Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis

BACKGROUND: Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and CINAHL Complete databases for articles published from Jan 1, 2016, to June 13, 2022, and Web of Science for studies published from database inception to June 13, 2022. For studies published before Jan 1, 2016, we consulted published systematic reviews. Two reviewers (EJ-G and EJR) independently screened, extracted data using a data collection form, assessed studies' risk of bias using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) and evaluated the weight of evidence by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included observational studies and randomised controlled trials that reported vaccine effectiveness against influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B using four vaccination groups: current season; previous season; current and previous seasons; and neither season (reference). For each study, we calculated the absolute difference in vaccine effectiveness (ΔVE) for current season only and previous season only versus current and previous season vaccination to estimate attenuation associated with repeated vaccination. Pooled vaccine effectiveness and ∆VE were calculated by season, age group, and overall. This study is registered with PROSPERO, CRD42021260242. FINDINGS: We identified 4979 publications, selected 681 for full review, and included 83 in the systematic review and 41 in meta-analyses. ΔVE for vaccination in both seasons compared with the current season was -9% (95% CI -16 to -1, I2=0%; low certainty) for influenza A(H1N1)pdm09, -18% (-26 to -11, I2=7%; low certainty) for influenza A(H3N2), and -7% (-14 to 0, I2=0%; low certainty) for influenza B, indicating lower protection with consecutive vaccination. However, for all types, A subtypes and B lineages, vaccination in both seasons afforded better protection than not being vaccinated. INTERPRETATION: Our estimates suggest that, although vaccination in the previous year attenuates vaccine effectiveness, vaccination in two consecutive years provides better protection than does no vaccination. The estimated effects of vaccination in the previous year are concerning and warrant additional investigation, but are not consistent or severe enough to support an alternative vaccination regimen at this time. FUNDING: WHO and the US National Institutes of Health

Key challenges for the surveillance of respiratory viruses: transitioning out of the acute phase of the SARS-CoV-2 pandemic

To support the ongoing management of viral respiratory diseases, many countries are moving towards an integrated model of surveillance for SARS-CoV-2, influenza, and other respiratory pathogens. While many surveillance approaches catalysed by the COVID-19 pandemic provide novel epidemiological insight, continuing them as implemented during the pandemic is unlikely to be feasible for non-emergency surveillance, and many have already been scaled back. Furthermore, given anticipated co-circulation of SARS-CoV-2 and influenza, surveillance activities in place prior to the pandemic require review and adjustment to ensure their ongoing value for public health. In this perspective, we highlight key challenges for the development of integrated models of surveillance. We discuss the relative strengths and limitations of different surveillance practices and studies, their contribution to epidemiological assessment, forecasting, and public health decision making

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute.Fil: Mukkada, Sheena. St Jude Children's Research Hospital; Estados UnidosFil: Bhakta, Nickhill. St Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Hospital Sant Joan de Déu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chen, Yichen. St Jude Children's Research Hospital; Estados UnidosFil: Vedaraju, Yuvanesh. St Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R. St Jude Children's Research Hospital; Estados UnidosFil: Muniz Talavera, Hilmarie. St Jude Children's Research Hospital; Estados UnidosFil: Ranadive, Radhikesh. St Jude Children's Research Hospital; Estados UnidosFil: Metzger, Monika. St Jude Children's Research Hospital; Estados UnidosFil: Friedrich, Paola. St Jude Children's Research Hospital; Estados UnidosFil: Agulnik, Asya. St Jude Children's Research Hospital; Estados UnidosFil: Jeha, Sima. St Jude Children's Research Hospital; Estados UnidosFil: Lam, Catherine G.. St Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Moreira, Daniela. St Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor M. St Jude Children's Research Hospital; Estados UnidosFil: Sullivan, Michael. University of Melbourne; AustraliaFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; CanadáFil: Caniza, Miguela A.. St Jude Children's Research Hospital; Estados UnidosFil: Devidas, Meenakshi. St Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. UCL Great Ormond Street Institute of Child Health; Reino UnidoFil: Rodriguez Galindo, Carlos. St Jude Children's Research Hospital; Estados Unido

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Hospitalisation for cancer and co-morbidities among people with learning disability in Australia

In Australia, general health and medical services are subsidised by the government. This includes care for people with disabilities, screening and diagnostic services for common diseases, including cancer, and care and treatment for various medical conditions. In Western Australia, the majority of state-provided health services are well documented in linkable databases. We have examined data from a large cohort of people receiving services for learning disability from the state and linked this with the state cancer registry and hospital records. While people with learning disability appear to be at similar risk for cancer, they may have poorer treatment outcomes as they already experience a range of health conditions which can exacerbate medical complications associated with treatment and/or other primary or secondary co-morbid conditions. Our results show that the mean number of hospital admissions were higher for the cancer group, even when adjustments were made for conditions such as childhood leukaemia and renal dialysis both of which often require frequent hospitalisations. Multivariate regression analyses showed that younger age, female sex and severe or unspecified level of disability were significant contributors to the frequency of hospital admissions. Qualitative information gleaned from detailed chart reviews showed that in addition to considerable morbidity, some patients were admitted repeatedly either because of lack of supportive environments and/or lack of compliance with treatment. Issues in providing appropriate support services for individuals and their carers are discussed

The test-negative design for estimating influenza vaccination effectiveness

ObjectiveWe aimed to describe the theoretical basis and the potentialapplications of the test-negative design for estimating influenzavaccination effectiveness in sentinel influenza surveillance.IntroductionThe test-negative design is a variation of the case-control study,in which patients are enrolled in outpatient clinics (and/or hospitals)based on a clinical case definition such as influenza-like illness (ILI).Patients are then tested for influenza virus, and VE is estimated fromthe odds ratio comparing the odds of vaccination among patientstesting positive for influenza versus those testing negative, adjustingfor potential confounding factors. The design leverages existingdisease surveillance networks and as a result, studies using it areincreasingly being reported.MethodsWe sought to examine the theoretical basis for this design usingcausal analysis including directed acyclic graphs. We reviewedstudies that used this design and examined the study populations andsettings, the methodologic choices including analytic approaches, andthe estimates of influenza VE provided. We conducted simulationstudies to examine specific potential biases.ResultsWe show how studies using this design can avoid or minimizebias, and where bias may be introduced with particular study designvariations. A purported advantage of the test-negative designis to minimise selection bias by health-care seeking behaviourand we demonstrate why residual bias may occur. Anotherpurported advantage of the test-negative design is minimization ofmisclassification of the exposure; however we show how this sourceof bias may persist and how exposure misclassification may bea greater cause for concern not dealt with by the study design. Inour review, we found great variation in estimates, but consistencybetween interim and final VE estimates from the same locations,and consistency between VE estimates from inpatient and outpatientstudies in the same locations, age groups and years. One outstandingissue is the potential bias due to non-collapsibility.ConclusionsOur work provides a starting point for further consideration of thevalidity of the test-negative design, which is an efficient approachfor routine monitoring of influenza VE that can be implemented inexisting surveillance systems without substantial additional resources.Harmonization of analytic approaches may improve the potential forpooling VE estimates

The test-negative design for estimating influenza vaccination effectiveness

ObjectiveWe aimed to describe the theoretical basis and the potentialapplications of the test-negative design for estimating influenzavaccination effectiveness in sentinel influenza surveillance.IntroductionThe test-negative design is a variation of the case-control study,in which patients are enrolled in outpatient clinics (and/or hospitals)based on a clinical case definition such as influenza-like illness (ILI).Patients are then tested for influenza virus, and VE is estimated fromthe odds ratio comparing the odds of vaccination among patientstesting positive for influenza versus those testing negative, adjustingfor potential confounding factors. The design leverages existingdisease surveillance networks and as a result, studies using it areincreasingly being reported.MethodsWe sought to examine the theoretical basis for this design usingcausal analysis including directed acyclic graphs. We reviewedstudies that used this design and examined the study populations andsettings, the methodologic choices including analytic approaches, andthe estimates of influenza VE provided. We conducted simulationstudies to examine specific potential biases.ResultsWe show how studies using this design can avoid or minimizebias, and where bias may be introduced with particular study designvariations. A purported advantage of the test-negative designis to minimise selection bias by health-care seeking behaviourand we demonstrate why residual bias may occur. Anotherpurported advantage of the test-negative design is minimization ofmisclassification of the exposure; however we show how this sourceof bias may persist and how exposure misclassification may bea greater cause for concern not dealt with by the study design. Inour review, we found great variation in estimates, but consistencybetween interim and final VE estimates from the same locations,and consistency between VE estimates from inpatient and outpatientstudies in the same locations, age groups and years. One outstandingissue is the potential bias due to non-collapsibility.ConclusionsOur work provides a starting point for further consideration of thevalidity of the test-negative design, which is an efficient approachfor routine monitoring of influenza VE that can be implemented inexisting surveillance systems without substantial additional resources.Harmonization of analytic approaches may improve the potential forpooling VE estimates