Vittorio Demicheli

Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review.

BACKGROUND Influenza vaccination of elderly individuals is recommended worldwide. Our aim was to review the evidence of efficacy and effectiveness of influenza vaccines in individuals aged 65 years or older. METHODS We searched five electronic databases to December, 2004, in any language, for randomised (n=5), cohort (n=49), and case-control (n=10) studies, assessing efficacy against influenza (reduction in laboratory-confirmed cases) or effectiveness against influenza-like illness (reduction in symptomatic cases). We expressed vaccine efficacy or effectiveness as a proportion, using the formula VE=1-relative risk (RR) or VE*=1-odds ratio (OR). We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications, and deaths. FINDINGS In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6-36) and non-significant against influenza (RR 1.04, 0.43-2.51). Well matched vaccines prevented pneumonia (VE 46%, 30-58) and hospital admission (VE 45%, 16-64) for and deaths from influenza or pneumonia (VE 42%, 17-59), and reduced all-cause mortality (VE 60%, 23-79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02-2.01), influenza-like illness (RR 1.05, 0.58-1.89), or pneumonia (RR 0.88, 0.64-1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12-38) and all-cause mortality (VE 42%, 24-55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21-33), respiratory diseases (VE* 22%, 15-28), and cardiac disease (VE* 24%, 18-30), and for all-cause mortality (VE* 47%, 39-54). INTERPRETATION In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest.

Antivirals for influenza in healthy adults: systematic review.

BACKGROUND Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. METHODS We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. FINDINGS We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations (2.54, 1.50-4.31), and withdrawals because of adverse events (2.54, 1.60-4.06). There was no effect on asymptomatic cases (RR 0.85, 0.40-1.80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0.99 days, -1.26 to -0.71), but had no effect on nasal shedding of influenza A viruses (0.93, 0.71-1.21). The fewer data for rimantadine showed comparable effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1.79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza. INTERPRETATION The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.

Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review

BACKGROUND We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age. METHODS We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts, and Science Citation Index to June, 2004, in any language, and contacted vaccine manufacturers and authors of relevant studies to identify additional data. We included randomised, cohort, and case-control studies comparing efficacy of vaccines against influenza (reduction in laboratory-confirmed cases), effectiveness of vaccines against influenza-like illness (reduction in symptomatic cases), or both, with placebo or no intervention. We analysed the following outcomes: influenza, influenza-like illness, admissions, school absences, complications, and secondary transmission. FINDINGS We included 14 randomised controlled trials, eight cohort studies, one case-control study, and one randomised controlled trial of intraepidemic use of the vaccines. Live attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children older than 2 years compared with placebo or no immunisation. Inactivated vaccines had lower efficacy (65%) than live attenuated vaccines, and in children aged 2 years or younger they had similar effects to placebo. Effectiveness of inactivated vaccines was about 28% in children older than 2 years. Vaccines were effective in reducing long school absences (relative risk 0.14 [95% CI 0.07-0.27]). Studies assessing the effects of vaccines against secondary cases, lower-respiratory tract disease, acute otitis media, and hospital stay suggested no difference with placebo or standard care, but lacked statistical power. INTERPRETATION Influenza vaccines (especially two-dose live attenuated vaccines) are efficacious in children older than 2 years. Efficacy and effectiveness of the vaccines differed strikingly. Only two small studies assessed the effects of influenza vaccines on hospital admissions and no studies assessed reductions in mortality, serious complications, and community transmission of influenza. If influenza immunisation in children is to be recommended as public-health policy, large-scale studies assessing such important outcomes and undertaking direct comparisons of vaccines are urgently needed.

Influenza vaccination for health-care workers who work with elderly people in institutions : a systematic review

Our aim was to review the evidence of efficacy and effectiveness of influenza vaccination of health-care workers in reducing cases of influenza-like illness, influenza, complications from influenza, death from influenza, and death from all causes among the elderly people they care for in institutions. We searched 11 electronic databases in any language and identified two cluster-randomised controlled trials with moderate risk of bias and one cohort study at high risk of bias that addressed our questions. Staff vaccination had a significant effect on influenza-like illness (vaccine effectiveness [VE] 86%, 95% CI 40-97%) only when patients were vaccinated too. If patients were not vaccinated, staff immunisation had no effect. Vaccinating health-care workers did not appear efficacious against influenza (RR 0.87, 95% CI 0.46-1.63). There was no significant effect of vaccination on lower respiratory tract infections: (RR 0.70, 95% CI 0.41-1.20). Deaths from pneumonia were significantly reduced (VE 39%, 95% CI 2-62%), as were deaths from all causes (VE 40%, 95% CI 27-50%). These findings must be interpreted in the light of possible selection, performance, attrition, and detection biases.

Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review

Objective To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines. Design Systematic review without meta-analysis. Data extraction Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out. Data synthesis We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were less likely to have conclusions favouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences between means 5.04). Study size was not associated with concordance, content of take home message, funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding. Conclusion Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size.

The effectiveness and safety of vaccines against human anthrax: a systematic review

We report on the results of a systematic review of existing controlled clinical trials undertaken to assess the effectiveness and safety of vaccines against human anthrax in relation to disease incidence and side-effects. Two articles retrieved by electronic and hand search fulfilling some of the inclusion criteria underwent a quality assessment by a group of reviewers. Data synthesized from the two trials showed that estimates of overall effectiveness and safety favour treatment (overall odds ratio 0.16; 95% confidence interval 0.07-0.34). The route of inoculation appears to make little difference to the effectiveness of the vaccines; however, one study shows that the incidence and severity of side-effects are significantly higher with the killed vaccine than with the alum-based placebo (overall odds ratio 0.16; 95% confidence interval 2.38-27.17).

Quality of economic evaluations in health care : It is time for action to ensure higher methodological quality

Economic evaluation is becoming established globally as one of the tools for decision making in health care.1 Its rise in popularity is reflected by the increasing number of published economic evaluations. One source estimates that 1803 economic evaluations were published in medical journals in 1979-90,2 rising to 2222 in 1991-6.3 This increase in both the availability of economic evaluations and willingness to use their results to allocate scarce resources reinforces the need for evaluations to be methodologically sound so that the consequent healthcare decisions are ethically defensible. Do our current economic evaluations meet the necessary methodological requirements? In the early 1990s several systematic reviews cast doubt on the scientific reliability of some published evaluations. All advocated better standards of conducting and reporting economic evaluations.4–7 A subsequent survey among editors of medical journals found that none had a coherent editorial policy for economic evaluations, and few had peer reviewers with knowledge …

The effectiveness and safety of hepatitis A vaccine: a systematic review.

We report on the conduct of a systematic review to assess the efficacy and the safety of hepatitis A vaccines in adults and children. We identified, retrieved, and assessed all trials evaluating the effects of hepatitis A vaccines on prevention of cases of hepatitis A, death from hepatitis A, and assessing nature and frequency of adverse events. We included eight randomised trials, four containing efficacy outcomes, three containing only safety outcomes and a single study containing efficacy and adverse events outcomes. Combined inactivated vaccine effectiveness was 86% (95% CI: 63-95%). Combined attenuated vaccine effectiveness was 95% (95% CI: 81-99%). Inactivated vaccine effectiveness in the prevention of HAV secondary cases, compared to non-intervention was 82% (95% CI: 23-96%). Safety profile of vaccines was similar to that of their comparators. Despite poor design and reporting of trials, we found convincing evidence of the effectiveness and safety of inactivated HAV vaccines.

Hepatitis B vaccination and multiple sclerosis: evidence from a systematic review

An association between administration of hepatitis B vaccine (HBV) and onset or relapse of multiple sclerosis (MS) and other demyelinating diseases (DD) surfaced in the mid-1990s and led to an increase of studies investigating the association. Evidence from these studies, gathered within a systematic review of evidence of safety of HBV is presented. Nine published and two unpublished comparative studies identified in the Cochrane Library, MEDLINE, Embase, Current

A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy

Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during pregnancy but, because of the reduced statistical power, meta-analyses and large multi-centres studies are needed in order to obtain more conclusive results, especially for rare outcomes.