Excess mortality and its causes among older adults with schizophrenia versus those with bipolar disorder and major depressive disorder: a 5-year prospective multicenter study.

Excess mortality observed in people with schizophrenia may persist in later life. The specific causes of increased mortality observed in older adults with schizophrenia and the potential influence of psychotropic medications remain partly unknown. We compared 5-year mortality and its causes of older adults with schizophrenia to bipolar disorder (BD) or major depressive disorder (MDD). We used a 5-year prospective cohort, including 564 older inpatients and outpatients with schizophrenia, BD or MDD (mean age: 67.9 years, SD = 7.2 years). Causes of death were cardiovascular disorder (CVD) mortality, non-CVD disease-related mortality (e.g., infections), suicide, and unintentional injury. The primary analysis was a multivariable logistic model with inverse probability weighting (IPW) to reduce the effects of confounders, including sociodemographic factors, duration and severity of the disorder, and psychiatric and non-psychiatric comorbidity. Five-year all-cause mortality among older participants with schizophrenia and with BD or MDD were 29.4% (n = 89) and 18.4% (n = 45), respectively. Following adjustments, schizophrenia compared to MDD or BD was significantly associated with increased all-cause mortality (AOR = 1.35; 95%CI = 1.04-1.76; p = 0.024) and cardiovascular mortality (AOR = 1.50; 95%CI = 1.13-1.99; p = 0.005). These associations were significantly reduced among patients taking antidepressants [interaction odds ratio (IOR) = 0.42; 95%CI = 0.22-0.79; p = 0.008 and IOR = 0.39: 95%CI = 0.16-0.94; p = 0.035, respectively]. Schizophrenia was associated with higher mortality compared to BD or MDD. Cardiovascular diseases explained most of this excess mortality. Exploratory analyses suggested that psychotropic medications did not influence this excess mortality, except for antidepressants, which were associated with significantly reduced between-group difference in all-cause and cardiovascular mortality.

Lifetime exposure to unemployment and prior working conditions are associated with retiree's health: A retrospective study in a large population-based French cohort.

It is unclear whether unemployment exposure, as well as working conditions, can have sustained effects on the health of retirees who are no longer exposed. The aim of the present study is to investigate this issue in 29,281 French retirees from the CONSTANCES cohort in whom the prevalence of suboptimal self-rated health, disability for routine tasks, cardiovascular diseases and cancers is assessed according to lifetime exposure to unemployment and prior working conditions. The analyses are performed retrospectively using multivariable logistic regression models with adjustment for potential confounders such as sex, birth year, parental histories of cardiovascular disease and cancer, social position, retirement age and duration. High lifetime exposure to unemployment is associated with an increased prevalence of suboptimal self-rated health (adjusted odds ratio (95% CI), 1.39 (1.23-1.57)), disability for routine tasks (1.41 (1.26-1.57)) and several cardiovascular diseases including stroke (1.66 (1.19-2.31)), myocardial infarction (1.65 (1.18-2.31)) and peripheral arterial disease (2.38 (1.46-3.90)). Bad prior working conditions are associated with an increased prevalence of disability for routine tasks (1.17 (1.04-1.33)) and cancers (1.27 (1.04-1.54)), notably prostate cancer (1.60 (1.01-2.64)). These findings suggest that unemployment and working conditions have long-term health effects that may cumulate over lifetime, emphasizing that risk evaluation and preventive strategies in retirees, as in workers, should take into account the life-course of individuals in addition to traditional risk factors.

Antipsychotic use and 28-day mortality in patients hospitalized with COVID-19: A multicenter observational retrospective study.

Prior research has yielded conflicting results about the potential influence of antipsychotics in patients with COVID-19. In this multicenter retrospective study, we examined the association of antipsychotic use at admission with 28-day all-cause mortality in a sample of 59,021 adult patients hospitalized with COVID-19 from January 2020 to November 2021. In a 1:1 ratio matched analytic sample (N=1,454) accounting for age, sex, hospital, hospitalization period, the Elixhauser Comorbidity Index, other psychotropic medications, medications prescribed according to compassionate use or as part of a clinical trial, current diagnoses of psychiatric disorders, and clinical and biological markers of COVID-19 severity, antipsychotic use was not associated with 28-day mortality [23.5% (N=727) versus 18.6% (N=727); OR=1.16; 95%CI=0.89-1.51; p=0.280]. This association remained non-significant in exploratory analyses across all classes of antipsychotics and individual molecules, except for typical antipsychotics and loxapine, which were significantly linked to increased 28-day mortality, associations likely due to residual indication bias. Contrariwise, antipsychotics prescribed at daily doses higher than 200 mg of chlorpromazine-equivalents might be associated with reduced 28-day mortality when compared to patients not taking antipsychotics in the matched analytic sample [10.4% (N=154) versus 18.6% (N=727); AOR=0.56; 95%CI=0.31-0.96; p=0.040]. These results suggest that antipsychotic use, when prescribed at usual doses, are not be associated with 28-day mortality in patients hospitalized with COVID-19.

Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study.

Prior evidence indicates the potential central role of the acid sphingomyelinase (ASM)/ceramide system in the infection of cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 31 August 2022. We examined the association between the ongoing use of medications functionally inhibiting acid sphingomyelinase (FIASMA), which reduces the infection of cells with SARS-CoV-2 in vitro, upon hospital admission with 28-day all-cause mortality in a 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other medications (N = 9714). The univariate Cox regression model of the matched analytic sample showed that FIASMA medication use at admission was associated with significantly lower risks of 28-day mortality (HR = 0.80; 95% CI = 0.72-0.88; p < 0.001). In this multicenter observational study, the use of FIASMA medications was significantly and substantially associated with reduced 28-day mortality among adult patients hospitalized with COVID-19. These findings support the continuation of these medications during the treatment of SARS-CoV-2 infections. Randomized clinical trials (RCTs) are needed to confirm these results, starting with the molecules with the greatest effect size in the study, e.g., fluoxetine, escitalopram, and amlodipine.

Comorbidity patterns and mortality among hospitalized patients with psychiatric disorders and COVID-19

Objectives: To examine the association between psychiatric and non-psychiatric comorbidity and 28-day mortality among patients with psychiatric disorders and COVID-19. Methods: Multicenter observational retrospective cohort study of adult patients with psychiatric disorders hospitalized with laboratory-confirmed COVID-19 at 36 Greater Paris university hospitals (January 2020-May 2021) (n=3,768). First, we searched for different subgroups of patients according to their psychiatric and non-psychiatric comorbidities through cluster analysis. Next, we compared 28-day all-cause mortality rates across the identified clusters, while taking into account sex, age, and the number of medical conditions. Results: We found five clusters of patients with distinct psychiatric and non-psychiatric comorbidity patterns. Twenty-eight-day mortality in the cluster of patients with mood disorders was significantly lower than in other clusters. There were no significant differences in mortality across other clusters. Conclusion: All psychiatric and non-psychiatric conditions may be associated with increased mortality in patients with psychiatric disorders and COVID-19. The lower risk of death among patients with mood disorders might be in line with the potential beneficial effect of certain antidepressants in COVID-19, but requires further research. These findings may help identify at-risk patients with psychiatric disorders who should benefit from vaccine booster prioritization and other prevention measures.

Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.

The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.

Distinct cardiovascular and cancer burdens associated with social position, work environment and unemployment: a cross-sectional and retrospective study in a large population-based French cohort.

OBJECTIVES: Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks. DESIGN: A cross-sectional and retrospective observational study. SETTING: A population-based French cohort (CONSTANCES). PARTICIPANTS: 130 197 adults enrolled between 2012 and 2021 without missing values. PRIMARY OUTCOME MEASURES: The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors. RESULTS: While social position, work environment and unemployment exposure are strongly inter-related with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p<0.04 to p<0.0001) but not of stroke. In contrast, a bad work environment is associated with an increased prevalence of stroke (OR=1.29, p<0.01) but not of angina pectoris, myocardial infarction and peripheral arterial disease. Low social position is associated with an increased prevalence of cervical and lung cancers (OR=1.73 and 1.95, p<0.002 and p<0.03) and a decreased prevalence of skin cancer (OR=0.70, p<0.0001) while a bad work environment is associated with an increased prevalence of breast, skin, prostate and colon cancers (OR=1.31 to 2.91, p<0.0002 to p<0.0001). Unemployment exposure is not associated with the prevalence of any type of cancers. CONCLUSIONS: Social position, work environment and unemployment are associated with distinct cardiovascular and cancerous diseases that could add up during lifetime, they should therefore be considered all together in any preventive strategy.

Comorbidity Patterns and Mortality Among Hospitalized Patients with Psychiatric Disorders and COVID-19.

OBJECTIVE: To examine the association between psychiatric and non-psychiatric comorbidity and 28-day mortality among patients with psychiatric disorders and COVID-19. METHODS: We performed a multicenter observational retrospective cohort study of adult patients with psychiatric disorders hospitalized with laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals (January 2020-May 2021) (N=3,768). First, we searched for different subgroups of patients according to their psychiatric and non-psychiatric comorbidities through cluster analysis. Next, we compared 28-day all-cause mortality rates across the identified clusters, while taking into account sex, age, and the number of medical conditions. RESULTS: We found 5 clusters of patients with distinct psychiatric and non-psychiatric comorbidity patterns. Twenty-eight-day mortality in the cluster of patients with mood disorders was significantly lower than in other clusters. There were no significant differences in mortality across other clusters. CONCLUSIONS: All psychiatric and non-psychiatric conditions may be associated with increased mortality in patients with psychiatric disorders and COVID-19. The lower risk of death among patients with mood disorders might be in line with the potential beneficial effect of certain antidepressants in COVID-19, but requires further research. These findings help identify at-risk patients with psychiatric disorders who should benefit from vaccine booster prioritization and other prevention measures.

Impact of lithium on mortality among older adults with major psychiatric disorders: A 5-year prospective multicenter study.

OBJECTIVE: Prior studies report conflicting results about the association between lithium use and all-cause mortality. In addition, data are scarce on this association among older adults with psychiatric disorders. In this report, we sought to examine the associations of lithium use with all-cause mortality and specific causes of death (i.e., due to cardiovascular disorder, non-cardiovascular disease, accident, or suicide) among older adults with psychiatric disorders during a 5-year follow-up period. METHODS: In this observational epidemiological study, we used data from 561 patients belonging to a Cohort of individuals with Schizophrenia or Affective disorders aged 55-years or more (CSA). Patients taking lithium at baseline were first compared to patients not taking lithium, and then to patients taking (i) antiepileptics and (ii) atypical antipsychotics in sensitivity analyses. Analyses were adjusted for socio-demographic (e.g., age, gender), clinical characteristics (e.g., psychiatric diagnosis, cognitive functioning), and other psychotropic medications (e.g. benzodiazepines). RESULTS: There was no significant association between lithium use and all-cause mortality [AOR=1.12; 95%CI=0.45-2.79; p=0.810] or disease-related mortality [AOR=1.37; 95%CI=0.51-3.65; p=0.530]. None of the 44 patients taking lithium died from suicide, whereas 4.0% (N=16) of patients not receiving lithium did. CONCLUSION: These findings suggest that lithium may not be associated with all-cause or disease-related mortality and might be associated with reduced risk of suicide in this population. They argue against the underuse of lithium as compared with antiepileptics and atypical antipsychotics among older adults with mood disorders.

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study.

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19-0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53-5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54-1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

Risk of Death in Individuals Hospitalized for COVID-19 With and Without Psychiatric Disorders: An Observational Multicenter Study in France.

Background: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19 or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders has yet to be evaluated. Methods: We performed an observational, multicenter, retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. Results: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up period of 14.6 days (SD = 17.9), 326 of 857 (38.0%) patients with a diagnosis of psychiatric disorder died compared with 1276 of 14,311 (8.9%) patients without such a diagnosis (odds ratio 6.27, 95% CI 5.40-7.28, p < .01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (adjusted odds ratio 3.27, 95% CI 2.78-3.85, p < .01). However, additional adjustments for obesity and number of medical conditions resulted in a nonsignificant association (adjusted odds ratio 1.02, 95% CI 0.84-1.23, p = .86). Exploratory analyses after the same adjustments suggested that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. Conclusions: These findings suggest that the increased risk of COVID-19-related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population and not by the underlying psychiatric disease.

Psychiatric symptoms and mortality in older adults with major psychiatric disorders: results from a multicenter study.

Prior research suggests that certain psychiatric symptoms could be associated with increased risk of death. However, it remains unclear whether this association could rely on all or specific symptoms. In this report, we used data from a multicenter 5-year prospective study (N = 641) of older adults with an ICD-10 diagnosis of schizophrenia, bipolar disorder or major depressive disorder, recruited from French community psychiatric departments. We used a latent variable approach to disentangle the effects shared by all psychiatric symptoms (i.e., general psychopathology factor) and those specific to individual psychiatric symptoms, while adjusting for sociodemographic and clinical factors. Psychiatric symptoms were assessed face-to-face by psychiatrists trained to semi-structured interviews using the Brief Psychiatric Rating Scale (BPRS). Among older adults with major psychiatric disorders, we found that all psychiatric symptoms were associated with increased mortality, and that their effect on the 5-year mortality were exerted mostly through a general psychopathology dimension (ß = 0.13, SE = 0.05, p < 0.05). No BPRS item or lower order factor had a significant effect on mortality beyond and above the effect of the general psychopathology factor. Greater number of medical conditions, older age, male sex, and being hospitalized or institutionalized at baseline were significantly associated with this risk beyond the effect of the general psychopathology factor. Since psychiatric symptoms may affect mortality mainly through a general psychopathology dimension, biological and psychological mechanisms underlying this dimension should be considered as promising targets for interventions to decrease excess mortality of older individuals with psychiatric disorders.

Sleep Complaints Among Adults With Major Depressive Episode Are Associated With Increased Risk of Incident Psychiatric Disorders: Results From a Population-Based 3-Year Prospective Study.

Objective: Sleep alterations have been suggested as a cause and consequence of psychiatric disorders. In this context, we evaluated the incidence of psychiatric disorders following sleep complaints in adults with major depressive episode (MDE).Methods: In a large, nationally representative 3-year prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2), we used structural equation modeling to examine shared and specific effects of trouble falling asleep, early morning awakening, and hypersomnia on incidence of common comorbid DSM-IV disorders among patients with MDE. The analyses adjusted for sociodemographic and clinical characteristics, including sedative or tranquilizer use.Results: Among participants with MDE at Wave 1, 3-year incidence rates were dysthymia = 2.9%, general anxiety disorder = 8.2%, panic disorder = 3.4%, social anxiety disorder = 4.0%, specific phobia = 3.0%, alcohol use disorder = 8.1%, nicotine dependence = 6.2%, cannabis use disorder = 2.7%, and other drug use disorder = 4.9%. Participants with 3-year incident psychiatric disorders commonly had trouble falling asleep (67.6% for cannabis use disorder to 76.4% for panic disorder), early morning awakening (43.3% for cannabis use disorder to 55.6% for dysthymia), and hypersomnia (51.3% for nicotine use disorder to 72.1% for social anxiety disorder). The effects of the incident general psychopathology factor, representing mechanisms related to incidence of all psychiatric disorders, were exerted almost exclusively through a factor representing shared effect across all sleep complaints. Sleep complaints were associated with increased risk of incident psychiatric disorders, independent of sociodemographic and clinical characteristics.Conclusions: These findings suggest that sleep complaints should be clinically assessed in all psychiatric disorders, as these prodromal symptoms might constitute transdiagnostic biomarkers and therapeutic targets for prevention.

Metabolic syndrome and risk of death in older adults with major psychiatric disorders: Results from a 5-year prospective multicenter study.

OBJECTIVES: No study has explored the association of individual components of metabolic syndrome with mortality in older patients with psychiatric disorders. In this report, we examined whether metabolic syndrome or any of its components predicted mortality in a cohort of older adults with psychiatric disorders. METHODS: We used data from a multicenter 5-year prospective cohort, including 634 in- and out-patients with schizophrenia, bipolar or major depressive disorder. Metabolic syndrome was assessed at baseline following NCEP-ATPIII criteria. Cause of death was categorized as cardiovascular disorder (CVD) mortality, non-CVD disease-related mortality (e.g., infections), suicide and accident. RESULTS: 122 participants (44.0%) were diagnosed with metabolic syndrome at baseline. In the full sample, there was no significant association between metabolic syndrome or any of its components with all-cause, CVD and non-CVD mortality. However, for the subpopulation of older adults with major depressive disorder, metabolic syndrome was significantly associated with increased all-cause and disease-related mortality after adjustment for age, sex and smoking status (p = 0.032 and p = 0.036, respectively). There was a significant interaction between metabolic syndrome and psychiatric diagnoses indicating that in participants with major depressive disorder, metabolic syndrome had a significantly greater effect on all-cause mortality (p = 0.025) and on disease-related mortality (p = 0.008) than in participants with either bipolar disorder or schizophrenia. CONCLUSIONS: Our findings do not support an association between metabolic syndrome and increased mortality in older patients with major psychiatric disorders. Several explanations are discussed, including a survival bias, a lack of sensitivity of the used cut-offs and a ceiling effect of metabolic syndrome on mortality in this very high-risk population. The latter hypothesis could also explain the significant association between metabolic syndrome and mortality in the depressive subgroup, where a ceiling effect is yet to be reached, given the less marked premature mortality in depressive patients compared to those with bipolar disorder or schizophrenia.

Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease.

This cohort study examines the prevalence of contraindications to nirmatrelvir-ritonavir in patients hospitalized with COVID-19.

Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model.

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.

Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19.

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP−HP (Assistance Publique−Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35−0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41−0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.

A Comprehensive Model of Predictors of Recurrence or Persistence in Individuals With Panic Disorder: Results From a National 3-Year Prospective Study.

Objective: Multiple factors may influence the risk of recurrence or persistence of panic disorder, suggesting the need to combine them into an integrative model to develop more effective prevention strategies. In this report, we sought to build a comprehensive model of the 3-year risk of recurrence or persistence in individuals with panic disorder using a longitudinal, nationally representative study, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 1, 2001-2002; Wave 2, 2004-2005).Methods: We used structural equation modeling to simultaneously examine the effects of 5 broad groups of clinical factors previously identified as potential predictors of recurrence or persistence in adults with a past-year DSM-IV diagnosis of panic disorder (n = 775): (1) severity of panic disorder, (2) severity of comorbidity, (3) family history of psychiatric disorders, (4) sociodemographic characteristics, and (5) treatment-seeking behavior.Results: The 3-year rates of persistence and recurrence were 13.0% and 27.6%, respectively. A general psychopathology factor, representing the shared effect of all comorbid psychiatric disorders, panic disorder liability, a lower physical health-related quality of life, a greater number of stressful life events, and the absence of treatment-seeking behavior at baseline, significantly and independently predicted recurrence or persistence of symptoms between the two waves (all P < .05).Conclusions: This integrative model could help clinicians to identify individuals at high risk of recurrence or persistence of panic disorder and provide content for future research.

Retirement age does not modify the association of prior working conditions with self-rated health and mortality in retirees: results from a prospective study of retired French workers.

OBJECTIVE: It is unclear whether retirement age can modify the association of working conditions with health and mortality in retirees who are no longer exposed to these conditions. METHODS: The present study investigated this issue in a cohort of 13,378 French workers in whom self-rated health and mortality were measured over 15 years after statutory retirement. The analyses were also performed in homogenous clusters of workers differentiated on the basis of working conditions, social position, birth and retirement years. RESULTS: Bad working conditions before retirement, which were assessed using a global score combining 25 different occupational exposures, were associated with higher rates of suboptimum self-rated health and mortality in retirees after adjusting for retirement age, social position, demographics and health status before retirement. These rates were also substantially higher in the cluster of workers characterized by bad working conditions in comparison to other clusters. In contrast, retirement age was not associated with self-rated health or mortality after adjusting for working conditions, social position, demographics and health status before retirement. Likewise, no association of retirement age with self-rated health or mortality was found in any cluster of workers and no interactions were observed with any of these clusters. CONCLUSION: These results suggest that bad working conditions before retirement have long-term detrimental effects on health and mortality in retirees and that retirement age does not modulate these effects. Improving work environment rather than modifying retirement age should be prioritized to promote health and reduce mortality not only in workers but also in retirees.