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.

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.

Spirulina as a daily nutritional supplement of young pre-school Cambodian children of deprived settings: a single-blinded, placebo-controlled, cross-over trial.

BACKGROUND: Spirulina (SP) is widely used as a nutritional supplement to enhance child nutrition in low-income countries. We assessed Spirulina's efficacy of the current dose supplied by institutions in Cambodia on improving growth and anemia in a cross-over randomized controlled trial in preschool underprivileged children from similar settings. METHODS: Preschool children cared by a not-for-profit institution were randomly and blindly allocated (2 to 1) to spirulina or placebo: 100 g in total, given in 2 g per day. After 5 weeks of wash-out, participants were crossed-over to the other group. Anthropometric gain and selected hematological data (blood cell count, ferritin, and C-reactive protein) were assessed at each phase. RESULTS: A total of 179 children completed the trial, 149 (83.2%) completed all the anthropometrics, and 99 (55.3%) all hematological measures. Mean BMI was 14.18 (95%CI: 14.00-14.37) and 31(20.8%) children had thinness. Mean blood hemoglobin was 11.9 g/dL (95%CI: 11.8-12.1). The weight gain of the SP group showed a modest higher trend compared to placebo (0.63 kg; 95%CI: 0.54-0.72 and 0.46 kg; 95%CI: 0.33-0.58, respectively; p = 0.07). Height increased similarly in both groups. The number of anemic children decreased by 6 (6.06%) and 11 (11.11%) on Placebo or SP, respectively (p = 0.004). Tolerance was good. CONCLUSION: SP may be recommended to improve childhood anemia. The analysis of the usual daily dose (2 g) provided by organizations in Cambodia shows a tendency to improve weight gain in the group supplemented with SP very close to significance, but no trend in height. Increased doses and longer supplementation should be evaluated further. TRIAL REGISTRATION: The study was retrospectively registered at ISRCTN under number 11696165 on 12/12/2018.

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.

Looking Back on 50 Years of Literature to Understand the Potential Impact of Influenza on Extrapulmonary Medical Outcomes.

We conducted a scoping review of the epidemiological literature from the past 50 years to document the contribution of influenza virus infection to extrapulmonary clinical outcomes. We identified 99 publications reporting 243 associations using many study designs, exposure and outcome definitions, and methods. Laboratory confirmation of influenza was used in only 28 (12%) estimates, mostly in case-control and self-controlled case series study designs. We identified 50 individual clinical conditions associated with influenza. The most numerous estimates were of cardiocirculatory diseases, neurological/neuromuscular diseases, and fetal/newborn disorders, with myocardial infarction the most common individual outcome. Due to heterogeneity, we could not generate summary estimates of effect size, but of 130 relative effect estimates, 105 (81%) indicated an elevated risk of extrapulmonary outcome with influenza exposure. The literature is indicative of systemic complications of influenza virus infection, the requirement for more effective influenza control, and a need for robust confirmatory studies.

The economic burden of influenza among adults aged 18 to 64: A systematic literature review.

While the economic burden of influenza infection is well described among adults aged 65 and older, less is known about younger adults. A systematic literature review was conducted to describe the economic burden of seasonal influenza in adults aged 18 to 64 years, to identify the main determinants of direct and indirect costs, and to highlight any gaps in the existing published evidence. MEDLINE and Embase were searched from 2007 to February 7, 2020, for studies reporting primary influenza-related cost data (direct or indirect) or absenteeism data. Of the 2613 publications screened, 51 studies were included in this review. Half of them were conducted in the United States, and 71% of them described patients with influenza-like illness rather than laboratory-confirmed disease. Only 12 studies reported cost data specifically for at-risk populations. Extracted data highlighted that within the 18- to 64-year-old group, up to 88% of the economic burden of influenza was attributable to indirect costs, and up to 75% of overall direct costs were attributable to hospitalizations. Furthermore, within the 18- to 64-year-old group, influenza-related costs increased with age and underlying medical conditions. The reported cost of influenza-related hospitalizations was found to be up to 2.5 times higher among at-risk populations compared with not-at-risk populations. This review documents the considerable economic impact of influenza among adults aged 18 to 64. In this age group, most of the influenza costs are indirect, which are generally not recognized by decision makers. Future studies should focus on at-risk subgroups, lab-confirmed cases, and European countries.