Instrumental Variables in Influenza Vaccination Studies:Mission Impossible?!

AbstractObjectivesUnobserved confounding has been suggested to explain the effect of influenza vaccination on mortality reported in several observational studies. An instrumental variable (IV) is strongly related to the exposure under study, but not directly or indirectly (through other variables) with the outcome. Theoretically, analyses using IVs to control for both observed and unobserved confounding may provide unbiased estimates of influenza vaccine effects. We assessed the usefulness of IV analysis in influenza vaccination studies.MethodsInformation on patients aged 65 years and older from the computerized Utrecht General Practitioner (GP) research database over seven influenza epidemic periods was pooled to estimate the association between influenza vaccination and all-cause mortality among community-dwelling elderly. Potential IVs included in the analysis were a history of gout, a history of orthopaedic morbidity, a history of antacid medication use, and GP-specific vaccination rates.ResultsUsing linear regression analyses, all possible IVs were associated with vaccination status: risk difference (RD) 7.8% (95% confidence interval [CI] 3.6%; 12.0%), RD 2.8% (95% CI 1.7%; 3.9%), RD 8.1% (95% CI 6.1%; 10.1%), and RD 100.0% (95% CI 89.0%; 111.0%) for gout, orthopaedic morbidity, antacid medication use, and GP-specific vaccination rates, respectively. Each potential IV, however, also appeared to be related to mortality through other observed confounding variables (notably age, sex, and comorbidity).ConclusionsThe potential IVs studied did not meet the necessary criteria, because they were (indirectly) associated with the outcome. These variables may, therefore, not be suited to assess unconfounded influenza vaccine effects through IV analysis

Epidemiology of heart failure

The heart failure syndrome has first been described as an emerging epidemic about 25 years ago. Today, because of a growing and ageing population, the total number of heart failure patients still continues to rise. However, the case mix of heart failure seems to be evolving. Incidence has stabilized and may even be decreasing in some populations, but alarming opposite trends have been observed in the relatively young, possibly related to an increase in obesity. In addition, a clear transition towards heart failure with a preserved ejection fraction has occurred. Although this transition is partially artificial, due to improved recognition of heart failure as a disorder affecting the entire left ventricular ejection fraction spectrum, links can be made with the growing burden of obesity-related diseases and with the ageing of the population. Similarly, evidence suggests that the number of patients with heart failure may be on the rise in low-income countries struggling under the double burden of communicable diseases and conditions associated with a Western-type lifestyle. These findings, together with the observation that the mortality rate of heart failure is declining less rapidly than previously, indicate we have not reached the end of the epidemic yet. In this review, the evolving epidemiology of heart failure is put into perspective, to discern major trends and project future directions

Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination

Aims To assess the yield of screening for atrial fibrillation (AF) with a hand-held single-lead electrocardiogram (ECG) device during influenza vaccination in primary care in the Netherlands. Methods and results We used the MyDiagnostick to screen for AF in persons who participated in influenza vaccination sessions of ten Dutch primary care practices. In case of suspected AF detection by the stick, the recorded 1-min ECG registrations were analysed by a cardiologist. We scrutinized electronic medical files of the general practitioners to obtain information about the cases screened. Multivariable logistic regression analysis was performed to predict the relation between patient characteristics and a new screen-detected diagnosis of AF. In total, 3269 persons were screened for AF during the influenza vaccination sessions of 10 general practitioner practices. As a result, 37 (1.1%) new cases of AF were detected. Prior transient ischeamic attack or stroke (OR 6.05; 95%CI 1.93-19.0), and age (OR 1.09 per year; 95% CI 1.05-1.14) were independent predictors for such newly screen-detected AF. Of the 37 screen-detected AF cases, 2.7% had a CHA2DS2-VASc of 0, 18.9% a score of 1, and 78.4% a score of 2 or more. The majority needed oral anticoagulant therapy. Conclusions Screening seems feasible with an easy to use single-lead, hand-held ECG device with automatic AF detection during influenza vaccination in primary care and results in a '1-day' yield of 1.1% new cases of AF. Trial registration clinicaltrials.gov NCT02006524

Main messages for primary care from the 2016 European Guidelines on cardiovascular disease prevention in clinical practice

In 2016, a new version of the European Guidelines on Cardiovascular Prevention was released, representing a partnership between the European Association for Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology (ESC) and nine European societies, including Wonca-Europe. The ESC guidelines underscore the importance of a lifetime approach to cardiovascular (CV) risk since both CV risk and prevention are dynamic and continuous as patients' age and/or accumulate co-morbidities. Healthy people of all ages should be encouraged to adopt a healthy lifestyle, as well as improved lifestyle and reduced risk factor levels are paramount in patients at increased risk of developing cardiovascular disease (CVD) and in those with established CVD. Healthcare professionals, and especially general practitioners, play an important role in helping patients achieve this and should set a personal example of healthy lifestyle behaviour. The ESC guidelines are based on 'to do' and 'not to do' messages. Of note, what remains uncertain is stated at the end of each dedicated chapter, confirming that guidelines are not absolute rules, and should be interpreted in the light of the healthcare worker's knowledge and experience, patient preferences and the local social, cultural and economic situation

Эффективная система охлаждения квантоскопов

Разработана каскадная компрессорная система охлаждения, реализующая цикл Линде с многокомпонентными рабочими телами, ресурс работы которой составляет 30 тыс. часов

Drug Registries and Approval of Drugs:Promises, Placebo, or a Real Success?

Purpose: As part of the approval process, regulatory authorities often require postauthorization studies that involve patient registries; it is unknown, however, whether such registry studies are adequately completed. We investigated whether registry studies for new drugs were performed as agreed at time of approval. Methods: This study reviewed protocols and follow-up reports for 73 registry studies that were proposed for 43 drugs approved by the Committee for Medicinal Products for Human Use in Europe in the period 2007 to 2010. Results: The data lock point of January 1, 2016, was taken to allow a 5-year follow-up period for each drug after approval. At that time, 2 studies (3%) in registries had been finalized, 19 registries (26%) had not enrolled any patients, and 52 studies (71%) were ongoing. The median enrollment was 31% (interquartile range [IQR], 6–104) of the required number of patients for 41 registry studies that had a predefined sample size, 30% (IQR, 2–101) for nonimposed registries, and 61% (IQR, 18–144) for imposed registries. Implications: Enrollment of patients into postapproval registries is poor, although the results for imposed registries seem better. Currently, registries only have a limited impact on resolving gaps in the knowledge of a drug's benefits and risks at time of marketing authorization

Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes

BACKGROUND: Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. METHODS: A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners’ Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. RESULTS: Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06–1.30) for atrial fibrillation, 1.66 (1.55–1.83) for ischaemic heart disease, and 2.36 (2.10–2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. CONCLUSION: There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-021-01313-7

Recurrence up to 3.5 years after antibiotic treatment of acute otitis media in very young Dutch children: survey of trial participants

Objective To determine the long term effects of antibiotic treatment for acute otitis media in young children