COVID-19 Vaccine Effectiveness Among Adolescents.

BACKGROUND: For adolescents, data on the long-term effectiveness of the BNT162b2 and mRNA-1273 vaccines against severe COVID-19 outcomes are scarce. Additionally, only a few studies have evaluated vaccine effectiveness (VE) for mRNA-1273 or heterologous mRNA vaccine schedules (ie, mixing BNT162b2 and mRNA-1273). METHODS: Nationwide register-based 1-to-1 matched cohort analyses were conducted in Denmark, Finland, Norway, and Sweden between May 28, 2021, and April 30, 2023, to estimate VE for primary COVID-19 vaccine (2-dose) schedules among adolescents aged 12 to 17 years. Cumulative incidences of COVID-19-related hospitalization (primary outcome) and laboratory-confirmed SARS-CoV-2 infection (secondary outcome) were compared for vaccinated and unvaccinated at 6 months of follow-up using the Kaplan-Meier estimator. Country-specific VE (1-risk ratio) and risk differences (RD) were combined by random-effects meta-analyses. RESULTS: The study included 526 966 primary schedule vaccinated adolescents. VE against COVID-19-related hospitalization was 72.6% (95% confidence interval [CI], 62.5-82.7) and RD was -2.8 (95% CI, -4.5 to -1.0) per 10 000 vaccinated for BNT162b2 at 6 months of follow-up compared with unvaccinated. The corresponding VE and RD were 86.0% (95% CI, 56.8-100.0) and -2.1 (95% CI, -4.0 to -0.2) per 10 000 vaccinated for mRNA-1273 and 80.7% (95% CI, 58.0-100.0) and -5.5 (95% CI, -15.5 to 4.6) per 10 000 vaccinated for heterologous mRNA vaccine schedules. Estimates were comparable when restricting to a period of omicron predominance and extending follow-up to 12 months. CONCLUSIONS: Across 4 Nordic countries, severe COVID-19 in adolescents was a rare event. Compared with unvaccinated, BNT162b2, mRNA-1273, and heterologous mRNA vaccination schedules provided high protection against COVID-19-related hospitalization, including hospitalizations during the omicron period.

Effectiveness of Vaccines and Monoclonal Antibodies Against Respiratory Syncytial Virus: Generic Protocol for Register-Based Cohort Study.

Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site.

Brand-specific estimates of influenza vaccine effectiveness for the 2021-2022 season in Europe: results from the DRIVE multi-stakeholder study platform.

Introduction: Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022. Methods: In 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis. Results: In 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting). Discussion: Over five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses.

OBJECTIVE: To investigate the comparative vaccine effectiveness of heterologous booster schedules (ie, three vaccine doses) compared with primary schedules (two vaccine doses) and with homologous mRNA vaccine booster schedules (three vaccine doses) during a period of omicron predominance. DESIGN: Population based cohort analyses. SETTING: Denmark, Finland, Norway, and Sweden, 27 December 2020 to 31 December 2022. PARTICIPANTS: All adults aged ≥18 years who had received at least a primary vaccination schedule of AZD1222 (Oxford-AstraZeneca) or monovalent SARS-CoV-2 wild type (ancestral) strain based mRNA vaccines BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), in any combination. MAIN OUTCOME MEASURES: The main outcome measure was country combined risks of covid-19 related hospital admission and death with covid-19 and additional outcomes of covid-19 related admission to an intensive care unit and SARS-CoV-2 infection. During a period of omicron predominance, these outcomes were compared in those who received a heterologous booster versus primary schedule (matched analyses) and versus those who received a homologous mRNA vaccine booster (weighted analyses). Follow-up was for 75 days from day 14 after the booster dose; comparative vaccine effectiveness was calculated as 1-risk ratio. RESULTS: Across the four Nordic countries, 1 086 418 participants had received a heterologous booster schedule of AZD1222+BNT162b2 or mRNA-1273 and 2 505 093 had received a heterologous booster schedule of BNT162b2+mRNA-1273. Compared with the primary schedule only (two doses), the vaccine effectiveness of heterologous booster schedules comprising AZD1222+BNT162b2 or mRNA-1273 and BNT162b2+mRNA-1273 was 82.7% (95% confidence interval 77.1% to 88.2%) and 81.5% (78.9% to 84.2%) for covid-19 related hospital admission and 95.9% (91.6% to 100.0%) and 87.5% (82.5% to 92.6%) for death with covid-19, respectively. Homologous mRNA booster schedules were similarly associated with increased protection against covid-19 related hospital admission (≥76.5%) and death with covid-19 (≥84.1%) compared with previous primary course vaccination only. When a heterologous booster schedule was compared with the homologous booster schedule, vaccine effectiveness was 27.2% (3.7% to 50.6%) for AZD1222+BNT162b2 or mRNA-1273 and 23.3% (15.8% to 30.8%) for BNT162b2+mRNA-1273 schedules against covid-19 related hospital admission and 21.7% (-8.3% to 51.7%) and 18.4% (-15.7% to 52.5%) against death with covid-19, respectively. CONCLUSION: Heterologous booster schedules are associated with increased protection against severe, omicron related covid-19 outcomes compared with primary course schedules and homologous booster schedules.

Comparative effectiveness of bivalent BA.4-5 and BA.1 mRNA booster vaccines among adults aged ≥50 years in Nordic countries: nationwide cohort study.

OBJECTIVE: To estimate the effectiveness of the bivalent mRNA booster vaccines containing the original SARS-CoV-2 and omicron BA.4-5 or BA.1 subvariants as the fourth dose against severe covid-19. DESIGN: Nationwide cohort analyses, using target trial emulation. SETTING: Denmark, Finland, Norway, and Sweden, from 1 July 2022 to 10 April 2023. PARTICIPANTS: People aged ≥50 years who had received at least three doses of covid-19 vaccine (that is, a primary course and a first booster). MAIN OUTCOME MEASURES: The Kaplan-Meier estimator was used to compare the risk of hospital admission and death related to covid-19 in people who received a bivalent Comirnaty (Pfizer-BioNTech) or Spikevax (Moderna) BA.4-5 or BA.1 mRNA booster vaccine as a fourth dose (second booster) with three dose (first booster) vaccinated people and between four dose vaccinated people. RESULTS: A total of 1 634 199 people receiving bivalent BA.4-5 fourth dose booster and 1 042 124 receiving bivalent BA.1 fourth dose booster across the four Nordic countries were included. Receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a comparative vaccine effectiveness against admission to hospital with covid-19 of 67.8% (95% confidence interval 63.1% to 72.5%) and a risk difference of -91.9 (95% confidence interval -152.4 to -31.4) per 100 000 people at three months of follow-up compared with having received three doses of vaccine (289 v 893 events). The corresponding comparative vaccine effectiveness and risk difference for bivalent BA.1 boosters (332 v 977 events) were 65.8% (59.1% to 72.4%) and -112.9 (-179.6 to -46.2) per 100 000, respectively. Comparative vaccine effectiveness and risk difference against covid-19 related death were 69.8% (52.8% to 86.8%) and -34.1 (-40.1 to -28.2) per 100 000 for bivalent BA.4-5 booster (93 v 325 events) and 70.0% (50.3% to 89.7%) and -38.7 (-65.4 to -12.0) per 100 000 for BA.1 booster (86 v 286) as a fourth dose. Comparing bivalent BA.4-5 and BA.1 boosters as a fourth dose directly resulted in a three month comparative vaccine effectiveness and corresponding risk difference of -14.9% (-62.3% to 32.4%) and 10.0 (-14.4 to 34.4) per 100 000 people for admission to hospital with covid-19 (802 v 932 unweighted events) and -40.7% (-123.4% to 42.1%) and 8.1 (-3.3 to 19.4) per 100 000 for covid-19 related death (229 v 243 unweighted events). The comparative vaccine effectiveness did not differ across sex and age (

High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron.

BACKGROUND: The elderly are highly vulnerable to severe COVID-19. Waning immunity and emergence of Omicron have caused concerns about reduced effectiveness of COVID-19 vaccines. The objective was to estimate vaccine effectiveness (VE) against severe COVID-19 among the elderly. METHODS: This nationwide, register-based cohort analysis included all residents aged 70 years and over in Finland. The follow-up started on December 27, 2020, and ended on March 31, 2022. The outcomes of interest were COVID-19-related hospitalization and intensive care unit (ICU) admission timely associated with SARS-CoV-2 infection. VE was estimated as one minus the hazard ratio comparing the vaccinated and unvaccinated and taking into account time since vaccination. Omicron-specific VE was evaluated as the effectiveness observed since January 1, 2022. RESULTS: The cohort included 896,220 individuals. Comirnaty (BioNTech/Pfizer) VE against COVID-19-related hospitalization was 93% (95% CI 89-95%) and 85% (95% CI 82-87%) 14-90 and 91-180 days after the second dose; VE increased to 95% (95% CI 94-96%) 14-60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe COVID-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 98% (95% CI 92-99%) and 92% (95% CI 87-95%) 14-90 and 91-180 days after the second and 98% (95% CI 95-99%) 14-60 days after the third dose. CONCLUSIONS: VE against severe COVID-19 is high among the elderly. It waned slightly after two doses, but a third restored the protection. VE against severe COVID-19 remained high even after the emergence of Omicron.

Neurological Outpatients Prefer EEG Home-Monitoring over Inpatient Monitoring-An Analysis Based on the UTAUT Model.

Home monitoring examinations offer diagnostic and economic advantages compared to inpatient monitoring. In addition, these technical solutions support the preservation of health care in rural areas in the absence of local care providers. The acceptance of patients is crucial for the implementation of home monitoring concepts. The present research assesses the preference for a health service that is to be introduced, namely an EEG home-monitoring of neurological outpatients-using a mobile, dry-electrode EEG (electroencephalography) system-in comparison to the traditional long-time EEG examination in a hospital. Results of a representative study for Germany (n = 421) reveal a preference for home monitoring. Importantly, this preference is partially driven by a video explaining the home monitoring system. We subsequently analyzed factors that influence the behavioral intention (BI) to use the new EEG system, drawing on an extended Unified Theory of Acceptance and Use of Technology (UTAUT) model. The strongest positive predictor of BI is the belief that EEG home-monitoring will improve health quality, while computer anxiety and effort expectancy represent the strongest barriers. Furthermore, we find the UTAUT model's behavioral intention construct to predict the patients' decision for or against home monitoring more strongly than any other patient's characteristic such as gender, health condition, or age, underlying the model's usefulness.

Effectiveness of trivalent influenza vaccines against hospitalizations due to laboratory-confirmed influenza a in the elderly: Comparison of test-negative design with register-based designs.

INTRODUCTION: Measuring influenza vaccine effectiveness (IVE) seasonally is important and has been conducted utilizing several observational study designs. The active test-negative design has been most widely used and the validity of passive register-based studies has been debated. We aimed to explore the potential differences, advantages, and weaknesses of different study designs in estimating influenza vaccine effectiveness. METHODS: We compared three study designs in estimating IVE against hospitalization in the elderly aged 65 years or more over three influenza seasons 2015/16, 2016/17 and 2017/18. Designs compared were active test-negative design (TND), register-based cohort design and register-based case-control design with different selection criteria for cases and controls. RESULTS: Adjusted IVE estimates for the three consecutive seasons 2015-18 in active test-negative design were 82% (95% confidence interval 26, 96), 21% (-179, 77), 15% (-113, 66). For case-control design, estimates from different analyses ranged in 2015/16 from 47% (-16, 76) to 52% (-48, 84), in 2016/17 from 10% (-42, 43) to 29% (-20, 58), and in 2017/18 from -27% (-91, 15) to 1% (-40, 30). In the cohort design, the adjusted IVE estimates were 48% (-9, 75), 29% (1, 49), 13% (-21, 37) for the three seasons. CONCLUSIONS: The register-based cohort design produced results more concordant with the active test-negative design than the case-control design. Furthermore, the register-based cohort design yielded most precise estimates with narrower confidence intervals. In Finland with the availability of near real-time nationwide register data, the register-based cohort design is the method of choice to continue the annual surveillance of influenza vaccine effectiveness.

Feasibility assessment of patient-controlled EEG home-monitoring: More results from the HOMEONE study.

OBJECTIVE: The feasibility phase of the HOME (Home-Monitoing and Education) project aims to show the practical feasibility of Electroencephalography (EEG)home-monitoring using a patient-controlled mobile system. Its objective is to assess the potential diagnostic and therapeutic yields of home-monitoring compared to conventional healthcare. METHODS: 16 office-based practitioners chose 97 patients and recorded standard 20-minute EEGs using conventional recorders. After training, the same patients used a patient-controlled mobile dry electrode EEG system in their home environment. The practitioners in charge and two additional raters assessed all recordings. We conducted inter-rater and intra-rater comparisons between the diagnostic findings. RESULTS: 89 patients successfully conducted home-monitoring recordings. The intra-rater comparison results for the diagnostic findings of the conventional recordings and the patient-made recordings show a fair Cohen's kappa value (0.21). Additionally, we documented a change of patient management in 9 cases. CONCLUSIONS: The feasibility of EEG home-monitoring using a patient-controlled device is confirmed. The yield of EEG home-monitoring comprises information that can influence patient management. SIGNIFICANCE: Patient-controlled EEG home-monitoring is feasible as part of routine care for neurological outpatients as its technical efficacy and practical feasibility are shown and significantly positive effects on patient management are evidenced.

Predictors of hospitalisation and death due to SARS-CoV-2 infection in Finland: A population-based register study with implications to vaccinations.

INTRODUCTION: The aim of this study was to investigate how age and underlying medical conditions affect the risk of severe outcomes following SARS-CoV-2 infection and how they should be weighed while prioritising vaccinations against COVID-19. METHODS: This population-based register study includes all SARS-CoV-2 PCR-test-positive cases until 24 Feb 2021, based on the Finnish National Infectious Diseases Register. The cases were linked to other registers to identify presence of predisposing factors and severe outcomes (hospitalisation, intensive care treatment, death). The odds of severe outcomes were compared in those with and without the pre-specified predisposing factors using logistic regression. Furthermore, population-based rates were compared between those with a given predisposing factor and those without any of the specified predisposing factors using negative binomial regression. RESULTS: Age and various comorbidities were found to be predictors of severe COVID-19. Compared to 60-69-year-olds, the odds ratio (OR) of death was 7.1 for 70-79-year-olds, 26.7 for 80-89-year-olds, and 55.8 for ≥ 90-year-olds. Among the 20-69-year-olds, chronic renal disease (OR 9.4), malignant neoplasms (5.8), hematologic malignancy (5.6), chronic pulmonary disease (5.4), and cerebral palsy or other paralytic syndromes (4.6) were strongly associated with COVID-19 mortality; severe disorders of the immune system (8.0), organ or stem cell transplant (7.2), chronic renal disease (6.7), and diseases of myoneural junction and muscle (5.5) were strongly associated with COVID-19 hospitalisation. Type 2 diabetes and asthma, two very common comorbidities, were associated with all three outcomes, with ORs from 2.1 to 4.3. The population-based rate of SARS-CoV-2 infection decreased with age. Taking the 60-69-year-olds as reference, the rate ratio was highest (3.0) for 20-29-year-olds and < 1 for 70-79-year-olds and 80-89-year-olds. CONCLUSION: Comorbidities predispose for severe COVID-19 among younger ages. In vaccine prioritisation both the risk of infection and the risk of severe outcomes, if infected, should be considered.

Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland, December 2020 - October 2021.

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79-85%) 14-90 days after vaccination to 53% (43-62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.

Effectiveness of vaccination against SARS-CoV-2 infection and Covid-19 hospitalisation among Finnish elderly and chronically ill-An interim analysis of a nationwide cohort study.

BACKGROUND: In Finland, both mRNA and adenovirus vector (AdV) Covid-19 vaccines have been used after the vaccination campaign started on December 27, 2020. Vaccination of the elderly and chronically ill was prioritized and the interval between doses set to 12 weeks. The objective of this interim analysis was to evaluate first and second dose vaccine effectiveness (VE) in a real-world setting. METHODS: During the first five months of the campaign, a register-based cohort study was conducted in the Finnish elderly aged 70+ years and those aged 16-69 years with medical conditions predisposing to severe Covid-19 (chronically ill). Using Cox regression, VE against SARS-CoV-2 infection and Covid-19 hospitalisation was estimated comparing the hazard in the vaccinated with that in the unvaccinated. RESULTS: The cohorts included 901092 elderly (89% vaccinated) and 774526 chronically ill (69% vaccinated) individuals. Three weeks after the first dose, mRNA VE against infection was 45% (95% confidence interval, 36-53%) and 40% (26-51%) in elderly and chronically ill; mRNA VE against hospitalisation was 63% (49-74%) and 82% (56-93%). In chronically ill, AdV VE was 42% (32-50) and 62% (42-75%) against infection and hospitalisation, respectively. One week after the second dose, mRNA VE against infection was 75% (65-82%) and 77% (65-85%) in elderly and chronically ill; mRNA VE against hospitalisation was 93% (70-98%) and 90% (29-99%). CONCLUSIONS: Covid-19 vaccines protect against SARS-CoV-2 infection and Covid-19 hospitalisation. A single dose provides moderate protection in elderly and chronically ill, although two doses are clearly superior.

Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes, Finland, 2012/13 to 2019/20.

BackgroundCohort studies on vaccine effectiveness are prone to confounding bias if the distribution of risk factors is unbalanced between vaccinated and unvaccinated study subjects.AimWe aimed to estimate influenza vaccine effectiveness in the elderly population in Finland by controlling for a sufficient set of confounders based on routinely available register data.MethodsFor each of the eight consecutive influenza seasons from 2012/13 through 2019/20, we conducted a cohort study comparing the hazards of laboratory-confirmed influenza in vaccinated and unvaccinated people aged 65-100 years using individual-level medical and demographic data. Vaccine effectiveness was estimated as 1 minus the hazard ratio adjusted for the confounders age, sex, vaccination history, nights hospitalised in the past and presence of underlying chronic conditions. To assess the adequacy of the selected set of confounders, we estimated hazard ratios of off-season hospitalisation for acute respiratory infection as a negative control outcome.ResultsEach analysed cohort comprised around 1 million subjects, of whom 37% to 49% were vaccinated. Vaccine effectiveness against laboratory-confirmed influenza ranged from 16% (95% confidence interval (CI): 12-19) to 48% (95% CI: 41-54). More than 80% of the laboratory-confirmed cases were hospitalised. The adjusted off-season hazard ratio estimates varied between 1.00 (95% CI: 0.94-1.05) and 1.08 (95% CI: 1.01-1.15), indicating that residual confounding was absent or negligible.ConclusionSeasonal influenza vaccination reduces the hazard of severe influenza disease in vaccinated elderly people. Data about age, sex, vaccination history and utilisation of hospital care proved sufficient to control confounding.

Exposure misclassification bias in the estimation of vaccine effectiveness.

In epidemiology, a typical measure of interest is the risk of disease conditional upon exposure. A common source of bias in the estimation of risks and risk ratios is misclassification. Exposure misclassification affects the measurement of exposure, i.e. the variable one conditions on. This article explains how to assess biases under non-differential exposure misclassification when estimating vaccine effectiveness, i.e. the vaccine-induced relative reduction in the risk of disease. The problem can be described in terms of three binary variables: the unobserved true exposure status, the observed but potentially misclassified exposure status, and the observed true disease status. The bias due to exposure misclassification is quantified by the difference between the naïve estimand defined as one minus the risk ratio comparing individuals observed as vaccinated with individuals observed as unvaccinated, and the vaccine effectiveness defined as one minus the risk ratio comparing truly vaccinated with truly unvaccinated. The magnitude of the bias depends on five factors: the risks of disease in the truly vaccinated and the truly unvaccinated, the sensitivity and specificity of exposure measurement, and vaccination coverage. Non-differential exposure misclassification bias is always negative. In practice, if the sensitivity and specificity are known or estimable from external sources, the true risks and the vaccination coverage can be estimated from the observed data and, thus, the estimation of vaccine effectiveness based on the observed risks can be corrected for exposure misclassification. When analysing risks under misclassification, careful consideration of conditional probabilities is crucial.

Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes-applications to influenza vaccine effectiveness.

BACKGROUND: Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios. METHODS: Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data. RESULTS: The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small. CONCLUSIONS: The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.

Effectiveness of 2 Influenza Vaccines in Nationwide Cohorts of Finnish 2-Year-Old Children in the Seasons 2015-2016 Through 2017-2018.

BACKGROUND: From 2015-2016 through 2017-2018, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in 2-year-olds was estimated for all 3 seasons. METHODS: Each season, a nationwide register-based cohort study was conducted. The study population comprised 60 088, 60 860, and 60 345 children in 2015-2016, 2016-2017, and 2017-2018, respectively. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS: From 2015-2016 through 2017-2018, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2-69.0%), 20.3% (-12.7%, 43.6%), and 30.5% (10.9-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9-89.8%), 24.5% (-29.8%, 56.1%), and -20.1% (-61.5%, 10.7%). Neither influenza vaccine clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS: To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates also expressing overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

Cohort study design for estimating the effectiveness of seasonal influenza vaccines in real time based on register data: The Finnish example.

This paper presents the principles of implementing register-based cohort studies as currently applied for real-time estimation of influenza vaccine effectiveness in Finland. All required information is retrieved from computerised national registers and deterministically linked via the unique personal identity code assigned to each Finnish resident. The study cohorts comprise large subpopulations eligible for a free seasonal influenza vaccination as part of the National Vaccination Programme. The primary outcome is laboratory-confirmed influenza. Each study subject is taken to be at risk of experiencing the outcome from the onset of the influenza season until the first of the following three events occurs: outcome, loss to follow up or end of season. Seasonal influenza vaccination is viewed as time-dependent exposure. Accordingly, each subject may contribute unvaccinated and vaccinated person-time during their time at risk. The vaccine effectiveness is estimated as one minus the influenza incidence rate ratio comparing the vaccinated with the unvaccinated within the study cohorts. Data collection in register-based research is an almost fully automated process. The effort, resources and the time spent in the field are relatively small compared to other observational study designs. This advantage is pivotal when vaccine effectiveness estimates are needed in real time. The paper outlines possible limitations of register-based cohort studies. It also addresses the need to explore how national and subnational registers available in the Nordic countries and elsewhere can be utilised in vaccine effectiveness research to guide decision making and to improve individual health as well as public health.

Organisation of preventive child health services: Key to socio-economic equity in vaccine uptake?

Background: Measles has made a comeback in Western Europe, with more cases being reported each year. One factor behind this development is low vaccination coverage in socially disadvantaged segments of the population in many countries. This study investigates whether socioeconomic patterns of uptake of the measles, mumps and rubella (MMR) vaccine in the Nordic countries differ by national organisation of preventive health services for children. Methods: MMR vaccine uptake before the age of two years was analysed in register data from Denmark, Finland, Iceland and Sweden, linked to family indicators of socio-economic status (SES) from national registers. Results: Denmark, a country where child vaccinations are administered by general practitioners, presented the lowest overall coverage of MMR at 83%. It also had the greatest difference between subpopulations of low and high SES at 14 percentage points. Finland, Iceland and Sweden, countries where preschool children are vaccinated in 'well-baby' clinics, had a higher overall coverage at 91-94%, with a more equal distribution between SES groups at 1-4 percentage points. Conclusions: This study suggests that the organisation of preventive health care in special units, 'well-baby' clinics, facilitates vaccine uptake among children with low SES in a Nordic welfare context.