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.
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.
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).
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.
Different types of influenza vaccines are currently produced world-wide. Healthy adults are at present targeted only in North America. Despite the publication of a large number of clinical trials, ...there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has a negative impact on their acceptance and uptake.
To identify, retrieve and assess all studies evaluating the effects (efficacy, effectiveness and harms) of vaccines against influenza in healthy adults.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2005) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to January 2006); and EMBASE (1990 to January 2006). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review.
Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, no intervention. Live, attenuated, or killed vaccines or fractions of them administered by any route, irrespective of antigenic configuration were assessed. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 16 to 65 years were considered. Comparative non-randomised studies were included if they assessed evidence of the possible association between influenza vaccines and serious harms.
Two review authors independently assessed trial quality and extracted data.
Forty-eight reports were included: 38 (57 sub-studies) were clinical trials providing data about effectiveness, efficacy and harms of influenza vaccines and involved 66,248 people; 8 were comparative non-randomised studies and tested the association of the vaccines with serious harms; 2 were reports of harms which could not be introduced in the data analysis. Inactivated parenteral vaccines were 30% effective (95% CI 17% to 41%) against influenza-like illness, and 80% (95% CI 56% to 91%) efficacious against influenza when the vaccine matched the circulating strain and circulation was high, but decreased to 50% (95% CI 27% to 65%) when it did not. Excluding the studies of the 1968 to 1969 pandemic, effectiveness was 15% (95% CI 9% to 22%) and efficacy was 73% (95% CI 53% to 84%). Vaccination had a modest effect on time off work, but there was insufficient evidence to draw conclusions on hospital admissions or complication rates. Inactivated vaccines caused local tenderness and soreness and erythema. Spray vaccines had more modest performance. Monovalent whole-virion vaccines matching circulating viruses had high efficacy (VE 93%, 95% CI 69% to 98%) and effectiveness (VE 66%, 95% CI 51% to 77%) against the 1968 to 1969 pandemic.
Influenza vaccines are effective in reducing cases of influenza, especially when the content predicts accurately circulating types and circulation is high. However, they are less effective in reducing cases of influenza-like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications. Whole-virion monovalent vaccines may perform best in a pandemic.
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.
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.
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.
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.
Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.Data sources Cochrane Library, Medline, OldMedline, ...Embase, and CINAHL, without restrictions on language or publication.Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias.Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure—that is, the higher the risk the longer the distancing period.Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.
Positron emission tomography is one of the most mature techniques for monitoring the particles range in hadron therapy, aiming to reduce treatment uncertainties and therefore the extent of safety ...margins in the treatment plan. In-beam PET monitoring has been already performed using inter-spill and post-irradiation data, i.e. while the particle beam is off or paused. The full beam acquisition procedure is commonly discarded because the particle spills abruptly increase the random coincidence rates and therefore the image noise. This is because random coincidences cannot be separated by annihilation photons originating from radioactive decays and cannot be corrected with standard random coincidence techniques due to the time correlation of the beam-induced background with the ion beam microstructure. The aim of this paper is to provide a new method to recover in-spill data to improve the images obtained with full-beam PET acquisitions. This is done by estimating the temporal microstructure of the beam and thus selecting input PET events that are less likely to be random ones. The PET detector we used was the one developed within the INSIDE project and tested at the CNAO synchrotron-based facility. The data were taken on a PMMA phantom irradiated with 72 MeV proton pencil beams. The obtained results confirm the possibility of improving the acquired PET data without any external signal coming from the synchrotron or ad hoc detectors.
Viral epidemics or pandemics such as of influenza or severe acute respiratory syndrome (SARS) pose a significant threat. Antiviral drugs and vaccination may not be adequate to prevent catastrophe in ...such an event.
To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses (excluding vaccines and antiviral drugs, which have been previously reviewed).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to November 2006); OLDMEDLINE (1950 to 1965); EMBASE (1990 to November 2006); and CINAHL (1982 to November 2006).
We scanned 2300 titles, excluded 2162 and retrieved the full papers of 138 trials, including 49 papers of 51 studies. The quality of three randomised controlled trials (RCTs) was poor; as were most cluster RCTs. The observational studies were of mixed quality. We were only able to meta-analyse case-control data. We searched for any interventions to prevent viral transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection and hygiene). Study design included RCTs, cohort studies, case-control studies, cross-over studies, before-after, and time series studies.
We scanned the titles, abstracts and full text articles using a standardised form to assess eligibility. RCTs were assessed according to randomisation method, allocation generation, concealment, blinding, and follow up. Non-RCTs were assessed for the presence of potential confounders and classified as low, medium, and high risk of bias.
The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. The six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions about these measures.
Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.
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