Anger Expression Styles, Cynical Hostility, and the Risk for the Development of Type 2 Diabetes or Diabetes-Related Heart Complications: Secondary Analysis of the Health and Retirement Study.

OBJECTIVE: Limited research has examined associations between trait anger and hostility and incident type 2 diabetes (T2D) and diabetes-related heart complications. However, anger expression styles (i.e., anger-in, anger-out) have not been examined. The present study used secondary data to examine the associations between anger expression styles, cynical hostility, and the risk of developing T2D (objective 1) or diabetes-related heart complications (objective 2). METHODS: Self-report data came from participants aged 50-75 in the Health and Retirement Study. Anger-in (anger that is suppressed and directed toward oneself), anger-out (anger directed towards other people or the environment), and cynical hostility were measured at baseline (i.e., 2006 or 2008). Follow-up data (i.e., diabetes status or diabetes-related heart complications status) were collected every two years thereafter until 2020. The objective 1 sample included 7,898 participants without T2D at baseline, whereas the objective 2 sample included 1,340 participants with T2D but without heart complications at baseline. RESULTS: Only anger-in was significantly associated with incident T2D after controlling for sociodemographic characteristics, HR = 1.08, 95% CI [1.01, 1.16], but the association did not hold after further adjustment for depressive symptoms. Only anger-out was significantly associated with incident diabetes-related heart complications after adjusting for sociodemographic characteristics, health-related covariates, and depressive symptoms, HR = 1.21, 95% CI [1.02, 1.39]. CONCLUSIONS: Anger expression styles were differentially related to diabetes outcomes. These findings demonstrate the value of expanding the operationalization of anger beyond trait anger in this literature and encourage further investigation of anger expression styles.

The longitudinal patterns of depression subtypes and stressors in depression severity in the Canadian longitudinal study on aging (CLSA).

AIM: The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID-19-related stressors, and depression severity. METHODS: The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long-term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID-19-related stressors, and depression severity among males and females, respectively. RESULTS: Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health-related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex-specific analyses also revealed differences in the associations between stressors and depression severity between males and females. CONCLUSIONS: This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic.

A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL.

First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412.

Manualized group cognitive behavioral therapy for social anxiety in first-episode psychosis: a randomized controlled trial.

BACKGROUND: Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the first episode of psychosis (FEP). For our primary outcome, we hypothesized that compared to the active control of group cognitive remediation (CR), the CBT-SA group would show a reduction in SA that would be maintained at 3- and 6-month follow-ups. For secondary outcomes, it was hypothesized that the CBT-SA group would show a reduction of positive and negative symptoms and improvements in recovery and functioning. METHOD: Ninety-six patients with an FEP and SA, recruited from five different FEP programs in the Montreal area, were randomized to 13 weekly group sessions of either CBT-SA or CR intervention. RESULTS: Linear mixed models revealed that multiple measures of SA significantly reduced over time, but with no significant group differences. Positive and negative symptoms, as well as functioning improved over time, with negative symptoms and functioning exhibiting a greater reduction in the CBT-SA group. CONCLUSIONS: While SA decreased over time with both interventions, a positive effect of the CBT-SA intervention on measures of negative symptoms, functioning, and self-reported recovery at follow-up suggests that our intervention had a positive effect that extended beyond symptoms specific to SA.ClinicalTrials.gov identifier: NCT02294409.

Prediabetes and the risk of type 2 diabetes: Investigating the roles of depressive and anxiety symptoms in the Lifelines cohort study.

AIMS: Depression and anxiety may increase the risk of progressing from prediabetes to type 2 diabetes. The present study examined the interactions between prediabetes status and elevated depressive and anxiety symptoms with the risk of type 2 diabetes. METHODS: Participants (N = 72,428) were adults aged 40 years and above without diabetes at baseline from the Lifelines Cohort Study (58% female; mean age = 51.4 years). The Mini-International Neuropsychiatric Interview screened for elevated symptoms of major depressive disorder and generalized anxiety disorder. Glycated haemoglobin A1c (HbA1c ) levels determined prediabetes status at baseline (2007-2013), and HbA1c and self-reported diabetes diagnoses determined diabetes status at follow-up (2014-2017). Groups were formed for elevated depressive and anxiety symptoms, respectively, and prediabetes status at baseline (elevated depressive/anxiety symptoms with prediabetes, elevated depressive/anxiety symptoms alone, and prediabetes alone), and compared to a reference group (no prediabetes or anxiety/depression) on the likelihood of developing diabetes during the follow-up period. RESULTS: N = 1300 (1.8%) participants developed diabetes. While prediabetes alone was associated with incident diabetes (OR = 5.94; 95% CI = 5.10-6.90, p < 0.001), the group with combined prediabetes and depressive symptoms had the highest likelihood of developing diabetes over follow-up (OR = 8.29; 95% CI = 5.58-12.32, p < 0.001). Similar results were found for prediabetes and anxiety symptoms (OR = 6.57; 95% CI = 4.62-9.33, p < 0.001), compared to prediabetes alone (OR = 6.09; 95% CI = 5.23-7.11, p < 0.001), though with a smaller effect. The interaction between depressive symptoms and prediabetes was synergistic in age-and-sex adjusted analyses. CONCLUSIONS: Individuals with elevated depressive, and to some extent anxiety, symptoms in combination with prediabetes may represent a high-risk subgroup for type 2 diabetes.

The role of ultra-processed food consumption and depression on type 2 diabetes incidence: a prospective community study in Quebec, Canada.

OBJECTIVES: The goal of the present study was to evaluate the association between depression and ultra-processed food (UPF) consumption as risk factors for developing type 2 diabetes (T2D). DESIGN: A prospective community study. SETTING: Baseline data (2009-2010) from CARTaGENE community health study from Quebec, Canada, were used. Food and drink consumption was assessed using the Canadian-Diet History Questionnaire II and grouped according to their degree of processing by the NOVA classification, and participants were categorised into tertiles of UPF (g/d). Depression was defined using either a validated cut-off score on the Patient Health Questionnaire-9 or antidepressant use. The outcome was the incidence of T2D, examined in 3880 participants by linking survey data with administrative health insurance data. Cox regression models estimated the associations between UPF, depression and incident T2D. PARTICIPANTS: 40-69-year-old individuals at baseline. RESULTS: In total, 263 (6·8 %) individuals developed T2D. Participants with high depressive symptoms and high UPF consumption showed the highest risk for T2D (adjusted hazard ratios (aHR) = 1·58, 95 % CI (0·98, 2·68)), compared to those with low depressive symptoms and low UPF consumption. The risk for T2D was similar when high depressive symptoms and antidepressant use were combined with high UPF (aHR 1·62, 95 % CI (1·02, 2·57)). CONCLUSIONS: This study shows that co-occurring depression and high UPF consumption were associated with a higher risk for T2D. Early management and monitoring of both risk factors might be essential for diabetes prevention.

Context and Expectations Matter: Social, Recreational, and Independent Functioning among Youth with Psychosis in Chennai, India and Montreal, Canada.

OBJECTIVES: Most cross-cultural psychosis research has focused on a limited number of outcomes (generally symptom-related) and perspectives (often clinician-/observer-rated). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to patient-reported measures of social, recreational, and independent functioning. Addressing this gap, this study aimed to compare these outcomes in first-episode psychosis at a high-income site and a lower middle-income site. METHODS: Patients receiving similarly designed early intervention for psychosis in Chennai, India (N = 164) and Montreal, Canada (N = 140) completed the self-reported Social Functioning Scale-Early Intervention, which measures prosocial, recreation, and independence-performance functioning. Their case managers rated expected independence-performance functioning. Both sets of assessments were done at entry and Months 6, 18, and 24. Linear mixed model analyses of differences between sites and over time were conducted, accounting for other pertinent variables, especially negative symptoms. RESULTS: Linear mixed models showed that prosocial, recreation, and independence-performance functioning scores were significantly higher in Montreal than Chennai and did not change over time. Expected independence-performance was also higher in Montreal and increased over time. Negative symptoms and education independently predicted prosocial, recreation, and expected independence-performance functioning. When added to the model, expected independence-performance predicted actual independence-performance and site was no longer significant. At both sites, prosocial and recreation scores were consistently lower (<40%) than independence-performance (40-65%). CONCLUSION: This is the first cross-cultural investigation of prosocial, recreation, and independent functioning in early psychosis. It demonstrates that these outcomes differ by socio-cultural context. Differing levels of expectations about patients, themselves shaped by cultural, illness, and social determinants, may contribute to cross-cultural variations in functional outcomes. At both sites, social, recreational, and independent functioning were in the low-to-moderate range and there was no improvement over time, underscoring the need for effective interventions specifically designed to impact these outcomes.

Trust of patients and families in mental healthcare providers and institutions: a cross-cultural study in Chennai, India, and Montreal, Canada.

PURPOSE: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada, and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. METHODS: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Nonparametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. RESULTS: The study included 333 patients (Montreal = 165, Chennai = 168) and 324 family members (Montreal = 128, Chennai = 168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. CONCLUSION: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Oral health-related quality of life and depressive symptoms in adults: longitudinal associations of the English Longitudinal Study of Ageing (ELSA).

BACKGROUND: Little is known about the relationship between oral health status and depressive symptoms in adults in England. The aim of this study was to examine the longitudinal association between oral health parameters and depressive symptoms in adults in England. METHODS: Data were obtained from the English Longitudinal Study of Aging (ELSA), which included information on self-rated oral health, oral impairment in daily life (Oral Impacts on Daily Performances, OIDP), and depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D) in 6790 adults aged ≥ 50 years. Wave 3 data were used as baseline, while Waves 5 and 7 were used for follow-up assessments. Logistic regression was used to determine whether depressive symptoms at baseline anticipated self-rated oral health and OIDP and whether oral health status (at baseline) was associated with the development of depressive symptoms at follow-up assessment. RESULTS: Participants with poor self-rated oral health were at higher risk of developing depressive symptoms, even after adjusting for behavioral, clinical, and sociodemographic characteristics (OR = 1.69, 95% CI 1.38-2.07). Similarly, having oral impacts on daily performances were associated with the development of depressive symptoms: The OR for developing depressive symptoms at Wave 5 or 7 was 2.19 (95% CI 1.62-2.96) after adjustment for all covariates. Participants with depressive symptoms at baseline were more likely to report poor self-rated oral health (OR = 1.93, 95% CI 1.52-2.44) or one or more oral impacts (OR = 1.86, 95% CI 1.45-2.40) at follow-up than those without depressive symptoms at baseline, even after adjusting for confounders. CONCLUSIONS: In the present study, a bidirectional association was found between depressive symptoms and poor oral health in older adults. Maintaining good oral health in older adults may be a protective factor against depressive symptoms. Therefore, more attention should be paid to promoting oral health awareness in older adults, including encouraging regular dental checkups, proper toothbrushing and flossing techniques, and healthy lifestyles.

International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI.

Great heterogeneity in survival exists for patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL). Three scoring systems incorporating simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We evaluated 2124 DLBCL patients treated from 1998 to 2009 with frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; or variant) across 7 multicenter randomized clinical trials to determine which scoring system best discriminates overall survival (OS). Median age was 63 years, and 56% of patients were male. Five-year OS estimates ranged from 54% to 88%, from 61% to 93%, and from 49% to 92% using the IPI, R-IPI, and NCCN-IPI, respectively. The NCCN-IPI had the greatest absolute difference in OS estimates between the highest- and lowest-risk groups and best discriminated OS (concordance index = 0.632 vs 0.626 [IPI] vs 0.590 [R-IPI]). For each given IPI risk category, NCCN-IPI risk categories were significantly associated with OS (P ≤ .01); the reverse was not true, and the IPI did not provide additional significant prognostic information within all NCCN-IPI risk categories. Collectively, the NCCN-IPI outperformed the IPI and R-IPI. Patients with low-risk NCCN-IPI had favorable survival outcomes with little room for further improvement. In the rituximab era, none of the clinical risk scores identified a patient subgroup with long-term survival clearly <50%. Integrating molecular features of the tumor and microenvironment into the NCCN-IPI or IPI might better characterize a high-risk group for which novel treatment approaches are most needed.

Does providing personalized depression risk information lead to increased psychological distress and functional impairment? Results from a mixed-methods randomized controlled trial.

BACKGROUND: Multivariable risk algorithms (MVRP) predicting the personal risk of depression will form an important component of personalized preventive interventions. However, it is unknown whether providing personalized depression risk will lead to unintended psychological harms. The objectives of this study were to evaluate the impact of providing personalized depression risk on non-specific psychological distress and functional impairment over 12 months. METHODS: A mixed-methods randomized controlled trial was conducted in 358 males and 354 females who were at high risk of having a major depressive episode according to sex-specific MVRPs, and who were randomly recruited across Canada. Participants were assessed at baseline, 6 and 12 months. RESULTS: Over 93% of participants were interested in knowing their depression risk. The intervention group had a greater reduction in K10 score over 12 months than the control group; complete-case analysis found a significant between-group difference in mean K10 change score (d = 1.17, 95% CI 0.12-2.23) at 12 months. Participants in the intervention group also reported significantly less functional impairment in the domains of home and work/school activities, than did those in the control group. A majority of the qualitative interviewees commented that personalized depression risk information does not have a negative impact on physical and mental health. CONCLUSIONS: This study found no evidence that providing personalized depression risk information will lead to worsening psychological distress, functional impairment, and absenteeism. Provision of personalized depression risk information may have positive impacts on non-specific psychological distress and functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT02943876.

Context and contact: a comparison of patient and family engagement with early intervention services for psychosis in India and Canada.

BACKGROUND: It is unknown whether patient disengagement from early intervention services for psychosis is as prevalent in low- and middle-income countries (LMICs) like India, as it is in high-income countries (HICs). Addressing this gap, we studied two first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized lower service disengagement among patients and higher engagement among families in Chennai, and that family engagement would mediate cross-site differences in patient disengagement. METHODS: Sites were compared on their 2-year patient disengagement and family engagement rates conducting time-to-event analyses and independent samples t tests on monthly contact data. Along with site and family involvement, Cox proportional hazards regression included known predictors of patient disengagement (e.g. gender). RESULTS: The study included data about 333 patients (165 in Montreal, 168 in Chennai) and their family members (156 in Montreal, 168 in Chennai). More Montreal patients (19%) disengaged before 24 months than Chennai patients (1%), χ2(1, N = 333) = 28.87, p < 0.001. Chennai families had more contact with clinicians throughout treatment (Cohen's d = -1.28). Family contact significantly predicted patient disengagement in Montreal (HR = 0.87, 95% CI 0.81-0.93). Unlike in Chennai, family contact declined over time in Montreal, with clinicians perceiving such contact as not necessary (Cohen's d = 1.73). CONCLUSIONS: This is the first investigation of early psychosis service engagement across a HIC and an LMIC. Patient and family engagement was strikingly higher in Chennai. Maintaining family contact may benefit patient engagement, irrespective of context. Findings also suggest that differential service utilization may underpin cross-cultural variations in psychosis outcomes.

Trajectories of Depressive Symptoms and Incident Diabetes: A Prospective Study.

BACKGROUND: Elevated depressive symptoms are associated with an increased risk for diabetes. Depression is a heterogeneous and chronic condition in which symptoms may remit, emerge, lessen, or intensify over time. PURPOSE: The purpose of this study was to determine if trajectories of depressive symptoms measured at five time points over 8 years predicted incident diabetes over an 8-year follow-up in middle-aged and older adults. A secondary aim was to determine if trajectories of depressive symptoms predict incident diabetes, above and beyond depressive symptoms measured at a single time point. METHODS: Data came from the Health and Retirement Study (n = 9,233). Depressive symptoms were measured biennially from 1998 to 2006. Self-reported incident diabetes was measured during an 8-year follow-up. RESULTS: Five trajectories of depressive symptoms were identified (no depressive symptoms, low depressive symptoms, low-moderate depressive symptoms, moderate depressive symptoms, elevated and increasing depressive symptoms). Compared to the no depressive symptoms trajectory group (referent), all other trajectory groups were at higher risk of developing diabetes after adjusting for covariates. In most cases, trajectory group membership was associated with incident diabetes after controlling for depressive symptoms at a single time point. CONCLUSIONS: Patterns of depressive symptoms over time were associated with incident diabetes. Patterns of depressive symptoms may be more predictive of diabetes incidence than depressive symptoms measured at a single time point.

Unfinished business: Functional outcomes in a randomized controlled trial of a three-year extension of early intervention versus regular care following two years of early intervention for psychosis.

OBJECTIVE: To investigate whether first-episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes. METHODS: This is a randomized controlled single-blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3-year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well-known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3-year period. RESULTS: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying. CONCLUSION: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one-third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high-school completion may be additional avenues for targeting functional recovery.

Adverse childhood experiences and cognitive function in adulthood: examining the roles of depressive symptoms and inflammation in a prospective cohort study.

PURPOSE: Adverse childhood experiences (ACEs) have been associated with cognitive decline in adulthood. However, the underlying mechanisms implicated remain unclear. This study investigated depressive symptoms and systemic inflammation as potential mediators of the association between ACEs and later cognitive function. METHODS: Participants were adults aged 50 + from the English Longitudinal Study of Ageing (N = 3029; 54.8% female). Measures included self-reported ACEs at wave 3 (2006-2007), C-reactive protein (CRP) and depressive symptoms at wave 4 (2008-2009), and cognitive function at waves 3 and 7 (2014-2015). Mediation analyses examined the direct associations between ACEs and cognitive function at wave 7 and the indirect associations via depressive symptoms and CRP at wave 4. In a first set of analyses, models were adjusted for sociodemographic factors and baseline cognitive function. In a second set of analyses, models were additionally adjusted for BMI and health behaviours (n = 1915). RESULTS: Cumulative ACEs exposure positively predicted depressive symptoms (b = 0.184, s.e. = 0.034, p < .001), which in turn predicted poorer cognitive function at wave 7 (b = - 0.035, s.e. = 0.008, p < .001). ACEs also positively predicted systemic inflammation as measured by CRP (b = 0.031, s.e. = 0.01, p = 0.0016). However, CRP did not mediate the association between ACEs and later cognitive function (b = - 0.0002, 95% CI: - 0.002, 0.002). CONCLUSION: These findings suggest that ACEs may be related to cognitive decline partly via depressive symptoms and corroborate prior research linking ACEs with systemic inflammation in adulthood.

An observational study of antipsychotic medication discontinuation in first-episode psychosis: clinical and functional outcomes.

PURPOSE: To study the impact of supervised antipsychotic medication discontinuation on clinical and functional outcomes in first-episode psychosis (FEP) in two different cultural environments. METHOD: FEP patients(N = 253), treated in two early intervention services (Montreal, Canada and Chennai, India) for 2 years, were assessed for medication use, positive and negative symptom remission and social-occupational functioning at regular intervals. RESULTS: Between months 4 and 24 of treatment, 107 patients discontinued medication ('Off'group) as compared to 146 who stayed on medication ('On'group). Medication discontinuation was higher in Chennai as compared to Montreal (n = 80, 49.07% vs n = 27, 16.87%; χ2 37.80, p < 0.001), with no difference in time to discontinuation [Means(SDs) = 10.64(6.82) and 10.04(5.43), respectively, p = 0.71). At month 24 (N = 235), there were no differences in the rate of positive symptom remission between the on and Off groups (81.5 vs 88.0%, respectively) at both sites. The rate of negative symptom remission was lower among patients in the On compared to the Off group (63.2 vs 87.9%, respectively, χ2 = 17.91, p < 0.001), but only in Montreal (55.4% vs 80.0%, respectively, χ2 = 4.12, p < 0.05). Social and Occupational Functioning Assessment Scale scores were equally high in both Off and On medication groups in Chennai [Means (SDs) = 79.43(12.95) and 73.59(17.63), respectively] but higher in the Off compared to the On group in Montreal Means (SDs) = 77.47(14.97) and 64.94(19.02), respectively; Time × site interaction F = 3.96(1,217), p < 0.05]. Medication status (On-Off) had no impact on the outcomes, independent of other variables known to influence outcomes. CONCLUSION: Certain cultural environments and patient characteristics may facilitate supervised discontinuation of antipsychotic medication following treatment of an FEP without negative consequences.

The impact of hospital-diagnosed depression or use of antidepressants on treatment initiation, adherence and HbA1c/LDL target achievement in newly diagnosed type 2 diabetes.

AIMS/HYPOTHESIS: We aimed to assess whether current antidepressant therapy or a history of hospital-diagnosed depression affects diabetes treatment initiation, adherence, and HbA1c and LDL-cholesterol target achievement. METHODS: In this register-based study, we included all individuals from Central and Northern Denmark with newly diagnosed type 2 diabetes, defined as a first-ever HbA1c measurement of ≥48 mmol/mol (6.5%), between 2000 and 2016. Individuals either diagnosed with depression at a psychiatric hospital in the 2 years prior to their diabetes diagnosis or currently receiving treatment with an antidepressant were compared with individuals with type 2 diabetes, but without depression treatment or previous history of depression. Outcome measures included initiation of glucose-lowering drugs and lipid-modifying agents, adherence to these medications (medication possession ratio >80%), and HbA1c (<53 mmol/mol [7%]) and LDL-cholesterol (<2.6 mmol/l) target achievement. The assessment of association between depression or antidepressant treatment and these outcomes was conducted using regression analyses with adjustment for potential confounders. RESULTS: We included a total of 87,650 individuals with first-ever HbA1c-diagnosed type 2 diabetes, of whom 0.9% (n = 784) had hospital-diagnosed depression and 11.4% (n = 9963) currently received antidepressant treatment. Compared with those without depression treatment, treatment with an antidepressant was associated with increased likelihood of glucose-lowering drug initiation (HR 1.39 [95% CI 1.34, 1.44]) and adherence (OR 1.27 [95% CI 1.18, 1.36]), lipid-modifying agent initiation (HR 1.17 [95% CI 1.11, 1.23]) and adherence (OR 1.25 [95% CI 1.09, 1.43]), and achievement of LDL (OR 1.08 [95% CI 1.03, 1.14]) but not HbA1c target (OR 0.99 [95% CI 0.93, 1.06]). The findings were similar for individuals who had hospital-diagnosed depression. CONCLUSIONS/INTERPRETATION: In individuals with newly diagnosed type 2 diabetes, antidepressant treatment and depression were associated with improved diabetes treatment quality. Graphical abstract.

The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis.

Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0-163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.

Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma-data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin's Lymphoma Study Group).

In elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61-65 years, 66-70 years, 71-75 years, and 76-80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76-80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

Relapsed/Refractory International Prognostic Index (R/R-IPI): An international prognostic calculator for relapsed/refractory diffuse large B-cell lymphoma.

Disease progression after frontline therapy for Diffuse large B-cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time-dependent concordance indices (c-statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post-progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post-progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR-T therapy as well as trial designs. The model is available in smartphone-based point of care applications.