Effectiveness and implementation of influenza vaccination : a non-experimental approach

Large-scale prevention by influenza vaccination aims at reducing post-influenza complications among those who need it at most. This thesis aims at describing the risk of complications and benefits of vaccination. In chapter 2 we determine prognostic factors for influenza-associated hospitalization or death during the 1996/97 influenza A epidemic in a case-control study among adult patients with high-risk medical conditions. The presence of chronic obstructive pulmonary disease, heart failure, previous hospitalization, high GP visiting rate and poly-pharmacy were prognostic factors for influenza, bronchitis, pneumonia, diabetes, heart failure or myocardial infarction, particularly in patients of working-age. In chapter 3 we describe the development and validation of a clinical prediction rule for the need for hospitalization for influenza or pneumonia, or death using databases covering over 120,000 non-institutionalized US senior citizens. The accuracy of the rule in the derivation cohort was high when a cut-off sum-score ?50 points is chosen (sensitivity:89%, specificity:51%) while only 50% of seniors would have to be selected for vaccination. In chapter 4 we describe several design and analytical methods aimed at limiting or preventing confounding by indication in non-experimental safety and effectiveness studies. In chapter 5 we describe a two-season retrospective cohort study covering the 1995/96 and 1996/97 influenza outbreaks among 349 asthmatics aged 0?12 years. A statistically higher pooled vaccine protectiveness of 55% (95% CI 20?75%) was observed among preschool children with asthma compared with those aged 6?12 years: -5% (-81?39%). In chapter 6 we assessed the cost-effectiveness of influenza vaccination among 1,696 adult patients with chronic lung disease followed up during the 1995/96 influenza A epidemic. The incidence of low respiratory tract infection, acute cardiac disease or all-cause death was 15%. No benefits were observed among patients of working-age. Among elderly vaccinees, the occurrence of any complication was reduced by 50% (95% CI 17?70%). The economical benefit was estimated at £50 per elderly vaccinee. In chapter 7 we present a prospective nested case-control study in 41 (1998/99 influenza B epidemic) and 52 (1999/2000 influenza A epidemic) primary care centers We studied 4241 patients with asthma or COPD of working-age in season one and 5966 in season two. After adjustments, vaccination was not associated with reductions in exacerbations of lung disease, pneumonia, heart failure, or myocardial infarction (pooled odds ratio: 1.07; 95% CI 0.63-?1.80). In chapter 8 we assess the risk for hospitalization or death and the effectiveness of influenza vaccination among subgroups of over 120,000 elderly persons. 55?118 high-risk persons and 264?290 healthy persons needed to be vaccinated to prevent one hospitalization or death. In the last part we assessed the effectiveness of a nationwide multi-faceted prevention program involving general practitioners (GP) on influenza immunization practice using a before-and-after study design. During the period 1995?1997, a variety of behavioral methods was implemented to enhance physician adoption of the immunization guideline. In 988 practices all influenza vaccination characteristics markedly improv-e-d from 1995 to 1997. We conclude that a coordinated approach involving primary care physicians can succeed in enlarging the public health impact of a population-based preventive measure