Uncovering the burden of Influenza in children in Portugal, 2008-2018.

BACKGROUND: Despite their higher risk of developing severe disease, little is known about the burden of influenza in Portugal in children aged < 5 years old. This study aims to cover this gap by estimating the clinical and economic burden of severe influenza in children, in Portugal, during ten consecutive influenza seasons (2008/09-2017/18). METHODS: We reviewed hospitalizations in children aged < 5 years old using anonymized administrative data covering all public hospitals discharges in mainland Portugal. The burden of hospitalization and in-hospital mortality directly coded as due to influenza was supplemented by the indirect burden calculated from excess hospitalization and mortality (influenza-associated), estimated for four groups of diagnoses (pneumonia or influenza, respiratory, respiratory or cardiovascular, and all-cause), through cyclic regression models integrating the incidence of influenza. Means were reported excluding the H1N1pdm09 pandemic (2009/10). RESULTS: The mean annual number of hospitalizations coded as due to influenza was 189 (41.3 cases per 100,000 children aged < 5 years old). Hospitalization rates decreased with increasing age. Nine-in-ten children were previously healthy, but the presence of comorbidities increased with age. Children stayed, on average, 6.1 days at the hospital. Invasive mechanical ventilation was used in 2.4% of hospitalizations and non-invasive in 3.1%. Influenza-associated excess hospitalizations between 2008 and 2018 were estimated at 1,850 in pneumonia or influenza, 1,760 in respiratory, 1,787 in respiratory or cardiovascular, and 1,879 in all-cause models. A total of 95 influenza-associated excess deaths were estimated in all-cause, 14 in respiratory or cardiovascular, and 9 in respiratory models. Over ten years, influenza hospitalizations were estimated to have cost the National Health Service at least €2.9 million, of which 66.5% from healthy children. CONCLUSIONS: Influenza viruses led to a high number of hospitalizations in children. Most were previously healthy. Results should lead to a reflection on the adequate preventive measures to protect this age group.

Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives.

BACKGROUND: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK. METHODS: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs. RESULTS: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France. CONCLUSIONS: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits.

The impact of clinical risk conditions on influenza and pneumonia diagnoses in England: a nationally representative retrospective cohort study, 2010-2019.

The impact of influenza and pneumonia on individuals in clinical risk groups in England has not previously been well characterized. Using nationally representative linked databases (Clinical Practice Research Database (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS)), we conducted a retrospective cohort study among adults (≥ 18 years) during the 2010/2011-2019/2020 influenza seasons to estimate the incidence of influenza- and pneumonia-diagnosed medical events (general practitioner (GP) diagnoses, hospitalisations and deaths), stratified by age and risk conditions. The study population included a seasonal average of 7.2 million individuals; approximately 32% had ≥1 risk condition, 42% of whom received seasonal influenza vaccines. Medical event incidence rates increased with age, with ~1% of adults aged ≥75 years hospitalized for influenza/pneumonia annually. Among individuals with vs. without risk conditions, GP diagnoses occurred 2-5-fold more frequently and hospitalisations were 7-10-fold more common. Among those with obesity, respiratory, kidney or cardiovascular disorders, hospitalisation were 5-40-fold more common than in individuals with no risk conditions. Though these findings likely underestimate the full burden of influenza, they emphasize the concentration of disease burden in specific age and risk groups and support existing recommendations for influenza vaccination.

Excess hospitalizations and mortality associated with seasonal influenza in Portugal, 2008-2018.

BACKGROUND: Influenza can have a domino effect, triggering severe conditions and leading to hospitalization or even death. Since influenza testing is not routinely performed, statistical modeling techniques are increasingly being used to estimate annual hospitalizations and deaths associated with influenza, to overcome the known underestimation from registers coded with influenza-specific diagnosis. The aim of this study was to estimate the clinical and economic burden of severe influenza in Portugal. METHODS: The study comprised ten epidemic seasons (2008/09-2017/18) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization incidence, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487-488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480-488, 517.1; ICD-10: J09-J18), respiratory (ICD-9: 460-519; ICD-10: J00-J99), respiratory or cardiovascular (R&C, ICD-9: 390-459, 460-519; ICD-10: I00-I99, J00-J99), and all-cause. Means are reported excluding the H1N1pdm09 pandemic (2009/10). RESULTS: The mean number of hospitalizations coded as due to influenza per season was 1,207, resulting in 11.6 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €3.9 million, of which 78.6% was generated by patients with comorbidities. Mean annual influenza-associated R&C hospitalizations were estimated at 5356 (min: 456; max: 8776), corresponding to 51.5 cases per 100,000 (95% CI: 40.9-62.0) for all age groups and 199.6 (95% CI: 163.9-235.8) for the population aged ≥ 65 years. The mean direct annual cost of the estimated excess R&C hospitalizations was €15.2 million for all age groups and €12.8 million for the population aged ≥ 65 years. Mean annual influenza-associated all-cause deaths per 100,000 people were estimated at 22.7 for all age groups. CONCLUSIONS: The study findings suggest that there is an under-detection of influenza in the Portuguese population. A high burden of severe influenza remains to be addressed, not only in the elderly population but also in younger people.

Epidemiology of invasive meningococcal disease and sequelae in the United Kingdom during the period 2008 to 2017 - a secondary database analysis.

BACKGROUND: Invasive meningococcal disease (IMD) causes high fatality in untreated patients alongside long-term sequelae in 20% survivors. For a comprehensive assessment of epidemiology, an analysis of these sequelae is required. This study aims to investigate the epidemiology of disease between 2008 and 2017 including a description of the sequelae, through the analysis of data collected from the UK Clinical Practice Research Datalink (CPRD) linked with data from the Hospital Episode Statistics (HES), and Office for National Statistics (ONS) mortality registry data. METHODS: This was a 10-year retrospective observational cohort study designed to describe the incidence, case-fatality rate (CFR) and occurrence of sequelae due to meningococcal disease, in the UK between 2007 and 2017 using data from the UK CPRD-HES-ONS. Cases were identified and matched on age, gender, date of diagnosis of IMD and followed-up-time with a control group without IMD. Demographics, clinical characteristics, mortality, and IMD-related sequelae were examined for IMD cases and compared with matched controls for a more comprehensive assessment. RESULTS: The study analysed 640 IMD patients with majority of the cases diagnosed (76.9%) in a hospital setting. Age-group analysis showed a decrease in the incidence rate of IMD in patients aged <1 year (30.4 - 7.5%) and an increase in those >50 years (10.4 - 27.8%). CFR was slightly higher among females, toddlers, and adults >50 years. No significant change in CFR was observed over study period. Case-control study showed a higher number of IMD sequelae among cases compared to age- and gender-matched controls, especially in those ≥ 50 years. CONCLUSION: The study showed that, despite a relatively low incidence rate, IMD is responsible for a high CFR, namely in older age groups and by a high number of IMD sequelae. The study showed that leveraging data from existing databases can be used to complement surveillance data in truly assessing the epidemiology of IMD. Despite the availability of routine vaccination programs, IMD still poses a significant burden in the healthcare system of the UK. Optimization of vaccination programs may be required to reduce the disease burden.

Clinical and economic burden of physician-diagnosed influenza in adults during the 2017/2018 epidemic season in Spain.

BACKGROUND: Influenza is an acutely debilitating respiratory infection, contributing significantly to outpatient visits and hospitalizations. Spain lacks comprehensive and updated data on the burden of influenza, particularly in the outpatient setting. Our study aimed to fill this gap by estimating the clinical and economic burden of physician-diagnosed influenza cases in adults from four Spanish regions, stratified by age groups and presence of comorbidities. METHODS: A retrospective cost-of-illness study was conducted using data from an electronic medical records database from the National Healthcare Service (NHS) of four Spanish regions for individuals aged ≥ 18 years diagnosed for influenza during the 2017/2018 epidemic season. Health resource utilization and related cost data were collected, including primary care visits, referrals to other specialists, visits to the emergency department, hospitalizations, and prescribed medicines. RESULTS: The study reported a total of 28,381 patients aged ≥ 18 years diagnosed with influenza, corresponding to 1,804 cases per 100,000 population. Most patients were aged < 65 years: 60.5% (n = 17,166) aged 18-49 and 26.3% (n = 7,451) 50-64 years. A total of 39.2% (n = 11,132) of patients presented a comorbidity. Cardiovascular diseases were the most common comorbidity reported along with influenza. The mean healthcare cost per case was estimated at €235.1 in population aged 18-49 years, increasing by 1.7 and 4.9 times in those aged 50-64 (€402.0) and ≥ 65 (€1,149.0), respectively. The mean healthcare cost per case was 3.2 times higher in patients with comorbidities. The total healthcare cost of medically attended influenza cases was mainly driven by primary care (45.1%) and hospitalization (42.0%). Patients aged 18-64 years old accounted for 61.9% of the costs of medically attended influenza. Irrespective of age, patients with comorbidities accounted for 67.1% of costs. CONCLUSIONS: Season 2017/2018 was associated with a considerable burden of influenza in Spain, which increased with age and presence of comorbidities. Individuals with comorbidities accounted for most of the costs of influenza. Results suggest that population aged 18-64 years old is generating the highest share of costs to the NHS when all healthcare costs are considered. Preventive strategies targeting subjects with comorbidities, regardless of age, should be warranted.

National influenza surveillance systems in five European countries: a qualitative comparative framework based on WHO guidance.

BACKGROUND: Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance. METHODS: Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries. RESULTS: France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data. CONCLUSIONS: This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases.

Compared characteristics of current vs. past smokers at the time of diagnosis of a first-time lung or head and neck cancer: a cross-sectional study.

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.

Passive enhanced safety surveillance for Vaxigrip and Intanza 15 µg in the United Kingdom and Finland during the northern hemisphere influenza season 2015/16.

Enhanced safety surveillance (ESS) was conducted in the United Kingdom and Finland for Vaxigrip and Intanza 15 µg to comply with the European Medicines Agency interim guidance aimed to detect any potential increase in reactogenicity in near real time following the annual update of the influenza vaccine strain composition. This pilot passive ESS was established to strengthen safety monitoring by facilitating spontaneous vaccinee reports and estimating near real-time vaccinee exposure. The primary objective was to estimate the reporting rates of suspected adverse reactions (ARs) occurring within 7 days post vaccination during the northern hemisphere 2015/16 influenza season. Among the Vaxigrip vaccinees (n = 1,012), 32 (3.2%) reported a total of 122 suspected ARs, including 110 suspected ARs that occurred within 7 days post vaccination. Among the Intanza 15 µg vaccinees (n = 1,017), 31 (3.0%) reported a total of 114 suspected ARs, including 99 that occurred within 7 days post-vaccination. These results were consistent with the known safety profile of the two vaccines and did not show any change in reactogenicity or safety concerns. This passive ESS showed improved data reporting and demonstrated its suitability to health authorities' requirements; further fine tuning of the methodology is under discussion between all stakeholders.

Herpes zoster-associated mortality in Europe: a systematic review.

BACKGROUND: Reactivation of latent varicella zoster virus, partly due to age-related immunosenescence and immunosuppressive conditions, results in herpes zoster (HZ) and its associated complications. The management of the most important complication, post-herpetic neuralgia (PHN), is challenging, particularly in the elderly, and is generally unsatisfactory. No previous reviews have reported the incidence of HZ-associated mortality. METHODS: We carried out a systematic literature review to identify studies and databases providing data for HZ-associated mortality in adults aged ≥ 50 years in Europe. RESULTS: We identified 12 studies: Belgium (1); France (1); Germany (1); the Netherlands (2); Portugal (1); Spain (4) and England/Wales (2) and 4 databases from Europe: France; Germany and England/Wales. The incidence was available from eight studies; it was highest in those aged ≥ 95 in France (19.48/100,000). In the European (WHO) database, the overall mortality ranged from 0 to > 0.07/100,000. The age- and gender-specific HZ mortality rates from the other databases showed that while in younger age groups the HZ mortality rate was higher in males, in older patients the rate was much higher in women. The case fatality rate was 2 and 61/100,000 in those 45-65 and ≥ 65 years, respectively. A similar increase with age was seen for the hospital fatality rate; 0.6% in those 45-65 years in the UK and 7.1% in those ≥ 80 in Spain. CONCLUSIONS: Although the data were sparse and heterogeneous, HZ-associated mortality clearly increases with age. In addition, the elderly who develop HZ often have underlying diseases and are at increased risk of functional decline and loss of independence. Mortality should be taken into account in health-economics models.

Burden of herpes zoster-associated chronic pain in Italian patients aged 50 years and over (2009-2010): a GP-based prospective cohort study.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication in herpes zoster (HZ) patients. METHODS: We performed a longitudinal, prospective study in 108 general practices throughout Italy to assess how many immunocompetent patients aged ≥50 years with newly diagnosed HZ develop HZ-associated pain, its duration and management over 6-months. HZ-associated pain was assessed by a direct question to the patient and by self-assessment of the worst pain felt in the previous two weeks on a visual analogue scale (VAS), a score ≥3 was taken as pain. PHN was defined as pain reported during the study period persisting for ≥3 months. Quality of life (QoL) was measured using the SF-12 questionnaire. RESULTS: At enrolment, 370 of the 413 patients (89.6%) reported HZ-associated pain which was still present in 20.6% and 9.2% of patients after three and six months, respectively, despite many patients receiving recommended anti-viral therapy. The overall QoL scores were lower than those in healthy Italians of similar age; scores for patients with HZ-associated pain were lower. The presence of >50 vesicles and VAS score ≥3 at enrolment, and being male were significantly associated with PHN at three months. CONCLUSIONS: These results suggest that HZ and PHN represent an important burden of disease in the elderly. There is a need for interventions that can prevent and reduce the burden of HZ to help improve the quality of life of the elderly. These data may be useful as baseline epidemiology data for the assessment of the impact of the VZV vaccine in Italy, after its implementation.

Similar herpes zoster incidence across Europe: results from a systematic literature review.

BACKGROUND: Herpes zoster (HZ) is caused by reactivation of the varicella-zoster virus (VZV) and mainly affects individuals aged ≥50 years. The forthcoming European launch of a vaccine against HZ (Zostavax®) prompts the need for a better understanding of the epidemiology of HZ in Europe. Therefore the aim of this systematic review was to summarize the available data on HZ incidence in Europe and to describe age-specific incidence. METHODS: The Medline database of the National Library of Medicine was used to conduct a comprehensive literature search of population-based studies of HZ incidence published between 1960 and 2010 carried out in the 27 member countries of the European Union, Iceland, Norway and Switzerland. The identified articles were reviewed and scored according to a reading grid including various quality criteria, and HZ incidence data were extracted and presented by country. RESULTS: The search identified 21 studies, and revealed a similar annual HZ incidence throughout Europe, varying by country from 2.0 to 4.6/1 000 person-years with no clearly observed geographic trend. Despite the fact that age groups differed from one study to another, age-specific HZ incidence rates seemed to hold steady during the review period, at around 1/1 000 children <10 years, around 2/1 000 adults aged <40 years, and around 1-4/1 000 adults aged 40-50 years. They then increased rapidly after age 50 years to around 7-8/1 000, up to 10/1 000 after 80 years of age. Our review confirms that in Europe HZ incidence increases with age, and quite drastically after 50 years of age. In all of the 21 studies included in the present review, incidence rates were higher among women than men, and this difference increased with age. This review also highlights the need to identify standardized surveillance methods to improve the comparability of data within European Union Member States and to monitor the impact of VZV immunization on the epidemiology of HZ. CONCLUSIONS: Available data in Europe have shortcomings which make an accurate assessment of HZ incidence and change over time impossible. However, data are indicative that HZ incidence is comparable, and increases with age in the same proportion across Europe.

Cost-effectiveness of influenza vaccination with a high dose quadrivalent vaccine of the elderly population in Belgium, Finland, and Portugal.

BACKGROUND: Seasonal influenza may result in severe outcomes, resulting in a significant increase of hospitalizations during the winter. To improve the protection provided by the standard dose influenza quadrivalent vaccine (SDQIV), a high-dose vaccine (HDQIV) has been developed specifically for adults aged 60 and older who are at higher risk of life-threatening complications. OBJECTIVES: The aim of this study was to determine the cost-effectiveness of HD QIV vs. SD-QIV in the recommended population of three European countries: Belgium, Finland and Portugal. METHODS: A cost-utility analysis comparing HDQIV vs. SDQIV was conducted using a decision tree estimating health outcomes conditional on influenza: cases, general practitioner and emergency department visits, hospitalizations and deaths. To account for the full benefit of the vaccine, an additional outcome-hospitalizations attributable to influenza-was also evaluated. Demographic, epidemiological and economic inputs were based on the respective local data. HDQIV relative vaccine efficacy vs. SDQIV was obtained from a phase IV efficacy randomized clinical trial. The incremental cost-effectiveness ratios (ICER) were computed for each country, and a probabilistic sensitivity analysis (1,000 simulations per country) was performed to assess the robustness of the results. RESULTS: In the base case analysis, HDQIV resulted in improved health outcomes (visits, hospitalizations, and deaths) compared to SDQIV. The ICERs computed were 1,397, 9,581, and 15,267 €/QALY, whereas the PSA yielded 100, 100, and 84% of simulations being cost-effective at their respective willingness-to-pay thresholds, for Belgium, Finland, and Portugal, respectively. CONCLUSION: In three European countries with different healthcare systems, HD-QIV would contribute to a significant improvement in the prevention of influenza health outcomes while being cost-effective.

Investigating confounding in network-based test-negative design influenza vaccine effectiveness studies-Experience from the DRIVE project.

BACKGROUND: Establishing a large study network to conduct influenza vaccine effectiveness (IVE) studies while collecting appropriate variables to account for potential bias is important; the most relevant variables should be prioritized. We explored the impact of potential confounders on IVE in the DRIVE multi-country network of sites conducting test-negative design (TND) studies. METHODS: We constructed a directed acyclic graph (DAG) to map the relationship between influenza vaccination, medically attended influenza infection, confounders, and other variables. Additionally, we used the Development of Robust and Innovative Vaccines Effectiveness (DRIVE) data from the 2018/2019 and 2019/2020 seasons to explore the effect of covariate adjustment on IVE estimates. The reference model was adjusted for age, sex, calendar time, and season. The covariates studied were presence of at least one, two, or three chronic diseases; presence of six specific chronic diseases; and prior healthcare use. Analyses were conducted by site and subsequently pooled. RESULTS: The following variables were included in the DAG: age, sex, time within influenza season and year, health status and comorbidities, study site, health-care-seeking behavior, contact patterns and social precautionary behavior, socioeconomic status, and pre-existing immunity. Across all age groups and settings, only adjustment for lung disease in older adults in the primary care setting resulted in a relative change of the IVE point estimate >10%. CONCLUSION: Our study supports a parsimonious approach to confounder adjustment in TND studies, limited to adjusting for age, sex, and calendar time. Practical implications are that necessitating fewer variables lowers the threshold for enrollment of sites in IVE studies and simplifies the pooling of data from different IVE studies or study networks.

The feasibility of pragmatic influenza vaccine randomized controlled real-world trials in Denmark and England.

We estimated the frequency of non-specific influenza-associated clinical endpoints to inform the feasibility of pragmatic randomized controlled trials (RCT) assessing relative vaccine effectiveness (rVE). Hospitalization rates of respiratory, cardiovascular and diabetic events were estimated from Denmark and England's electronic databases and stratified by age, comorbidity and influenza vaccination status. We included a seasonal average of 4.5 million Danish and 7.2 million English individuals, 17 and 32% with comorbidities. Annually, approximately 1% of Danish and 0.5% of English individuals were hospitalized for selected events, ~50% of them respiratory. Hospitalization rates were 40-50-fold and 2-10-fold higher in those >50 years and with comorbidities, respectively. Our findings suggest that a pragmatic RCT using non-specific endpoints is feasible. However, for outcomes with rates <2.5%, it would require randomization of ~100,000 participants to have the power to detect a rVE difference of ~13%. Targeting selected groups (older adults, those with comorbidities) where frequency of events is high would improve trial efficiency.

A comparison of coronavirus disease 2019 and seasonal influenza surveillance in five European countries: France, Germany, Italy, Spain and the United Kingdom.

BACKGROUND: In response to the coronavirus disease (COVID-19) outbreak that unfolded across Europe in 2020, the World Health Organisation (WHO) called for repurposing existing influenza surveillance systems to monitor COVID-19. This analysis aimed to compare descriptively the extent to which influenza surveillance systems were adapted and enhanced and how COVID-19 surveillance could ultimately benefit or disrupt routine influenza surveillance. METHODS: We used a previously developed framework in France, Germany, Italy, Spain and the United Kingdom to describe COVID-19 surveillance and its impact on influenza surveillance. The framework divides surveillance systems into seven subsystems and 20 comparable outcomes of interest and uses five evaluation criteria based on WHO guidance. Information on influenza and COVID-19 surveillance systems were collected from publicly available resources shared by European and national public health agencies. RESULTS: Overall, non-medically attended, virological, primary care and mortality surveillance were adapted in most countries to monitor COVID-19, although community, outbreak and hospital surveillance were reinforced in all countries. Data granularity improved, with more detailed demographic and medical information recorded. A shift to systematic notification for cases and deaths enhanced both geographic and population representativeness, although the sampling strategy benefited from the roll out of widespread molecular testing. Data communication was greatly enhanced, contributing to improved public awareness. CONCLUSIONS: Well-established influenza surveillance systems are a key component of pandemic preparedness, and their upgrade allowed European countries to respond to the COVID-19 pandemic. However, uncertainties remain on how both influenza and COVID-19 surveillance can be jointly and durably implemented.

Cost-utility analysis of influenza vaccination in a population aged 65 years or older in Spain with a high-dose vaccine versus an adjuvanted vaccine.

BACKGROUND: The normal ageing process is accompanied by immunosenescence and a progressive weakening of the immune system. High-dose inactivated influenza quadrivalent vaccine (HD-QIV) has shown greater immunogenicity, relative efficacy, and effectiveness than the standard-dose inactivated quadrivalent vaccine (SD-QIV). The aim of the study was to assess the cost-utility of an HD-QIV strategy compared with an adjuvanted trivalent inactivated vaccine (aTIV) strategy in the population above 65 years of age in Spain. METHODS: We evaluated the public health and economic benefits of alternatives by using a decision-tree model, which included influenza cases, visits to the general practitioner (GP), visits to the emergency department (ED), hospitalisations, and mortality related to influenza. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economical sources of uncertainty. RESULTS: Our results show that switching from aTIV strategy to HD-QIV would prevent 36,476 cases of influenza, 5,143 visits to GP, 1,054 visits to the ED, 9,193 episodes of hospitalisation due to influenza or pneumonia, and 357 deaths due to influenza - increasing 3,514 life-years and 3,167 quality-adjusted life-years (QALYs). Healthcare costs increase by €78,874,301, leading to an incremental cost-effectiveness ratio (ICER) of €24,353/QALY. The sensitivity analysis indicates that the results are rather robust. CONCLUSION: Our analysis shows that HD-QIV in people over 65 years of age is an influenza-prevention strategy that is at least cost-effective, if not dominant, in Spain. It reduces cases of influenza, GP visits, hospitalisations, deaths, and associated healthcare costs.

Patient and practice level factors associated with seasonal influenza vaccine uptake among at-risk adults in England, 2011 to 2016: An age-stratified retrospective cohort study.

We sought to gain insights into the determinants of seasonal influenza vaccine (SIV) uptake by conducting an age-stratified analysis (18-64 and 65+) of factors associated with SIV uptake among at-risk adults registered to English practices. Records for at-risk English adults between 2011 and 2016 were identified using the Clinical Practice Research Datalink database. SIV uptake was assessed annually. The associations of patient, practice, and seasonal characteristics with SIV uptake were assessed via cross-sectional and longitudinal analyses, using mixed-effects and general estimating equation logistic regression models. Overall SIV uptake was 35.3% and 74.0% for adults 18-64 and 65+, respectively. Relative to white patients, black patients were least likely to be vaccinated (OR18-64: 0.82 (95% CI: 0.80, 0.85); OR65+: 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR18-64: 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR18-64: 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR65+: 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR18-64: 2.33 (95% CI: 2.31, 2.36); OR65+: 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR18-64: 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR65+: 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR18-64: 0.68 (95% CI: 0.67, 0.70); OR65+: 0.97 (95% CI: 0.94, 0.99)). Prior influenza season severity and vaccine effectiveness were marginally predictive of uptake. Our age-stratified analysis uncovered SIV uptake disparities by ethnicity, sex, age, socioeconomic deprivation, and co-morbidities, warranting further attention by GPs and policymakers alike.

From trivalent to quadrivalent influenza vaccines: Public health and economic burden for different immunization strategies in Spain.

PURPOSE: Quadrivalent influenza vaccine (QIV) includes the same strains as trivalent influenza vaccine (TIV) plus an additional B strain of the other B lineage. The aim of the study was to analyse the public health and economic impact of replacing TIV with QIV in different scenarios in Spain. METHODS: A dynamic transmission model was developed to estimate the number of influenza B cases prevented under TIV and QIV strategies (<65 years (high risk) and ≥65 years). This model considers cross-protective immunity induced by different lineages of influenza B. The output of the transmission model was used as input for a decision tree model that estimated the economic impact of switching TIV to QIV. The models were populated with Spanish data whenever possible. Deterministic univariate and probabilistic multivariate sensitivity analyses were performed. RESULTS: Replacing TIV with QIV in all eligible patients with current vaccine coverage in Spain may have prevented 138,707 influenza B cases per season and, therefore avoided 10,748 outpatient visits, 3,179 hospitalizations and 192 deaths. The replacement could save €532,768 in outpatient visit costs, €13 million in hospitalization costs, and €3 million in costs of influenza-related deaths per year. An additional €5 million costs associated with productivity loss could be saved per year, from the societal perspective. The budget impact from societal perspective would be €6.5 million, and the incremental cost-effectiveness ratio (ICER) €1,527 per quality-adjusted life year (QALY). Sensitivity analyses showed robust results. In additional scenarios, QIV also showed an impact at public health level reducing influenza B related cases, outpatient visits, hospitalizations and deaths. CONCLUSIONS: Our results show public health and economic benefits for influenza prevention with QIV. It would be an efficient intervention for the Spanish National Health Service with major health benefits especially in the population ≥65-year.

Determinants of shingles vaccine acceptance in the United Kingdom.

BACKGROUND: The United Kingdom (UK) was the first European country to introduce a national immunisation program for shingles (2013-2014). That year, vaccination coverage ranged from 50 to 64% across the UK, but uptake has declined ever since. This study explored determinants of the acceptance of the shingles vaccine in the UK. METHODS: Vaccinated and unvaccinated individuals, who were eligible for the last catch-up cohort of the 2014-2015 shingles vaccination campaign, were identified using the Clinical Practice Research Datalink (the National Health Service data research service) and invited to participate by their general practitioner (GP). An anonymised self-administered questionnaire was developed using the Health Belief Model as a theoretical framework, to collect data on demographic and socio-economic characteristics, health status, knowledge, influences, experiences and attitudes to shingles and the shingles vaccine. Multivariable logistic regression was used to identify the factors associated with vaccination. Physicians' views concerning perceived barriers to vaccination were also assessed. RESULTS: Of the 2,530 questionnaires distributed, 536 were returned (21.2%) from 69 general practices throughout the UK. The majority of responders were female (58%), lived in care homes (56%) and had completed secondary or higher education (88%). There were no differences between vaccinated and unvaccinated responders. Being offered the shingles vaccine by a GP/nurse (odds ratio (OR) = 2.3), and self-efficacy (OR = 1.2) were associated with being vaccinated (p<0.05). In contrast, previous shingles history (OR = 0.4), perceived barriers to vaccination (OR = 0.7) and perceived control of the disease (OR = 0.7) were associated with not being vaccinated against shingles (p<0.05). Less than half (44.0%) of GPs were aware of the local communication campaigns regarding shingles and the shingles vaccine. CONCLUSIONS: Socio-psychological factors largely influence shingles vaccination acceptance in this study. The results add to existing evidence that healthcare providers (HCPs) have a pivotal role against vaccine hesitancy. Campaigns focusing on GPs and accessible information offered to eligible members of the public can further enhance shingles vaccine uptake.