The impact of the COVID-19 pandemic on the mental health of healthcare workers:study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study

BACKGROUND: Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia. METHODS: Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country’s income level. RESULTS: As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly. CONCLUSIONS: This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00127-021-02211-9

Major societal crises and suicide

Suicide is the leading cause of violent death and a major public health and clinical concern. Globally, suicide mortality has decreased over the last three decades, largely due to dramatic declines in pesticide poisonings in Asia. Recent suicide mortality trends, however, have been heterogeneous, and there have been increases in suicide in several countries and regions (e.g., the United States, Jamaica, Cameroon). Monitoring suicide rates is important for surveillance reasons as well as to generate causal hypotheses, two key components of suicide prevention efforts. Suicide increases following major societal crises, such as economic recessions, are often characterized by heterogeneity across population subgroups – with larger increases among vulnerable groups. Examining subgroups, even if evidence of an increase in suicide overall is absent, can guide identification of at-risk groups and development and implementation of targeted prevention strategies. In Spain, a country with one of the lowest suicide rates across Europe, there has been scientific debate regarding whether suicide increased following the 2008 economic recession. Most recent research suggests that suicide remained largely unchanged, but data are scarce on vulnerable groups among whom the downstream economic effects of the recession might have been more intense than in the general population. Following the initial COVID-19 pandemic outbreak, there was generalized concern that suicide rates would go up due to increases in bereavement and loss of loved ones, fear of contagion and death, increases in prevalence of mental health conditions, and negative economic effects of the pandemic and contagion control measures. Initial examinations of suicide trends, however, indicated that suicide mortality either remained unchanged or decreased in most locations across the globe during the initial months following the pandemic onset. Subsequent evidence of delayed increases in suicide in specific places (e.g., Japan), however, pointed out the importance of continued monitoring of suicide rates. In addition, there is increasing evidence that suicide rates during the COVID-19 era have changed heterogeneously across sociodemographic groups with higher vulnerability to specific pandemic-related stressors (e.g., higher suicide risk among minoritized people in the United States or women in Japan). There are no systematic reviews examining suicide during the COVID-19 era beyond the initial 6 months of the pandemic, and there has been no systematic assessment of the variation in suicide changes after the onset of the pandemic across place, over time, and across population subgroups. In Spain, there has also been substantial debate regarding the impact of the pandemic on suicide rates: two studies using a suboptimal methodological approach found somewhat contradictory results. No studies have examined suicide among population subgroups during the pandemic in Spain. The aim of this dissertation is to examine variations in suicide across population groups as defined by sociodemographic characteristics during major societal crises (i.e., the 2008 recession and the COVID-19 pandemic) in Spain, and variations across place, over time, and across sociodemographic groups globally. The first chapter uses two different approaches to age-period-cohort modelling to examine suicide between 2000 and 2019 in Spain, stratifying analyses by foreign-born status – the most salient marker of disadvantage in Spain, and further analyzing suicide among foreign-born individuals without Spanish citizenship – a proxy for lack of residency permit. I found that, while suicide following the recession remained stable among native-born men, it increased slightly among native-born women – largely due to cohort effects affecting middle-aged women, and markedly among foreign-born individuals – largely due to period effects. Suicide increased especially among foreign-born individuals without Spanish citizenship. Notably, access to specialized healthcare and welfare was interrupted for migrants without residency permit shortly following onset of the recession, in the context of austerity politics undertaken across Europe. These results highlight the moderating role of socioeconomic vulnerability on suicide risk during major economic crises. The second chapter is a systematic integrative review of the variation of population-based suicide estimates following the initial pandemic outbreak globally. In this review, I examine methodological features of all published studies examining suicide during the COVID-19 pandemic, highlighting the importance of addressing autocorrelation, non-stationarity, and seasonality in studies using an interrupted time-series analysis (ITSA) approach to test a causal question (i.e., to compare observed vs. expected or counterfactual suicide counts or rates). I also provide rationale to expect substantial heterogeneity in a so-called effect of the pandemic on suicide, given multiple versions of the exposure of interest that make it impossible to estimate a sole causal effect. I critically summarize the results overall with a focus on variation across place, over time, and across population subgroups. My findings indicate substantial geographical heterogeneity; a variable initial period of decreased suicide followed, in several locations, by delayed suicide increases – underscoring the importance of sustained monitoring of rates; and heterogeneity across population subgroups with larger suicide increases among groups at higher risk of suicide contagion and mortality (e.g., older adults, racially minoritized residents) and groups vulnerable to negative economic effects of the pandemic (e.g., groups overrepresented in hospitality and tourism jobs). The third chapter uses Seasonal Autoregressive Integrated Moving Average (SARIMA) prediction models, an approach to ITSA that can adequately deal with autoregression, non-stationarity, and seasonality, to predict monthly suicide counts between April and December 2020 in Spain had the pandemic not taken place. I do so overall and by sex- and age-group, and by foreign-born status in a set of sensitivity analyses, and I then compare observed vs. predicted suicides to determine if suicide increased. I find generalized higher-than-expected suicide rates during spring and summer of 2020, overall and across subgroups – especially among older males during the summer months. I discuss potential explanations and implications for decision-making of these findings considering the theoretical framework developed in chapters 1 and 2

Disengagement From Early Intervention Services for Psychosis: A Systematic Review

OBJECTIVE: Therapeutic benefits associated with early services for psychosis are influenced by the degree to which participants engage in treatment. The main objective of this review was to analyze rates of disengagement in early psychosis services and identify predictors of disengagement in these settings. METHODS: A systematic search for studies published in the 1966-2019 period was conducted in PubMed, Google Scholar, EBSCO, Ovid, and Embase. The Observational Cohort and Cross-Sectional Studies scale was used to assess the methodological quality of reports identified in this search. A revised version of the behavioral model of health service use was employed to evaluate and understand predictors of disengagement (categorized as predisposing, enabling, and need factors) identified in the studies with the highest quality. RESULTS: Twenty studies met the inclusion criteria. Disengagement rates (12% to 53%) and definitions of disengagement varied widely across these studies. Most did not find a compelling association between predisposing factors (e.g., age) and disengagement. Enabling factors, such as lack of family support and living alone, were consistently found to be related to increased disengagement across studies. Finally, need factors, such as lower medication adherence and higher drug misuse, were associated with higher risk for disengagement. CONCLUSIONS: Enabling and need factors seemed to be the most predictive of disengagement from early psychosis services. Substantial between-study variation in identified predictors of disengagement may be addressed by developing and applying a consensus definition of disengagement in future research

Predictors of Early Discharge From Early Intervention Services for Psychosis in New York State

OBJECTIVE: Although specialized early intervention services (EISs) for psychosis promote engagement in care, a substantial number of individuals who receive these services are discharged from care earlier than expected. The main goal of this study was to examine predictors of early discharge in a large sample of individuals enrolled in an EIS program in the United States. METHODS: This cohort study (N=1,349) used programmatic data from OnTrackNY, an EIS program that delivers evidence-based interventions to youths across New York State experiencing a first episode of nonaffective psychosis. The main outcome was “early discharge,” which was operationalized as discharge prior to completing 12 months of treatment. Cox proportional hazard regression models were used to assess the association between sociodemographic, clinical, and support system predictors and early discharge. RESULTS: The estimated probability of discharge before 1 year was 32%. Participants who at baseline had poor medication adherence, had no health insurance, were living alone or with nonparental family, or were using cannabis were at higher risk of leaving services within the first 12 months after enrollment. Individuals with higher social functioning were at lower risk of being discharged early from OnTrackNY, but those with higher occupational functioning were at a higher risk. CONCLUSIONS: Predictors of early discharge from EISs largely overlapped with previously identified predictors of poor prognosis in early psychosis. However, the association between early discharge and high occupational functioning indicates that trajectories leading up to discharge are heterogeneous

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used