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

Long-term prognostic importance of a single pulmonary wedge pressure measurement after myocardial infarction: A ten-year follow-up study

To assess the influence on short- and long-term survival of haemodynamic variables measured after acute myocardial infarction, a 10-year prospective follow-up study was undertaken. A total of 304 patients (259 males, 45 females) discharged from hospital after myocardial infarction and under 66 years of age were studied. Haemodynamic variables measured shortly after admittance included pulmonary wedge pressure, mixed venous oxygen saturation, blood pressure and heart rate. In the analysis, adjustments were made for differences in age, gender, clinical parameters and cardiovascular risk factors. Pulmonary wedge pressure was found to be a strong and independent predictor of both short-term and long-term survival. A gradual increase of the 10-year mortality risk with elevated wedge pressure could be demonstrated (relative risk, 1.09/mmHg; 95% confidence interval, 1.04–1.15). Relative risks of patients in the three highest categories of wedge pressure, 12–15 mmHg, 15–19 mmHg and 19 mmHg and higher, compared with patients in the lowest category, lower than 12 mmHg, were 2.25 (95% CI, 1.11–4.55), 2.43 (95% CI, 1.20–4.92) and 2.57 (95% CI, 1.04–6.37), respectively. The other measured haemodynamic variables were found to be associated with short-term mortality only. In conclusion, haemodynamic measurements after myocardial infarction are of prognostic importance after discharge. A single measurement of an elevated wedge pressure in particular unfavourably influenced both short-term and long-term survival

Maatschappelijk vertrouwen in de varkenshouderij: Deel 1: managementsamenvatting en conclusies

De aanleiding voor het project met de ‘officiële’ titel ‘Maatschappelijk vertrouwen in de veehouderij, in het bijzonder in de varkenshouderij’ is het topsectordocument Agro & Food: De Nederlandse groeidiamant (2011). Hierin wordt gesteld dat maatschappelijk draagvlak van wezenlijk belang is voor de Agro & Foodsector. Het idee is dat technische oplossingen, zoals nieuwe stalsystemen, kunnen bijdragen aan het creëren van een positief beeld van de sector, maar waarschijnlijk niet voldoende zijn voor het herstel van maatschappelijk vertrouwen in de Agro & Foodsector in het algemeen en de varkenshouderij in het bijzonder. Maatschappelijk ver- en wantrouwen in voedsel en voedselproductie is vandaag de dag onverminderd actueel. De paardenvleesaffaire en de doorgaande stroom van berichten in de media dat er met voedsel wordt gefraudeerd, illustreren dit. Dat de Onderzoekraad voor Veiligheid momenteel onderzoek doet naar voedselveiligheidrisico’s in de vleesverwerkende industrie is eveneens tekenend. Maar het vraagstuk van maatschappelijk vertrouwen is niet nieuw. Het is een issue dat al langere tijd speelt. Mede met het oog hierop is veel geïnvesteerd in betere stalsystemen en regelgeving en zijn er diverse commissies en dialogen geweest. Toch is en blijft maatschappelijk vertrouwen en draagvlak delicaat en gebrekkig. Dit wordt door de sector als problematisch ervaren. Aan Wageningen UR is gevraagd een onderzoek te doen naar het maatschappelijk vertrouwen van de veehouderij, met de toespitsing op de varkenshouderij. Het onderzoek is tweeledig van karakter. Enerzijds gaat het om diagnose die tot doel heeft meer te begrijpen van maatschappelijk vertrouwen en van de mechanismen die tot wantouwen of tot vertrouwen leiden. Op basis hiervan heeft dit onderzoek, anderzijds, tot doel voorstellen te doen over (het ontwikkelen van) interventies die bijdragen aan verbetering van maatschappelijk vertrouwen

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

BackgroundAtrial 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.AimTo investigate the yield of opportunistic screening for AF in usual primary care using a single-lead ECG device.Design and settingA clustered, randomised controlled trial among patients aged &gt;= 65 years with no recorded AF status in the Netherlands from October 2014 to March 2016.MethodFifteen 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.ResultsIn 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.ConclusionOpportunistic 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 &gt;= 65 years in the community than usual care. For higher participation rates in future studies, more rigorous screening methods are needed.</p

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

Оптимизация лапароскопической методики лечения тератомы яичника у женщин репродуктивного возраста

В эксперименте и клиническими исследованиями показано влияние лучевой аргоновой коагуляции, биполярной коагуляции и эндоскопического ушивания яичников кетгутом при лапароскопическом лечении дермоидных кист яичников у пациенток с бесплодием на дальнейшую их репродуктивную функцию и развитие спаечного процесса в послеоперационном периоде.The influence of argon coagulation, bipolar coagulation and endoscopic suture of ovaries with catgut at laparoscopic treatment for dermoid ovarian cysts in infertile patients on the further reproductive function and development of adhesions after the surgery were investigated experimentally and clinically