Herpes zoster vaccination and new diagnoses of dementia: A quasi-randomized study in Australia.

Increasing evidence suggests that neurotropic herpesviruses could play a role in the development of dementia, possibly through a neuroinflammatory process. Herpes zoster (HZ) vaccination has been reported to lead to a reduced probability of being diagnosed with dementia in several correlational studies and in a prior analysis by our team in Wales. This present study constitutes the first investigation to use a quasi-randomized study design in an electronic health record dataset from a large and diverse nation (Australia) to aim to determine the effect of HZ vaccination on dementia. In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age through primary care providers. Thus, those whose 80th birthday was just a few days prior to November 1 2016 never became eligible, whereas those whose 80th birthday was just a few days later were eligible. The key advantage of our approach is that one would not expect that these population groups who differ in their age by only a minute degree would, on average, differ in any of their health characteristics and behaviors. We used detailed primary healthcare records with week-of-birth information from 65 general practices across Australia. We analyzed our data using a regression discontinuity approach. Our sample consisted of 101,219 patients. As expected, patients born just before versus shortly after the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination were well-balanced in their past preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 15.7 (95% CI: [12.2 - 19.3], p < 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the eligibility threshold. The eligibility rules of the HZ vaccination program, thus, created comparison groups just on either side of the date-of-birth eligibility threshold who were similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. Eligibility for HZ vaccination (i.e., being born shortly before versus shortly after November 2 1936) decreased the probability of receiving a new dementia diagnosis over 7.4 years by 2.0 percentage points (95% CI: [0.3 - 3.7], p = 0.021). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations), nor the probability of being diagnosed with other common chronic conditions than dementia. This study provides important evidence on the potential benefits of HZ vaccination for dementia because its quasi-randomized design allows for conclusions that are more likely to be causal than those of the existing associational evidence.

The prevalence of cardiovascular disease risk factors among adults living in extreme poverty.

Evidence on cardiovascular disease (CVD) risk factor prevalence among adults living below the World Bank's international line for extreme poverty (those with income <$1.90 per day) globally is sparse. Here we pooled individual-level data from 105 nationally representative household surveys across 78 countries, representing 85% of people living in extreme poverty globally, and sorted individuals by country-specific measures of household income or wealth to identify those in extreme poverty. CVD risk factors (hypertension, diabetes, smoking, obesity and dyslipidaemia) were present among 17.5% (95% confidence interval (CI) 16.7-18.3%), 4.0% (95% CI 3.6-4.5%), 10.6% (95% CI 9.0-12.3%), 3.1% (95% CI 2.8-3.3%) and 1.4% (95% CI 0.9-1.9%) of adults in extreme poverty, respectively. Most were not treated for CVD-related conditions (for example, among those with hypertension earning <$1.90 per day, 15.2% (95% CI 13.3-17.1%) reported taking blood pressure-lowering medication). The main limitation of the study is likely measurement error of poverty level and CVD risk factors that could have led to an overestimation of CVD risk factor prevalence among adults in extreme poverty. Nonetheless, our results could inform equity discussions for resource allocation and design of effective interventions.

Quasi-experimental evaluation of a nationwide diabetes prevention programme.

Diabetes is a leading cause of morbidity, mortality and cost of illness1,2. Health behaviours, particularly those related to nutrition and physical activity, play a key role in the development of type 2 diabetes mellitus3. Whereas behaviour change programmes (also known as lifestyle interventions or similar) have been found efficacious in controlled clinical trials4,5, there remains controversy about whether targeting health behaviours at the individual level is an effective preventive strategy for type 2 diabetes mellitus6 and doubt among clinicians that lifestyle advice and counselling provided in the routine health system can achieve improvements in health7-9. Here we show that being referred to the largest behaviour change programme for prediabetes globally (the English Diabetes Prevention Programme) is effective in improving key cardiovascular risk factors, including glycated haemoglobin (HbA1c), excess body weight and serum lipid levels. We do so by using a regression discontinuity design10, which uses the eligibility threshold in HbA1c for referral to the behaviour change programme, in electronic health data from about one-fifth of all primary care practices in England. We confirm our main finding, the improvement of HbA1c, using two other quasi-experimental approaches: difference-in-differences analysis exploiting the phased roll-out of the programme and instrumental variable estimation exploiting regional variation in programme coverage. This analysis provides causal, rather than associational, evidence that lifestyle advice and counselling implemented at scale in a national health system can achieve important health improvements.

The effect of herpes zoster vaccination on the occurrence of deaths due to dementia in England and Wales.

Background: The United Kingdom (UK) has used date of birth-based eligibility rules for live-attenuated herpes zoster (HZ) vaccination that have led to large differences in HZ vaccination coverage between individuals who differed in their age by merely a few days. Using this unique natural randomization, we have recently provided evidence from Welsh electronic health record data that HZ vaccination caused a reduction in new dementia diagnoses over a seven-year period. Based on this, we hypothesized that HZ vaccination may have slowed the dementia disease process more generally and, thus, already reduced deaths with dementia as their underlying cause even though the UK's HZ vaccination program commenced as recently as September 2013. Using country-wide death certificate data for England and Wales, this study, therefore, aimed to determine whether eligibility for HZ vaccination caused a reduction in deaths due to dementia over a nine-year follow-up period. Methods: Adults who had their 80th birthday shortly before September 1 2013 were ineligible for HZ vaccination in the UK's National Health Service and remained ineligible for life, whereas those who had their 80th birthday shortly after September 1 2013 (i.e., born on or after September 2 1933) were eligible for one year. Akin to a randomized trial, this date-of-birth threshold generated birth cohorts who are likely exchangeable in observed and unobserved characteristics except for a small difference in age and a large difference in HZ vaccination uptake. We used country-wide data from death certificates in England and Wales on underlying causes of death from September 1 2004 to August 31 2022 by ICD-10 code and month of birth. Our analysis compared the percentage of the population with a death due to dementia among the month-of-birth cohorts around the September 2 1933 eligibility threshold using a regression discontinuity design. The primary analyses used the maximal available follow-up period of nine years. Results: The study population included 5,077,426 adults born between September 1 1925 and August 31 1941 who were alive at the start of the HZ vaccination program. The month-of-birth cohorts around the September 2 1933 eligibility cutoff were well balanced in their occurrence of all-cause and cause-specific deaths (including deaths due to dementia) prior to the start of the vaccination program. We estimated that over a nine-year follow-up period, eligibility for HZ vaccination reduced the percentage of the population with a death due to dementia by 0.38 (95% CI: 0.08 to 0.68, p=0.012) percentage points, corresponding to a relative reduction of 4.8%. As in our prior analysis, this effect was stronger among women (-0.62 [95% CI: -1.06 to -0.19] percentage points, p=0.004) than among men (-0.11 [95% CI: -0.51 to 0.28] percentage points, p=0.574). The reduction in deaths due to dementia likely resulted in an increase in remaining life expectancy because we found that HZ vaccination eligibility reduced all-cause mortality but had no effect on deaths not due to dementia. An effect on deaths due to dementia at the September 2 date-of-birth eligibility threshold existed only since the year in which the HZ vaccination program was implemented. Conclusions: Our findings indicate that HZ vaccination improved cognitive function at a fairly advanced stage of the dementia disease process because most individuals whose underlying cause of death was dementia during our nine-year follow-up period were likely already living with dementia at the start of the HZ vaccination program. By using a different population, type of data, and outcome than our prior study in Welsh electronic health record data, this analysis adds to the evidence base that HZ vaccination slows, or potentially even prevents, the natural history of dementia.

Risk of Worsening Heart Failure and All-Cause Mortality Following COVID-19 Vaccination in Patients With Heart Failure: A Nationwide Real-World Safety Study.

BACKGROUND: Patients with heart failure are vulnerable to the SARS-CoV-2 infection. However, limited evidence exists on the safety of the SARS-CoV-2 mRNA vaccines in this patient population. The objective of this study was to investigate the risk of all-cause mortality, worsening heart failure, venous thromboembolism, and myocarditis associated with the mRNA vaccines in patients with heart failure. METHODS: Using Danish nationwide registries, 2 cohorts were constructed: (1) all prevalent heart failure patients in 2019 aged 40 to 95 years and (2) all prevalent heart failure patients in 2021 aged 40 to 95 years, who were vaccinated with either of the 2 mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the 2 cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure. To estimate standardized absolute risks, outcome-specific Cox regression analyses were performed. RESULTS: The total study population comprised 101 786 patients. The median age of the study population was 74 years (interquartile range, 66-81). The standardized risk of all-cause mortality within 90 days was 2.23% (95% CI, 2.10%-2.36%) in the vaccinated cohort and 2.56% (95% CI, 2.43%-2.70%) in the unvaccinated cohort (90-day risk difference, -0.33% [95% CI, -0.52% to -0.15%]). The standardized risk of worsening heart failure within 90 days was 1.10% (95% CI, -1.01% to 1.19%) in the 2021 (vaccinated) cohort and 1.08% (95% CI, 0.99%-1.17%) in the 2019 (unvaccinated) cohort (risk difference, 0.02% [95% CI, -0.11% to 0.15%]). No significant differences were found regarding venous thromboembolism or myocarditis. CONCLUSIONS: Receiving an mRNA vaccine was not associated with an increased risk of worsening heart failure, myocarditis, venous thromboembolism, or all-cause mortality.

The impact of face-mask mandates on all-cause mortality in Switzerland: a quasi-experimental study.

BACKGROUND: Whereas there is strong evidence that wearing a face mask is effective in reducing the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evidence on the impact of mandating the wearing of face masks on deaths from coronavirus disease 2019 (COVID-19) and all-cause mortality is more sparse and likely to vary by context. Focusing on a quasi-experimental setting in Switzerland, we aimed to determine (i) the effect of face-mask mandates for indoor public spaces on all-cause mortality; and (ii) how the effect has varied over time, and by age and sex. METHODS: Our analysis exploited the fact that between July and October 2020, nine cantons in Switzerland extended a face-mask mandate at different time points from being restricted to public transportation only to applying to all public indoor places. We used both a Difference-in-Differences approach with fixed-effects for canton and week and an event-study approach. RESULTS: In our main Difference-in-Differences model, the face-mask mandate was associated with a 0.3% reduction in all-cause mortality [95% confidence interval (CI): -3.4% to 2.7%; P = 0.818]. This null effect was confirmed in the event-study approach and a variety of robustness checks. Combining the face-mask mandate with social distancing rules led to an estimated 5.1% (95% CI: -7.9% to -2.4%; P = 0.001) reduction in all-cause mortality. CONCLUSIONS: Mandating face-mask use in public indoor spaces in Switzerland in mid-to-late 2020 does not appear to have resulted in large reductions in all-cause mortality in the short term. There is some suggestion that combining face-mask mandates with social distancing rules reduced all-cause mortality.