Impact of influenza vaccination on GP-diagnosed COVID-19 and all-cause mortality: a Dutch cohort study.

OBJECTIVES: As clinical presentation and complications of both viruses overlap, it was hypothesised that influenza vaccination was associated with lower general practitioner (GP)-diagnosed COVID-19 rates and lower all-cause mortality rates. STUDY DESIGN: From a primary care population-based cohort in the Netherlands, GP-diagnosed COVID-19 (between 10 March and 22 November 2020) and all-cause mortality events (between 30 December 2019 and 22 November 2020) were recorded. 223 580 persons were included, representing the influenza vaccination 2019 target group (all aged ≥60 years, and those <60 years with a medical indication). Proportional hazards regression analyses evaluated associations between influenza vaccination in 2019 and two outcomes: GP-diagnosed COVID-19 and all-cause mortality. Covariables were sex, age, comorbidities and number of acute respiratory infection primary care consultations in 2019. RESULTS: A slightly positive association (HR 1.15; 95% CI 1.08 to 1.22) was found between influenza vaccination in 2019 and GP-diagnosed COVID-19, after adjusting for covariables. A slightly protective effect for all-cause mortality rates (HR 0.90; 95% CI 0.83 to 0.97) was found for influenza vaccination, after adjusting for covariables. A subgroup analysis among GP-diagnosed COVID-19 cases showed no significant association between influenza vaccination in 2019 and all-cause mortality. CONCLUSIONS: Our hypothesis of a possibly negative association between influenza vaccination in 2019 and GP-diagnosed COVID-19 was not confirmed as we found a slightly positive association. A slightly protective effect on all-cause mortality was found after influenza vaccination, possibly by a wider, overall protective effect on health. Future research designs should include test-confirmed COVID-19 cases and controls, adjustments for behavioural, socioeconomic and ethnic factors and validated cause-specific mortality cases.

Influenza vaccination among Dutch general practitioners and their attitude toward influenza vaccination in the elderly.

Knowledge, attitudes and beliefs (KABs) toward influenza vaccination (IV) play a key role in HCWs' decisions to receive vaccination and can strongly influence patients' IV uptake. We examined the knowledge, attitudes and beliefs of GPs toward IV, exploring their opinion on IV in the elderly, mandatory HCW vaccination and the desirability of an IV trial in the elderly with hospitalization/mortality as effect measure. From November 2018 to March 2019, surveys were emailed to GPs and GP-practices (n = 1676) in three regions of the Netherlands. We assessed the self-reported IV in GPs, reasons for (not) advising IV to personnel, (not) supporting mandatory IV for personnel and (not) desiring a trial on IV in the elderly on hospitalization/mortality. Multivariable logistic regression models were used to determine predictors for GP IV. A total of 552 surveys were completed and 71.9% of the GPs reported receiving IV. Determinants for IV in GPs were male sex (aOR 1.62, 95%CI 1.06-2.49, p = .03) and age ≥60 y (aOR 5.25, 95%CI 1.51-18.32, p = .01). Seventy-nine percent of the GPs recommend IV for their practice personnel. Mandatory IV for personnel was supported by 41.2% of the GPs with GP self-reporting IV being the only determinant (aOR 10.03 (95%CI 5.69-17.70 p = .00)). An IV trial on hospitalization and/or mortality was desired by 60.5% of the GPs. We concluded that the majority of Dutch GPs receives IV and recommends IV to their personnel. These high rates along with the hesitancy of GPs toward mandatory HCW IV should be considered when policymakers decide on a mandate for IV in HCW in general.

[Influenza point-of-care test in the GP practice and Emergency Department; analytical accuracy and added value]. / Influenzasneltests voor de huisartsenpraktijk en SEH.

An influenza epidemic can greatly increase the workload in primary care and the emergency department (ED) and can even disrupt the healthcare system. It is difficult to diagnose influenza by history taking and physical examination. A fast diagnosis usinginfluenza point-of-care tests (POCTs) could reduce unnecessary antibiotic prescriptions, diagnostic tests, consultations and hospital admissions. Moreover, length of stay on EDs and length of admission could be shortened. The analytical accuracy of antigen detection tests for influenza is relatively low compared to the well performing RT-PCR assays (sensitivity and specificity approximately 95%). Only 1 randomized controlled trial has shown the effect of a (combined) RT-PCR assay for influenza detection on clinically relevant outcome measures. Observational research suggests that introduction of RT-PCR assays for influenza detection reduces length of stay on the ED and decreased time from sample reception to result. For practical reasons, we should embrace the introduction of RT-PCR assays for influenza detection on EDs. Before POCTs can be implemented in primary care (family medicine) the analytical accuracy and time to receive results should be improved and effects of its clinical impact should be proven.

Influenza vaccination in the elderly: 25 years follow-up of a randomized controlled trial. No impact on long-term mortality.

Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcome of influenza vaccination on mortality in the elderly by conducting a 25-year follow-up study of a RCT on the efficacy of influenza vaccination as baseline. The RCT had been conducted in the Netherlands 5 years before vaccination was recommended for those aged >65 and 17 years before recommending it for those aged >60. The RCT included 1838 community-dwelling elderly aged ≥ 60 that had received an intramuscular injection with the inactivated quadrivalent influenza vaccine (n = 927) or placebo (n = 911) during the 1991/1992 winter. In our follow-up study, outcomes included all-cause mortality, influenza-related mortality and seasonal mortality. Unadjusted and adjusted hazard ratios (HRs) were estimated by Cox regression and sub-hazard ratios (SHRs) by competing risk models. Secondary analyses included subgroup analyses by age and disease status. The vital status up to January 1, 2017 was provided in 1800/1838 (98%) of the cases. Single influenza vaccination did not reduce all-cause mortality when compared to placebo (adjusted HR 0.95, 95% CI 0.85-1.05). Also, no differences between vaccination and placebo group were shown for underlying causes of death or seasonal mortality. In those aged 60-64, median survival increased with 20.1 months (95% CI 2.4-37.9), although no effects on all-cause mortality (adjusted HR 0.86, 95% CI 0.72-1.03) could be demonstrated in survival analysis. In conclusion, this study did not demonstrate a statistically significant effect following single influenza vaccination on long-term mortality in community-dwelling elderly in general. We propose researchers designing future studies on influenza vaccination in the elderly to fit these studies for longer-term follow-up, and suggest age-group comparisons in observational research. Clinical trial registry number: NTR6179.

[Influenza vaccination in the elderly: is a trial on mortality ethically acceptable?] / Effect influenzavaccinatie op sterfte onder ouderen.

The effectiveness of influenza vaccination in the elderly has long been a topic of debate, fueled by the absence of direct evidence on its effect on mortality. It is argued that new placebo-controlled trials should be undertaken to resolve this uncertainty. However, such trials may be ethically questionable. We provide an overview of the ethical challenges of an influenza vaccine efficacy trial designed to evaluate mortality in the elderly. An important condition in the justification of a trial is the existence of genuine uncertainty regarding the answer to a research question. Therefore an extensive analysis of the existing levels of knowledge is needed to support the conclusion that an effect of vaccination on mortality is uncertain. Even if a so-called 'clinical equipoise' status applies, denying a control group vaccination would be problematic because vaccination is considered 'competent care' and withholding vaccination could substantially increase patients' risk for influenza and its complications. Given the high burden of disease and proven benefits of vaccination, the importance of a trial is unlikely to outweigh the risk patients are exposed to. While a placebo-controlled trial in vaccine refusers may be considered, such a trial is unlikely to meet methodological standards regarding trial size and generalizability. We conclude that a new trial is unlikely to provide a direct answer, let alone change current policy. At the same time, given the lack of consensus on this topic, we invite researchers considering vaccine efficacy trials on mortality to address the ethical challenges as discussed.

Influenza vaccination in the elderly: Is a trial on mortality ethically acceptable?

The effectiveness of influenza vaccination in the elderly has long been a topic of debate, fueled by the absence of direct evidence from randomized trials on its effect on mortality and the methodological limitations of observational studies pointing this direction. It is argued that new placebo-controlled trials should be undertaken to resolve this uncertainty. However, such trials may be ethically questionable. To bring this discussion forward, we provide a comprehensive overview of the ethical challenges of an influenza vaccine efficacy trial designed to evaluate mortality in the elderly. An important condition in the justification of a trial is the existence of genuine uncertainty in regard to the answer to a research question. Therefore an extensive analysis of the existing levels of knowledge is needed to support the conclusion that an effect of vaccination on mortality is uncertain. Even if a so called "clinical equipoise" status applies, denying a control group vaccination would be problematic because vaccination is considered "competent care" and withholding vaccination could substantially increase patients' risk for influenza and its complications. Given the high burden of disease and already proven benefits of vaccination, such a trial is unlikely to meet the Declaration of Helsinki stating that the importance of a trial must outweigh the risk patients are exposed to. While a placebo-controlled trial in vaccine refusers may be considered, such a trial is unlikely to meet substantial methodological barriers regarding trial size and generalizability. We conclude that a new trial is unlikely to provide for a direct answer, let alone change current policy. At the same time, given the lack of consensus on the ethical acceptability of a placebo-controlled trial on the effect of influenza vaccination on mortality in the elderly, we invite researchers considering such trials to address the ethical challenges discussed in this manuscript.

[A neonatal supracondylar humeral fracture resembling a plexus injury]. / Van plexuslaesie naar supracondylaire humerusfractuur: Een pasgeborene met bewegingsbeperking van de arm.

BACKGROUND: A supracondylar fracture of the distal humerus in the newborn is a rare injury that can occur during a traumatic partus. It can be difficult to make the correct diagnosis soon after birth. CASE DESCRIPTION: A neonate, born by a short fundal delivery in an otherwise minimally traumatic partus had reduced movement in the lower left arm on the first day of life. Physical examination and conventional radiography did not reveal any other abnormalities, suggesting a brachial plexus injury. As the arm movement did not improve, two weeks after birth radiographic investigations were repeated and a supracondylar humeral fracture was diagnosed. After a period of immobilisation without a plaster cast, the function of the elbow was completely restored in this otherwise healthy child. CONCLUSION: In neonates with a supracondylar humeral fracture clear clinical or radiological signs may be absent. According to the literature, ultrasonography is effective in revealing these fractures at an early stage. Generally, these fractures heal well without a plaster cast.