictors of relapse of psychotic depression: Findings from the STOP-PD II randomized clinical trial.

Psychotic depression has a high rate of relapse. The study aims were to identify a prediction model of risk of relapse of psychotic depression and examine whether predictors moderated the effect of treatment on relapse. One hundred and twenty-six men and women aged 18-85 years, who experienced sustained remission or near-remission of psychotic depression with sertraline plus olanzapine, participated in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse (NCT01427608). Cox regression analyses were performed to identify significant predictors of relapse and to model the combined role of significant predictors. Concordance statistic was calculated to determine the accuracy of the best fit multivariable models in predicting relapse. Finally, interaction terms were tested for each significant predictor to examine whether they moderated the effect of treatment on risk of relapse. Lifetime number of depressive episodes, severity of residual depressive symptoms at the time of randomization, and psychomotor disturbance both at acute enrollment when participants were depressed and at the time of randomization predicted risk of relapse. Multivariable models had 69-70% accuracy in predicting relapse. Psychomotor disturbance was associated with increased risk of relapse in the sertraline plus olanzapine group compared with sertraline plus placebo, whereas the other predictors did not moderate the effect of treatment on relapse. Future research is needed to determine whether a combination of clinical and biological variables can further increase the accuracy of prediction of relapse of psychotic depression.

Placebo Effect in Randomized Trials of Major Depressive Disorder With Psychotic Features: A Systematic Review and Descriptive Meta-Analysis.

BACKGROUND: In the 1980s, the response rate of major depressive disorder with psychotic features (MDD-Psy) to placebo pills was reported to be close to 0%. To our knowledge, this placebo response rate has not been systematically reassessed. We undertook a systematic review of randomized controlled trials (RCTs) that have used a placebo or sham control group for MDD-Psy. METHODS: We searched MEDLINE and identified 9 relevant publications reporting on 10 studies comparing a placebo or sham interventions versus an active intervention. We extracted reported rates of response or of dropout for all causes associated with placebo versus active intervention(s) and aggregated response and dropout rates across trials. RESULTS: Two sham-controlled electroconvulsive therapy (ECT) trials did not provide response rates. In the 3 pharmacotherapy studies published in the 1980s, 0 of 12 participants (0%) responded to placebo versus 13 of 38 (34.2%) responding to the active interventions. In contrast, 5 RCTs published in the 2000s, 114 of 339 participants (33.6%) randomized to placebo responded versus 149 of 373 participants (39.9%) randomized to active interventions; dropout rates were 71/236 (30.1%) for placebo versus 84/282 (29.8%) for the active interventions. CONCLUSIONS: As expected, response rates to placebo pills in RCTs for MDD-Psy increased markedly from the 1980s to the 2000s. Methodological issues in the design and conduct of more recent RCTs may have contributed to the high placebo response. However, one needs to consider this placebo response rate when interpreting the result of recent trials of MDD-Psy, which typically have not included a "pure" placebo condition.

Impact of active surveillance for prostate cancer on the risk of depression and anxiety.

Active surveillance (AS) is a standard treatment option for low risk localized prostate cancer. However, the risk of anxiety and depression compared to other curative strategies, namely radical prostatectomy (RP) and radiotherapy (RT), is controversial. This study consisted in a French representative sample of 4174 5-years cancer survivors. Self-reported data, including quality-of-life assessment, were prospectively collected through telephone interviews. Among the 447 survivors with PC, we selected 292 patients with localized prostate cancer, T1-T2 stage, Gleason score ≤ 7 and we compared anxiety and depressive symptoms according to treatment strategy. Among patients on AS, 14.9% received curative treatment during the 5 years of follow-up. Anxiety was reported in 34.3% of cases in the AS group versus 28.6% in the RP group and 31.6% in the RT group (p = 0.400), while depressive symptoms were reported in 14.9% of cases in the AS group versus 10.7% in the RP group and 22.8% in the RT group (p = 0.770). Consumption of anxiolytics reported did not vary significantly between the 3 groups (p = 0.330). In conclusion, patients managed with AS for localized prostate cancer do not report more anxiety or depressive symptoms than patients managed with curative treatment, encouraging the extended use of active surveillance.

Factor analysis of the CORE measure of psychomotor disturbance in psychotic depression: Findings from the STOP-PD II study.

The CORE instrument is commonly used to measure psychomotor disturbance. We examined the factor structure of the CORE in 266 adults with an acute episode psychotic depression, a disorder with a high rate of psychomotor disturbance. Exploratory factor analysis identified a two-factor solution: Factor 1 corresponded to the CORE's retardation and non-interactiveness items and Factor 2 corresponded to its agitation items. Internal consistency was excellent for Factor 1 but questionable for Factor 2. These findings suggest that the CORE's retardation and non-interactiveness items should be combined in one subscale when assessing patients with an acute episode of psychotic depression.

The Psychological Distress of Cancer Patients following the COVID-19 Pandemic First Lockdown: Results from a Large French Survey.

Cancer patients commonly experience psychological distress that may increase with the current COVID-19 pandemic. This prospective study aimed to measure post-traumatic stress disorder (PTSD) and anxiety in cancer patients following France's first COVID-19-related lockdown, together with associated factors. Cancer patients receiving outpatient treatment or post-treatment follow-up completed a questionnaire which measured, among other things, PTSD (IES-R), anxiety (State-Trait Anxiety Inventory), and fear of cancer recurrence (FCR). Of the 1097 patients included in the study, 14.7% and 30.5% suffered from PTSD and anxiety, respectively. Patients afraid to come to hospital due to the risk of COVID-19 transmission (OR = 3.49, p < 0.001), those with a negative lockdown experience (OR = 0.98, p < 0.001), women (OR = 1.97; p = 0.009), and patients living alone (OR = 1.63, p = 0.045) were all more likely to have PTSD. Older patients (OR = 1.65, p = 0.020), women (OR = 1.62, p = 0.018), those with a higher FCR score (OR = 5.02, p < 0.001), patients unsatisfied with their cancer management (OR = 2.36, p < 0.001), and those afraid to come to hospital due to COVID-19 (OR = 2.43, p < 0.001) all had a higher risk of anxiety. These results provide a greater understanding of the psychological consequences of the COVID-19 pandemic in cancer patients and highlight the need to better integrate psychosocial support in pandemic response measures in order to guide health systems.

Lived experience of State-sponsored intra-national overseas therapeutic mobility for stem cell transplantation.

This article focuses on the lived experience of patients with haematological cancer who were transferred from La Réunion (a French overseas Department) to mainland France to undergo allogeneic haematopoietic stem cell transplantation (allo-HSCT). Based on a qualitative study conducted between February 2020 and January 2021 with allo-HSCT recipients, their family caregivers and healthcare professionals, we examined the social, economic and cultural factors shaping the patients' complex experience. We have called this kind of State-sponsored intra-national medical transfer "overseas therapeutic mobility". The patients' experience of this therapeutic journey beyond their geographical and cultural frontiers has some similarities with transnational therapeutic mobility. Overseas therapeutic mobility to undergo highly technical treatment requires considerable logistic efforts and mobility skills. The remoteness of their families and their affective and cultural environment give mobile patients a feeling of disorientation and causes them much social suffering. The two-fold condition of being a sick person with a possibly lethal disease and being treated overseas can be regarded as a double ordeal. In addition, the unfunded costs place a heavy burden on the patients and those whose families have limited resources. This study points to the cleavages which occur between post-colonial overseas regions and mainland France, and the territorial inequalities existing in patients' access to specialized treatment due to French policies of healthcare centralization.

Self-reported functional assessment after treatment for prostate cancer: 5-year results of the prospective cohort VICAN.

Objective: We aimed to assess the long-term association of therapeutic strategies with urinary, sexual function and health-related quality of life (HR-QoL) for 5-year prostate cancer (PC) survivors. Materials & methods: The VICAN survey consisted of self-reported data prospectively collected, including living conditions, treatment side effects and quality of life (QoL) of cancer survivors. Results: Among the 434 PC survivors, 52.8% reported urinary incontinence (UI) and 55.8% reported erectile dysfunction (ED). Patients treated with radical prostatectomy with salvage radiotherapy reported significantly more UI (p = 0.014) and more ED (p = 0.012) compared with other strategies. UI was significantly associated with physical and mental health-related QoL (p = 0.045 and p = 0.049, respectively). Conclusion: Self-assessed functional outcomes 5 years after PC diagnosis remain poor and could have an impact on health-related QoL.

Patients treated for prostate cancer may have long-term consequences due to the treatment they receive ­ in particular urinary incontinence (UI) and erectile dysfunction (ED). We analyzed self-reported data from 434 patients diagnosed with prostate cancer 5 years earlier, focusing especially on treatment side effects and the impact on patient quality of life. Of these patients, 52.8% reported UI and 55.8% reported ED. Patients treated with surgery plus radiotherapy reported significantly more UI and more ED compared with other treatment strategies. We have also shown that UI has an impact on physical and mental quality of life of these patients. In conclusion, functional recovery 5 years after prostate cancer diagnosis remains poor and requires implementation of new, long-term management strategies for cancer survivors.

Modifiable predictors of suicidal ideation during psychotherapy for late-life major depression. A machine learning approach.

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.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. RESULTS: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. CONCLUSION: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.