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

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

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

Opportunistic screening versus usual care for diagnosing atrial fibrillation in general practice:a cluster randomised controlled trial

Background Atrial fibrillation [AF] increases the risk of stroke, heart failure, and all-cause mortality. AF may be asymptomatic and therefore remain undiagnosed. Devices such as single-lead electrocardiographs [ECGs] may help GPs to diagnose AF. Aim To investigate the yield of opportunistic screening for AF in usual primary care using a single-lead ECG device. Design and setting A clustered, randomised controlled trial among patients aged >= 65 years with no recorded AF status in the Netherlands from October 2014 to March 2016. Method Fifteen intervention general practices used a single-lead ECG device at their discretion and 16 control practices offered usual care. The follow-up period was 1 year, and the primary outcome was the proportion of newly diagnosed cases of AF. Results In total. 17 107 older people with no recorded AF status were eligible to participate in the study. In the intervention arm. 10.7% of eligible patients [n = 919] were screened over the duration of the study year. The rate of newly diagnosed AF was similar in the intervention and control practices [1.43% versus 1.37%, P= 0.73]. Screened patients were more likely to have comorbidities, such as hypertension [60.0% versus 48.7%], type 2 diabetes [24.3% versus 18.6%], and chronic obstructive pulmonary disease [11.3% versus 7.4%], than eligible patients not screened in the intervention arm. Among patients with newly diagnosed AF in intervention practices. 27% were detected by screening, 23% by usual primary care. and 50% by a medical specialist or after stroke/transient ischaemic attack. Conclusion Opportunistic screening with a single-lead ECG at the discretion of the GP did not result in a higher yield of newly detected cases of AF in patients aged >= 65 years in the community than usual care. For higher participation rates in future studies, more rigorous screening methods are needed

The importance of cardiovascular disease for mortality in patients with COPD: a prognostic cohort study

Background. Cardiovascular diseases are the major cause of mortality in patients with chronic obstructive pulmonary disease (COPD), however, are rarely considered in prediction models in patients with COPD. Objective. To quantify the effect of cardiovascular determinants on mortality in patients with a GP's diagnosis of COPD. Methods. Four hundred and five patients aged >65 years with a diagnosis of COPD (244 with COPD by spirometry) were followed up for an average period of 4.2 (SD 1.4) years. Cox proportional hazard regression analyses with bootstrapping techniques were performed to identify independent predictors of all-cause mortality. Results. In multivariable analysis, all-cause mortality was best predicted by age [hazard ratio Conclusions. Physicians should consider ischaemic heart disease in the clinical evaluation of any patient with a GP's diagnosis of COPD. Angina pectoris on history taking is a strong predictor of all-cause mortality in these patients and should be treated adequately to improve prognosis