The perils of climate change: In utero exposure to temperature variability and birth outcomes in the Andean region

The discussion on the effects of climate change on human activity has primarily focused on how increasing temperature levels can impair human health. However, less attention has been paid to the effect of increased climate variability on health. We investigate how in utero exposure to temperature variability, measured as the fluctuations relative to the historical local temperature mean, affects birth outcomes in the Andean region. Our results suggest that exposure to a temperate one standard deviation relative to the municipality’s long-term temperature mean during pregnancy reduces birth weight by 20 g. and increases the probability a child is born with low birth weight by a 0.7 percentage point. We also explore potential channels driving our results and find some evidence that increased temperature variability can lead to a decrease in health care and increased food insecurity during pregnancy.     

Psychological and Social Work Factors as Predictors of Mental Distress and Positive Affect: A Prospective,Multilevel Study

Occupational health research has mainly addressed determinants of negative health effects, typically employing individual-level self-report data. The present study investigated individual- and department-level (means of each work unit) effects of psychological/social work factors on mental distress and positive affect. Employees were recruited from 63 Norwegian organizations, representing a wide variety of job types. A total of 4158 employees, in 918 departments, responded at baseline and at follow-up two years later. Multilevel linear regressions estimated individual- and department-level effects simultaneously, and accounted for clustering of data. Baseline exposures and average exposures over time ([T1+T2]/2) were tested. All work factors; decision control, role conflict, positive challenge, support from immediate superior, fair leadership, predictability during the next month, commitment to organization, rumors of change, human resource primacy, and social climate, were related to mental distress and positive affect at the individual and department level. However, analyses of baseline exposures adjusted for baseline outcome, demonstrated significant associations at the individual level only. Baseline “rumors of change” was related to mental distress only and baseline “predictability during the next month” was not a statistical significant predictor of either outcome when adjusted for outcome at baseline. Psychological and social work factors were generally related to mental distress and positive affect in a mirrored way. Impact of exposures seemed most pervasive at the individual level. However, department-level relations were also discovered. Supplementing individual-level measures with aggregated measures may increase understanding of working conditions influence on employees`health and well-being. Organizational improvements focusing on the work factors in the current study should be able to reduce distress and enhance positive affect. Furthermore, both targeting individual employees and redesigning working conditions at the work unit level seems important.     

A Systematic Review on Health Resilience to Economic Crises

Background

The health effects of recent economic crises differ markedly by population group. The objective of this systematic review is to examine evidence from longitudinal studies on factors influencing resilience for any health outcome or health behaviour among the general population living in countries exposed to financial crises.

Methods

We systematically reviewed studies from six electronic databases (EMBASE, Global Health, MEDLINE, PsycINFO, Scopus, Web of Science) which used quantitative longitudinal study designs and included: (i) exposure to an economic crisis; (ii) changes in health outcomes/behaviours over time; (iii) statistical tests of associations of health risk and/or protective factors with health outcomes/behaviours. The quality of the selected studies was appraised using the Quality Assessment Tool for Quantitative Studies. PRISMA reporting guidelines were followed.

Results

From 14,584 retrieved records, 22 studies met the eligibility criteria. These studies were conducted across 10 countries in Asia, Europe and North America over the past two decades. Ten socio-demographic factors that increased or protected against health risk were identified: gender, age, education, marital status, household size, employment/occupation, income/ financial constraints, personal beliefs, health status, area of residence, and social relations. These studies addressed physical health, mortality, suicide and suicide attempts, mental health, and health behaviours. Women’s mental health appeared more susceptible to crises than men’s. Lower income levels were associated with greater increases in cardiovascular disease, mortality and worse mental health. Employment status was associated with changes in mental health. Associations with age, marital status, and education were less consistent, although higher education was associated with healthier behaviours.

Conclusions

Despite widespread rhetoric about the importance of resilience, there was a dearth of studies which operationalised resilience factors. Future conceptual and empirical research is needed to develop the epidemiology of resilience.     

The effect of rosuvastatin in a murine model of influenza A infection

Rationale

HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza A infection in mice.

Methods

C57Bl/6 mice were treated daily with rosuvastatin (10 mg/kg/day) supplemented in chow (or control chow) beginning three days prior to infection with either A//Udorn/72 [H3N2] or A/WSN/33 [H1N1] influenza A virus (1×10⁵ pfu/mouse). Plaque assays were used to examine the effect of rosuvastatin on viral replication in vitro and in the lungs of infected mice. We measured cell count with differential, protein and cytokines in the bronchoalveolar lavage (BAL) fluid, histologic evidence of lung injury, and wet-to-dry ratio on Day 1, 2, 4, and 6. We also recorded daily weights and mortality.

Results

The administration of rosuvastatin had no effect on viral clearance of influenza A after infection. Weight loss, lung inflammation and lung injury severity were similar in the rosuvastatin and control treated mice. In the mice infected with influenza A (A/WSN/33), mortality was unaffected by treatment with rosuvastatin.

Conclusions

Statins did not alter the replication of influenza A in vitro or enhance its clearance from the lung in vivo. Statins neither attenuated the severity of influenza A-induced lung injury nor had an effect on influenza A-related mortality. Our data suggest that the association between HMG CoA reductase inhibitors and improved outcomes in patients with sepsis and pneumonia are not attributable to their effects on influenza A infection.     

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care,secondary care,and death registration data in the OpenSAFELY platform

BackgroundThere is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.Methods and findingsWith the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes.We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.ConclusionsIn this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Krishnan Bhaskaran and co-workers study health outcomes after admission with COVID-19 and subsequent discharge.     

Insights on the implications of COVID-19 mitigation measures for mental health

Given the unprecedented level and duration of mitigation policies during the 2020 COVID-19 pandemic, it is not surprising that the public and the media have raised important questions about the potential for negative mental health consequences of the measures. To answer them, natural variability in policy implementation across US states and over time was analyzed to determine if mitigation policies correlated with Google searches for terms associated with symptoms of depression and anxiety. Findings indicated that restaurant/bar limits and stay-at-home orders correlated with immediate increases in searches for isolation and worry but the effects tapered off two to four weeks after their respective peaks. Moreover, the policies correlated with a reduction in searches for antidepressants and suicide, thus revealing no evidence of increases in severe symptomatology. The policy implications of these findings are discussed.     

Improving the Rank Precision of Population Health Measures for Small Areas with Longitudinal and Joint Outcome Models

Objectives

The University of Wisconsin Population Health Institute has published the County Health Rankings since 2010. These rankings use population-based data to highlight health outcomes and the multiple determinants of these outcomes and to encourage in-depth health assessment for all United States counties. A significant methodological limitation, however, is the uncertainty of rank estimates, particularly for small counties. To address this challenge, we explore the use of longitudinal and pooled outcome data in hierarchical Bayesian models to generate county ranks with greater precision.

Methods

In our models we used pooled outcome data for three measure groups: (1) Poor physical and poor mental health days; (2) percent of births with low birth weight and fair or poor health prevalence; and (3) age-specific mortality rates for nine age groups. We used the fixed and random effects components of these models to generate posterior samples of rates for each measure. We also used time-series data in longitudinal random effects models for age-specific mortality. Based on the posterior samples from these models, we estimate ranks and rank quartiles for each measure, as well as the probability of a county ranking in its assigned quartile. Rank quartile probabilities for univariate, joint outcome, and/or longitudinal models were compared to assess improvements in rank precision.

Results

The joint outcome model for poor physical and poor mental health days resulted in improved rank precision, as did the longitudinal model for age-specific mortality rates. Rank precision for low birth weight births and fair/poor health prevalence based on the univariate and joint outcome models were equivalent.

Conclusion

Incorporating longitudinal or pooled outcome data may improve rank certainty, depending on characteristics of the measures selected. For measures with different determinants, joint modeling neither improved nor degraded rank precision. This approach suggests a simple way to use existing information to improve the precision of small-area measures of population health.     

Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

“The war is over – and I must go” Egon Schiele, 1890–1918.

     

Population Aging at Cross-Roads: Diverging Secular Trends in Average Cognitive Functioning and Physical Health in the Older Population of Germany

This paper uses individual-level data from the German Socio-Economic Panel to model trends in population health in terms of cognition, physical fitness, and mental health between 2006 and 2012. The focus is on the population aged 50–90. We use a repeated population-based cross-sectional design. As outcome measures, we use SF-12 measures of physical and mental health and the Symbol-Digit Test (SDT) that captures cognitive processing speed. In line with previous research we find a highly significant Flynn effect on cognition; i.e., SDT scores are higher among those who were tested more recently (at the same age). This result holds for men and women, all age groups, and across all levels of education. While we observe a secular improvement in terms of cognitive functioning, at the same time, average physical and mental health has declined. The decline in average physical health is shown to be stronger for men than for women and found to be strongest for low-educated, young-old men aged 50–64: the decline over the 6-year interval in average physical health is estimated to amount to about 0.37 SD, whereas average fluid cognition improved by about 0.29 SD. This pattern of results at the population-level (trends in average population health) stands in interesting contrast to the positive association of physical health and cognitive functioning at the individual-level. The findings underscore the multi-dimensionality of health and the aging process.     

Impact of air pollution and climate change on mental health outcomes: an umbrella review of global evidence

The impact of air pollution and climate change on mental health has recently raised strong concerns. However, a comprehensive overview analyzing the existing evidence while addressing relevant biases is lacking. This umbrella review systematically searched the PubMed/Medline, Scopus and PsycINFO databases (up to June 26, 2023) for any systematic review with meta-analysis investigating the association of air pollution or climate change with mental health outcomes. We used the R metaumbrella package to calculate and stratify the credibility of the evidence according to criteria (i.e., convincing, highly suggestive, suggestive, or weak) that address several biases, complemented by sensitivity analyses. We included 32 systematic reviews with meta-analysis that examined 284 individual studies and 237 associations of exposures to air pollution or climate change hazards and mental health outcomes. Most associations (n=195, 82.3%) involved air pollution, while the rest (n=42, 17.7%) regarded climate change hazards (mostly focusing on temperature: n=35, 14.8%). Mental health outcomes in most associations (n=185, 78.1%) involved mental disorders, followed by suicidal behavior (n=29, 12.4%), access to mental health care services (n=9, 3.7%), mental disorders-related symptomatology (n=8, 3.3%), and multiple categories together (n=6, 2.5%). Twelve associations (5.0%) achieved convincing (class I) or highly suggestive (class II) evidence. Regarding exposures to air pollution, there was convincing (class I) evidence for the association between long-term exposure to solvents and a higher incidence of dementia or cognitive impairment (odds ratio, OR=1.139), and highly suggestive (class II) evidence for the association between long-term exposure to some pollutants and higher risk for cognitive disorders (higher incidence of dementia with high vs. low levels of carbon monoxide, CO: OR=1.587; higher incidence of vascular dementia per 1 μg/m³ increase of nitrogen oxides, NO_x: hazard ratio, HR=1.004). There was also highly suggestive (class II) evidence for the association between exposure to airborne particulate matter with diameter ≤10 μm (PM₁₀) during the second trimester of pregnancy and the incidence of post-partum depression (OR=1.023 per 1 μg/m³ increase); and for the association between short-term exposure to sulfur dioxide (SO₂) and schizophrenia relapse (risk ratio, RR=1.005 and 1.004 per 1 μg/m³ increase, respectively 5 and 7 days after exposure). Regarding climate change hazards, there was highly suggestive (class II) evidence for the association between short-term exposure to increased temperature and suicide- or mental disorders-related mortality (RR=1.024), suicidal behavior (RR=1.012), and hospital access (i.e., hospitalization or emergency department visits) due to suicidal behavior or mental disorders (RR=1.011) or mental disorders only (RR=1.009) (RR values per 1°C increase). There was also highly suggestive (class II) evidence for the association between short-term exposure to increased apparent temperature (i.e., the temperature equivalent perceived by humans) and suicidal behavior (RR=1.01 per 1°C increase). Finally, there was highly suggestive (class II) evidence for the association between the temporal proximity of cyclone exposure and severity of symptoms of post-traumatic stress disorder (r=0.275). Although most of the above associations were small in magnitude, they extend to the entire world population, and are therefore likely to have a substantial impact. This umbrella review classifies and quantifies for the first time the global negative impacts that air pollution and climate change can exert on mental health, identifying evidence-based targets that can inform future research and population health actions.     

Menopausal hormone therapy and women’s health: An umbrella review

BackgroundThere remains uncertainty about the impact of menopausal hormone therapy (MHT) on women’s health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes.Methods and findingsWe searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412).ConclusionsMHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

In an umbrella review, Guo-Qiang Zhang and colleagues comprehensively summarize evidence on the benefits and harms of menopausal hormone therapy across diverse health outcomes.     

Estimating Mortality Derived from Indoor Exposure to Particles of Outdoor Origin

Following an extensive review of the literature, we further analyze the published data to examine the health effects of indoor exposure to particulate matter (PM) of outdoor origin. We obtained data on all-cause, cardiovascular, and respiratory mortality per 10 μg/m³ increase in outdoor PM₁₀ or PM_2.5; the infiltration factors for buildings; and estimated time spent outdoors by individuals in the United States, Europe, China, and globally. These data were combined log-linear exposure–response model to estimate the all-cause, cardiovascular, and respiratory mortality of exposure to indoor PM pollution of outdoor origin. Indoor PM pollution of outdoor origin is a cause of considerable mortality, accounting for 81% to 89% of the total increase in mortality associated with exposure to outdoor PM pollution for the studied regions. The findings suggest that enhancing the capacity of buildings to protect occupants against exposure to outdoor PM pollution has significant potential to improve public health outcomes.     

Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

Household environmental tobacco smoke and risks of asthma,wheeze and bronchitic symptoms among children in Taiwan

Background

Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS) exposure remains inconsistent.

Methods

We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children''s exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms.

Results

The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02), but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87).

Conclusion

We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.     

The effect of universal influenza immunization on mortality and health care use

Background

In 2000, Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free influenza vaccines for the entire population aged 6 mo or older. Influenza immunization increased more rapidly in younger age groups in Ontario compared to other Canadian provinces, which all maintained targeted immunization programs. We evaluated the effect of Ontario''s UIIP on influenza-associated mortality, hospitalizations, emergency department (ED) use, and visits to doctors'' offices.

Methods and Findings

Mortality and hospitalization data from 1997 to 2004 for all ten Canadian provinces were obtained from national datasets. Physician billing claims for visits to EDs and doctors'' offices were obtained from provincial administrative datasets for four provinces with comprehensive data. Since outcomes coded as influenza are known to underestimate the true burden of influenza, we studied more broadly defined conditions. Hospitalizations, ED use, doctors'' office visits for pneumonia and influenza, and all-cause mortality from 1997 to 2004 were modelled using Poisson regression, controlling for age, sex, province, influenza surveillance data, and temporal trends, and used to estimate the expected baseline outcome rates in the absence of influenza activity. The primary outcome was then defined as influenza-associated events, or the difference between the observed events and the expected baseline events. Changes in influenza-associated outcome rates before and after UIIP introduction in Ontario were compared to the corresponding changes in other provinces. After UIIP introduction, influenza-associated mortality decreased more in Ontario (relative rate [RR] = 0.26) than in other provinces (RR = 0.43) (ratio of RRs = 0.61, p = 0.002). Similar differences between Ontario and other provinces were observed for influenza-associated hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.69, ratio of RRs = 0.45, p < 0.001), and doctors'' office visits (RR = 0.21 versus 0.52, ratio of RRs = 0.41, p < 0.001). Sensitivity analyses were carried out to assess consistency, specificity, and the presence of a dose-response relationship. Limitations of this study include the ecological study design, the nonspecific outcomes, difficulty in modeling baseline events, data quality and availability, and the inability to control for potentially important confounders.

Conclusions

Compared to targeted programs in other provinces, introduction of universal vaccination in Ontario in 2000 was associated with relative reductions in influenza-associated mortality and health care use. The results of this large-scale natural experiment suggest that universal vaccination may be an effective public health measure for reducing the annual burden of influenza.     

Examining the health effects and bioactive components in Agaricus bisporus mushrooms: a scoping review

There is evidence from both in vitro and animal models that the consumption of edible mushrooms has beneficial effects on health. It is unclear whether similar effects exist in humans and which bioactive compounds are present. This review synthesises the evidence on the world's most commonly consumed mushroom, Agaricus bisporus to (i) examine its effect on human health outcomes; and (ii) determine the nutrient density of its bioactive compounds, which may explain their health effects. A systematic literature search was conducted on the consumption of A. bisporus, without date and study design limits. Bioactive compounds included ergosterol, ergothioneine, flavonoids, glucans and chitin. Two authors independently identified studies for inclusion and assessed methodological quality. Beneficial effects of A. bisporus on metabolic syndrome, immune function, gastrointestinal health and cancer, with the strongest evidence for the improvement in Vitamin D status in humans, were found. Ultraviolet B (UVB) exposed mushrooms may increase and maintain serum 25(OH)D levels to a similar degree as vitamin D supplements. A. bisporus contain beta-glucans, ergosterol, ergothioneine, vitamin D and an antioxidant compound usually reported as flavonoids; with varying concentrations depending on the type of mushroom, cooking method and duration, and UVB exposure. Further research is required to fully elucidate the bioactive compounds in mushrooms using vigorous analytical methods and expand the immunological markers being tested. To enable findings to be adopted into clinical practice and public health initiatives, replication of existing studies in different population groups is required to confirm the impact of A. bisporus on human health.     

The long-run heterogeneous effects of a cholera pandemic on stature: Evidence from industrializing Japan

The recent COVID-19 pandemic poses the general question on how infectious diseases can persistently affect human health. A growing body of literature has found a significant amount of evidence on the long-term adverse effects of infectious diseases, such as influenza, typhoid fever, and yellow fever. However, we must be careful about the fact that little is known about the long-term consequences of the acute diarrheal disease pandemic cholera – Vibrio cholerae bacillus – which still threatens the health of the population in many developing countries. To bridge this gap in the body of knowledge, we utilized unique census-based data on army height at age 20 in early 20th-century Japan, with a difference-in-differences estimation strategy using regional variation in the intensity of cholera pandemics. We found that early-life exposure to a cholera pandemic had heterogeneous stunting effects on the final height of men; the magnitude of the stunting effects increased as the intensity of exposure increased.     

Prenatal influenza vaccination and allergic and autoimmune diseases in childhood: A longitudinal,population-based linked cohort study

BackgroundFew studies have evaluated the effect of maternal influenza vaccination on the development of allergic and autoimmune diseases in children beyond 6 months of age. We aimed to investigate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and subsequent diagnosis of allergic and autoimmune diseases.Methods and findingsThis longitudinal, population-based linked cohort study included 124,760 singleton, live-born children from 106,206 mothers in Western Australia (WA) born between April 2012 and July 2016, with up to 5 years of follow-up from birth. In our study cohort, 64,169 (51.4%) were male, 6,566 (5.3%) were Aboriginal and/or Torres Strait Islander children, and the mean age at the end of follow-up was 3.0 (standard deviation, 1.3) years. The exposure was receipt of seasonal IIV during pregnancy. The outcomes were diagnosis of an allergic or autoimmune disease, including asthma and anaphylaxis, identified from hospital and/or emergency department (ED) records. Inverse probability of treatment weights (IPTWs) accounted for baseline probability of vaccination by maternal age, Aboriginal and/or Torres Strait Islander status, socioeconomic status, body mass index, parity, medical conditions, pregnancy complications, prenatal smoking, and prenatal care. The models additionally adjusted for the Aboriginal and/or Torres Strait Islander status of the child. There were 14,396 (11.5%) maternally vaccinated children; 913 (6.3%) maternally vaccinated and 7,655 (6.9%) maternally unvaccinated children had a diagnosis of allergic or autoimmune disease, respectively. Overall, maternal influenza vaccination was not associated with diagnosis of an allergic or autoimmune disease (adjusted hazard ratio [aHR], 1.02; 95% confidence interval [CI], 0.95 to 1.09). In trimester-specific analyses, we identified a negative association between third trimester influenza vaccination and the diagnosis of asthma (n = 40; aHR, 0.70; 95% CI, 0.50 to 0.97) and anaphylaxis (n = 36; aHR, 0.67; 95% CI, 0.47 to 0.95).We did not capture outcomes diagnosed in a primary care setting; therefore, our findings are only generalizable to more severe events requiring hospitalization or presentation to the ED. Due to small cell sizes (i.e., <5), estimates could not be determined for all outcomes after stratification.ConclusionsIn this study, we observed no association between in utero exposure to influenza vaccine and diagnosis of allergic or autoimmune diseases. Although we identified a negative association of asthma and anaphylaxis diagnosis when seasonal IIV was administered later in pregnancy, additional studies are needed to confirm this. Overall, our findings support the safety of seasonal inactivated influenza vaccine during pregnancy in relation to allergic and autoimmune diseases in early childhood and support the continuation of current global maternal vaccine programs and policies.

Damien Foo and colleagues evaluate the association between prenatal influenza vaccination and diagnosis of allergic and autoimmune diseases in childhood.     

STOPPIT Baby Follow-Up Study: The Effect of Prophylactic Progesterone in Twin Pregnancy on Childhood Outcome

Objectives

To determine the long-term effects of in utero progesterone exposure in twin children.

Methods

This study evaluated the health and developmental outcomes of all surviving children born to mothers who participated in a double-blind, placebo-controlled trial of progesterone given for the prevention of preterm birth in twin pregnancies (STOPPIT, ISRCTN35782581). Follow-up was performed via record linkage and two parent-completed validated questionnaires, the Child Development Inventory and the Health Utilities Index.

Results

Record linkage was successfully performed on at least one record in 759/781 (97%) children eligible for follow-up. There were no differences between progesterone-exposed and placebo-exposed twins with respect to incidence of death, congenital anomalies and hospitalisation, nor on routine national child health assessments. Questionnaire responses were received for 324/738 (44%) children. The mean age at questionnaire follow-up was 55.5 months. Delay in at least one developmental domain on the Child Development Inventory was observed in 107/324 (33%) children, with no evidence of difference between progesterone-exposed and placebo-exposed twins. There was no evidence of difference between the progesterone and placebo groups in global health status assessed using the Health Utilities Index: 89% of children were rated as having ‘excellent’ health and a further 8% as having ‘very good’ health.

Conclusions

In this cohort of twin children there was no evidence of a detrimental or beneficial impact on health and developmental outcomes at three to six years of age due to in utero exposure to progesterone.     

Increased Mortality Exposure within the Family Rather than Individual Mortality Experiences Triggers Faster Life-History Strategies in Historic Human Populations

Life History Theory predicts that extrinsic mortality risk is one of the most important factors shaping (human) life histories. Evidence from contemporary populations suggests that individuals confronted with high mortality environments show characteristic traits of fast life-history strategies: they marry and reproduce earlier, have shorter birth intervals and invest less in their offspring. However, little is known of the impact of mortality experiences on the speed of life histories in historical human populations with generally higher mortality risk, and on male life histories in particular. Furthermore, it remains unknown whether individual-level mortality experiences within the family have a greater effect on life-history decisions or family membership explains life-history variation.In a comparative approach using event history analyses, we study the impact of family versus individual-level effects of mortality exposure on two central life-history parameters, ages at first marriage and first birth, in three historical human populations (Germany, Finland, Canada). Mortality experience is measured as the confrontation with sibling deaths within the natal family up to an individual''s age of 15.Results show that the speed of life histories is not adjusted according to individual-level mortality experiences but is due to family-level effects. The general finding of lower ages at marriage/reproduction after exposure to higher mortality in the family holds for both females and males. This study provides evidence for the importance of the family environment for reproductive timing while individual-level mortality experiences seem to play only a minor role in reproductive life history decisions in humans.