The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis

BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust

Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries

BackgroundThe COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that at its most extreme, this may manifest itself in increased suicide rates.MethodsWe sourced real-time suicide data from around the world via a systematic internet search and recourse to our networks and the published literature. We used interrupted time series analysis to model the trend in monthly suicides prior to COVID-19 in each country/area-within-country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic. Countries/areas-within countries contributed data from at least 1 January 2019 to 31 July 2020 and potentially from as far back as 1 January 2016 until as recently as 31 October 2020. We conducted a primary analysis in which we treated 1 April to 31 July 2020 as the COVID-19 period, and two sensitivity analyses in which we varied its start and end dates (for those countries/areas-within-countries with data beyond July 2020).OutcomesWe sourced data from 21 countries (high income [n=16], upper-middle income [n=5]; whole country [n=10], area(s)-within-the-country [n=11]). In general, there does not appear to have been a significant increase in suicides since the pandemic began in the countries for which we had data. In fact, in a number of countries/areas-within-countries there appears to have been a decrease.InterpretationThis is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. It offers a consistent picture, albeit from high- and upper-middle income countries, of suicide numbers largely remaining unchanged or declining in the early months of the pandemic. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic impacts of the pandemic unfold

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Bile cast nephropathy causing acute kidney injury in a patient with nonfulminant acute hepatitis A

Hepatitis A is usually a benign self-limiting disease with few or no extrahepatic manifestations. Acute hepatitis A causing severe renal dysfunction is not very common, although described. Patients developing renal dysfunction post hepatitis A infection usually have prerenal acute kidney injury (AKI) or acute tubular necrosis due to vomiting, diarrhea, and poor fluid replacement. However, if renal dysfunction persists, other causes need to be evaluated. The term cholemic nephrosis or more specifically bile cast nephropathy has been described in the setting of cholestatic jaundice and decompensated liver failure where bilirubin levels reach above 20 mg/dL. Herein, we describe the clinical course of a patient who developed acute hepatitis A with severe liver dysfunction and subsequently AKI which persisted for six weeks. Renal biopsy showed the evidence of bile cast nephropathy. After six weeks of hemodialysis, urine output improved. He slowly recovered both hepatic and renal functions

SCOPE: Surveillance of COVID-19 in pregnancy- results of a multicentric ambispective case-control study on clinical presentation and maternal outcomes in India between April to November 2020.

ObjectiveTo determine the clinical manifestations, risk factors, treatment modalities and maternal outcomes in pregnant women with lab-confirmed COVID-19 and compare it with COVID-19 negative pregnant women in same age group.DesignMulticentric case-control study.Data sourcesAmbispective primary data collection through paper-based forms from 20 tertiary care centres across India between April and November 2020.Study populationAll pregnant women reporting to the centres with a lab-confirmed COVID-19 positive result matched with controls.Data qualityDedicated research officers extracted hospital records, using modified WHO Case Record Forms (CRF) and verified for completeness and accuracy.Statistical analysisData converted to excel files and statistical analyses done using STATA 16 (StataCorp, TX, USA). Odds ratios (ORs) with 95% confidence intervals (CI) estimated using unconditional logistic regression.ResultsA total of 76,264 women delivered across 20 centres during the study period. Data of 3723 COVID positive pregnant women and 3744 age-matched controls was analyzed. Of the positive cases 56·9% were asymptomatic. Antenatal complications like preeclampsia and abruptio placentae were seen more among the cases. Induction and caesarean delivery rates were also higher among Covid positive women. Pre-existing maternal co-morbidities increased need for supportive care. There were 34 maternal deaths out of the 3723(0.9%) positive mothers, while covid negative deaths reported from all the centres were 449 of 72,541 (0·6%).ConclusionCovid-19 infection predisposed to adverse maternal outcomes in a large cohort of Covid positive pregnant women as compared to the negative controls

Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries

69Background: The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world. Methods: We sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries’ ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms “suicide” and “cause of death”, before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis). Findings: We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales, Australia (RR 0·81 [95% CI 0·72–0·91]); Alberta, Canada (0·80 [0·68–0·93]); British Columbia, Canada (0·76 [0·66–0·87]); Chile (0·85 [0·78–0·94]); Leipzig, Germany (0·49 [0·32–0·74]); Japan (0·94 [0·91–0·96]); New Zealand (0·79 [0·68–0·91]); South Korea (0·94 [0·92–0·97]); California, USA (0·90 [0·85–0·95]); Illinois (Cook County), USA (0·79 [0·67–0·93]); Texas (four counties), USA (0·82 [0·68–0·98]); and Ecuador (0·74 [0·67–0·82]). Interpretation: This is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic effects of the pandemic unfold. Funding: None.reservedmixedPirkis J.; John A.; Shin S.; DelPozo-Banos M.; Arya V.; Analuisa-Aguilar P.; Appleby L.; Arensman E.; Bantjes J.; Baran A.; Bertolote J.M.; Borges G.; Brecic P.; Caine E.; Castelpietra G.; Chang S.-S.; Colchester D.; Crompton D.; Curkovic M.; Deisenhammer E.A.; Du C.; Dwyer J.; Erlangsen A.; Faust J.S.; Fortune S.; Garrett A.; George D.; Gerstner R.; Gilissen R.; Gould M.; Hawton K.; Kanter J.; Kapur N.; Khan M.; Kirtley O.J.; Knipe D.; Kolves K.; Leske S.; Marahatta K.; Mittendorfer-Rutz E.; Neznanov N.; Niederkrotenthaler T.; Nielsen E.; Nordentoft M.; Oberlerchner H.; O'Connor R.C.; Pearson M.; Phillips M.R.; Platt S.; Plener P.L.; Psota G.; Qin P.; Radeloff D.; Rados C.; Reif A.; Reif-Leonhard C.; Rozanov V.; Schlang C.; Schneider B.; Semenova N.; Sinyor M.; Townsend E.; Ueda M.; Vijayakumar L.; Webb R.T.; Weerasinghe M.; Zalsman G.; Gunnell D.; Spittal M.J.Pirkis, J.; John, A.; Shin, S.; DelPozo-Banos, M.; Arya, V.; Analuisa-Aguilar, P.; Appleby, L.; Arensman, E.; Bantjes, J.; Baran, A.; Bertolote, J. M.; Borges, G.; Brecic, P.; Caine, E.; Castelpietra, G.; Chang, S. -S.; Colchester, D.; Crompton, D.; Curkovic, M.; Deisenhammer, E. A.; Du, C.; Dwyer, J.; Erlangsen, A.; Faust, J. S.; Fortune, S.; Garrett, A.; George, D.; Gerstner, R.; Gilissen, R.; Gould, M.; Hawton, K.; Kanter, J.; Kapur, N.; Khan, M.; Kirtley, O. J.; Knipe, D.; Kolves, K.; Leske, S.; Marahatta, K.; Mittendorfer-Rutz, E.; Neznanov, N.; Niederkrotenthaler, T.; Nielsen, E.; Nordentoft, M.; Oberlerchner, H.; O'Connor, R. C.; Pearson, M.; Phillips, M. R.; Platt, S.; Plener, P. L.; Psota, G.; Qin, P.; Radeloff, D.; Rados, C.; Reif, A.; Reif-Leonhard, C.; Rozanov, V.; Schlang, C.; Schneider, B.; Semenova, N.; Sinyor, M.; Townsend, E.; Ueda, M.; Vijayakumar, L.; Webb, R. T.; Weerasinghe, M.; Zalsman, G.; Gunnell, D.; Spittal, M. J