Summary Background Although studies have provided estimates of premature deaths attributable to either heat or cold in selected countries, none has so far offered a systematic assessment across the ...whole temperature range in populations exposed to different climates. We aimed to quantify the total mortality burden attributable to non-optimum ambient temperature, and the relative contributions from heat and cold and from moderate and extreme temperatures. Methods We collected data for 384 locations in Australia, Brazil, Canada, China, Italy, Japan, South Korea, Spain, Sweden, Taiwan, Thailand, UK, and USA. We fitted a standard time-series Poisson model for each location, controlling for trends and day of the week. We estimated temperature–mortality associations with a distributed lag non-linear model with 21 days of lag, and then pooled them in a multivariate metaregression that included country indicators and temperature average and range. We calculated attributable deaths for heat and cold, defined as temperatures above and below the optimum temperature, which corresponded to the point of minimum mortality, and for moderate and extreme temperatures, defined using cutoffs at the 2·5th and 97·5th temperature percentiles. Findings We analysed 74 225 200 deaths in various periods between 1985 and 2012. In total, 7·71% (95% empirical CI 7·43–7·91) of mortality was attributable to non-optimum temperature in the selected countries within the study period, with substantial differences between countries, ranging from 3·37% (3·06 to 3·63) in Thailand to 11·00% (9·29 to 12·47) in China. The temperature percentile of minimum mortality varied from roughly the 60th percentile in tropical areas to about the 80–90th percentile in temperate regions. More temperature-attributable deaths were caused by cold (7·29%, 7·02–7·49) than by heat (0·42%, 0·39–0·44). Extreme cold and hot temperatures were responsible for 0·86% (0·84–0·87) of total mortality. Interpretation Most of the temperature-related mortality burden was attributable to the contribution of cold. The effect of days of extreme temperature was substantially less than that attributable to milder but non-optimum weather. This evidence has important implications for the planning of public-health interventions to minimise the health consequences of adverse temperatures, and for predictions of future effect in climate-change scenarios. Funding UK Medical Research Council.
From the end of February, the SARS-CoV-2 epidemic in Spain has been following the footsteps of that in Italy very closely. We have analyzed the trends of incident cases, deaths, and intensive care ...unit admissions (ICU) in both countries before and after their respective national lockdowns using an interrupted time-series design. Data was analyzed with quasi-Poisson regression using an interaction model to estimate the change in trends. After the first lockdown, incidence trends were considerably reduced in both countries. However, although the slopes have been flattened for all outcomes, the trends kept rising. During the second lockdown, implementing more restrictive measures for mobility, it has been a change in the trend slopes for both countries in daily incident cases and ICUs. This improvement indicates that the efforts overtaken are being successful in flattening the epidemic curve, and reinforcing the belief that we must hold on.
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The time stratified case cross-over approach is a popular alternative to conventional time series regression for analysing associations between time series of environmental exposures (air pollution, ...weather) and counts of health outcomes. These are almost always analyzed using conditional logistic regression on data expanded to case-control (case crossover) format, but this has some limitations. In particular adjusting for overdispersion and auto-correlation in the counts is not possible. It has been established that a Poisson model for counts with stratum indicators gives identical estimates to those from conditional logistic regression and does not have these limitations, but it is little used, probably because of the overheads in estimating many stratum parameters.
The conditional Poisson model avoids estimating stratum parameters by conditioning on the total event count in each stratum, thus simplifying the computing and increasing the number of strata for which fitting is feasible compared with the standard unconditional Poisson model. Unlike the conditional logistic model, the conditional Poisson model does not require expanding the data, and can adjust for overdispersion and auto-correlation. It is available in Stata, R, and other packages.
By applying to some real data and using simulations, we demonstrate that conditional Poisson models were simpler to code and shorter to run than are conditional logistic analyses and can be fitted to larger data sets than possible with standard Poisson models. Allowing for overdispersion or autocorrelation was possible with the conditional Poisson model but when not required this model gave identical estimates to those from conditional logistic regression.
Conditional Poisson regression models provide an alternative to case crossover analysis of stratified time series data with some advantages. The conditional Poisson model can also be used in other contexts in which primary control for confounding is by fine stratification.
Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, ...particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2.
In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts.
We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 106 copies per mL to 24% when the index case had a viral load of 1 × 1010 copies per mL or higher (adjusted odds ratio per log10 increase in viral load 1·3, 95% CI 1·1–1·5). Increased risk of transmission was also associated with household contact (3·0, 1·59–5·65) and age of the contact (per year: 1·02, 1·01–1·04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 107 copies per mL to greater than 66% for those with an initial viral load of 1 × 1010 copies per mL or higher (hazard ratio per log10 increase in viral load 1·12, 95% CI 1·05–1·20; p=0·0006). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5–10) for individuals with an initial viral load lower than 1 × 107 copies per mL to 6 days (4–8) for those with an initial viral load between 1 × 107 and 1 × 109 copies per mL, and 5 days (3–8) for those with an initial viral load higher than 1 × 109 copies per mL.
In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner.
YoMeCorono, Generalitat de Catalunya.
For the Catalan translation of the abstract see Supplementary Materials section.
Background: Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this ...context. Objective: We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application. Data sources and extraction: A search was made of the MEDLINE and EMBASE databases. Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. Data synthesis: The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design's application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level. Conclusions: The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use.
Recent investigations have reported a decline in the heat-related mortality risk during the last decades. However, these studies are frequently based on modeling approaches that do not fully ...characterize the complex temperature-mortality relationship, and are limited to single cities or countries.
We assessed the temporal variation in heat-mortality associations in a multi-country data set using flexible modelling techniques.
We collected data for 272 locations in Australia, Canada, Japan, South Korea, Spain, the United Kingdom, and the United States, with a total 20,203,690 deaths occurring in summer months between 1985 and 2012. The analysis was based on two-stage time-series models. The temporal variation in heat-mortality relationships was estimated in each location with time-varying distributed lag nonlinear models, expressed through an interaction between the transformed temperature variables and time. The estimates were pooled by country through multivariate meta-analysis.
Mortality risk due to heat appeared to decrease over time in several countries, with relative risks associated to high temperatures significantly lower in 2006 compared with 1993 in the United States, Japan, and Spain, and a nonsignificant decrease in Canada. Temporal changes are difficult to assess in Australia and South Korea due to low statistical power, and we found little evidence of variation in the United Kingdom. In the United States, the risk seems to be completely abated in 2006 for summer temperatures below their 99th percentile, but some significant excess persists for higher temperatures in all the countries.
We estimated a statistically significant decrease in the relative risk for heat-related mortality in 2006 compared with 1993 in the majority of countries included in the analysis.
Gasparrini A, Guo Y, Hashizume M, Kinney PL, Petkova EP, Lavigne E, Zanobetti A, Schwartz JD, Tobias A, Leone M, Tong S, Honda Y, Kim H, Armstrong BG. 2015. Temporal variation in heat-mortality associations: a multicountry study. Environ Health Perspect 123:1200-1207; http://dx.doi.org/10.1289/ehp.1409070.
There is strong evidence concerning the impact of heat stress on mortality, particularly from high temperatures. However, few studies to our knowledge emphasize the importance of hot nights, which ...may prevent necessary nocturnal rest.
In this study, we use hot-night duration and excess to predict daily cause-specific mortality in summer, using multiple cities across Southern Europe.
We fitted time series regression models to summer cause-specific mortality, including natural, respiratory, and cardiovascular causes, in 11 cities across four countries. We included a distributed lag nonlinear model with lags up to 7 days for hot night duration and excess adjusted by daily mean temperature. We summarized city-specific associations as overall-cumulative exposure-response curves at the country level using meta-analysis.
We found positive but generally nonlinear associations between relative risk (RR) of cause-specific mortality and duration and excess of hot nights. RR of duration associated with nonaccidental mortality in Portugal was 1.29 (95% confidence interval CI = 1.07, 1.54); other associations were imprecise, but we also found positive city-specific estimates for Rome and Madrid. Risk of hot-night excess ranged from 1.12 (95% CI = 1.05, 1.20) for France to 1.37 (95% CI = 1.26, 1.48) for Portugal. Risk estimates for excess were consistently higher than for duration.
This study provides new evidence that, over a wider range of locations, hot night indices are strongly associated with cause-specific deaths. Modeling the impact of thermal characteristics during summer nights on mortality could improve decisionmaking for preventive public health strategies.
To estimate the association between psychosocial risk factors in the workplace and musculoskeletal disorders (MSD) in nurses and aides.
Systematic review and meta-analysis.
An electronic search was ...performed using MEDLINE (Pubmed), Psychinfo, Web of Science, Tripdatabase, Cochrane Central Controlled Trials, NIOSHTIC and Joanna Briggs Institute of Systematic Reviews on Nursing and Midwifery, to identify observational studies assessing the role of psychosocial risk factors on MSD in hospital nurses and nursing aides.
Two reviewers independently assessed eligibility and extracted data. Quality assessment was conducted independently by two reviewers using an adapted version of the Standardized Quality Scale. Random-effects meta-analysis was performed by subsets based on specific anatomical site and the exposure to specific psychosocial risk factors. Heterogeneity for each subset of meta-analysis was assessed and meta-regressions were conducted to examine the source of heterogeneity among studies.
Twenty-four articles were included in the review, seventeen of which were selected for meta-analysis. An association was identified between high psychosocial demands–low job control with prevalent and incident low back pain (OR 1.56; 95% CI 1.22–1.99 and OR 1.52; 95% CI 1.14–2.01, respectively), prevalent shoulder pain (OR 1.89; 95% CI 1.53–2.34), prevalent knee pain (OR 2.21; 95% CI 1.07–4.54), and prevalent pain at any anatomical site (OR 1.38; 95% CI 1.09–1.75). Effort-reward imbalance was associated with prevalent MSD at any anatomical site (OR 6.13; 95% CI 5.32–7.07) and low social support with incident back pain (OR 1.82; 95% CI 1.43–2.32). Heterogeneity was generally low for most subsets of meta-analysis.
This meta-analysis suggests that psychosocial risk factors at the workplace are associated with MSD in hospital nurses and nursing aides. Although most preventive strategies at the workplace are focused on ergonomic risk factors, improving the psychosocial work environment might have an impact on reducing MSDs.
Few studies have examined variation in the associations between heat waves and mortality in an international context.
We aimed to systematically examine the impacts of heat waves on mortality with ...lag effects internationally.
We collected daily data of temperature and mortality from 400 communities in 18 countries/regions and defined 12 types of heat waves by combining community-specific daily mean temperature ≥90th, 92.5th, 95th, and 97.5th percentiles of temperature with duration ≥2, 3, and 4 d. We used time-series analyses to estimate the community-specific heat wave-mortality relation over lags of 0-10 d. Then, we applied meta-analysis to pool heat wave effects at the country level for cumulative and lag effects for each type of heat wave definition.
Heat waves of all definitions had significant cumulative associations with mortality in all countries, but varied by community. The higher the temperature threshold used to define heat waves, the higher heat wave associations on mortality. However, heat wave duration did not modify the impacts. The association between heat waves and mortality appeared acutely and lasted for 3 and 4 d. Heat waves had higher associations with mortality in moderate cold and moderate hot areas than cold and hot areas. There were no added effects of heat waves on mortality in all countries/regions, except for Brazil, Moldova, and Taiwan. Heat waves defined by daily mean and maximum temperatures produced similar heat wave-mortality associations, but not daily minimum temperature.
Results indicate that high temperatures create a substantial health burden, and effects of high temperatures over consecutive days are similar to what would be experienced if high temperature days occurred independently. People living in moderate cold and moderate hot areas are more sensitive to heat waves than those living in cold and hot areas. Daily mean and maximum temperatures had similar ability to define heat waves rather than minimum temperature. https://doi.org/10.1289/EHP1026.
Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a ...postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking.
We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days.
The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 95% confidence interval, 0.52 to 1.42). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported.
Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).
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