Background: Injected cholera vaccines are rarely used today, although they may have some benefit. It is valuable to summarize the evidence for effectiveness of injected cholera vaccines for comparison with newer oral vaccines (subject of a separate Cochrane Review). Objectives: To evaluate killed whole cell (KWC) cholera vaccines and other inactive subunit vaccines (administered by injection) for preventing cholera and death, and to evaluate the adverse effects. Search methods: In September 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), EMBASE, and LILACS. We also searched reference lists and handsearched the journal Vaccine up to 1997. Selection criteria: Randomized and quasi-randomized controlled trials comparing injected cholera vaccines (KWC or other inactive subunit) with placebo, control vaccines, or no intervention in adults and children irrespective of immune status or special risk category. Data collection and analysis: Two authors extracted data and assessed trial methodological quality independently. Dichotomous data were reported using the risk ratio (RR) with 95% confidence intervals (CI). Vaccine efficacies were also calculated (% vaccine efficacy = (1-RR) x 100%). Main results: Sixteen trials, involving over one million adults, children and infants, fulfilled the inclusion criteria. Twenty-four comparisons reported on vaccine efficacy (cholera cases and/or deaths) and 11 comparisons considered adverse effects (nine reported on both). Compared to placebo, vaccinees had a reduced risk of death from cholera (RR 0.49, 95% CI 0.25 to 0.93; 837,442 participants) and a reduced risk of contracting cholera at 12 months (RR 0.52, 95% CI 0.42 to 0.65, random-effects model; 1,512,573 participants). This translates to an efficacy of 48%, 95% confidence interval 35% to 58%. Significant protection lasted for two years, even after only a single dose, and for three years with an annual booster. Children over five years and adults were protected for up to three years, while children under five years were protected for up to a year. Injected cholera vaccines were associated with more systemic and local adverse effects compared to placebo, but these were not severe or life-threatening. Authors' conclusions: Injected cholera vaccines appear to be safe and relatively more effective than usually realized. Protection against cholera persists for up to two years following a single dose of vaccine, and for three years with an annual booster. However, they have been superseded by oral vaccines. 23 April 2019. No update planned. Other. This is not a current question.
\n \n\n \n \nHepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted. \u00a9 2002 Wiley-Liss, Inc.
\n \n\n \n \nAdaptations to the recognized methods of systematic reviewing are required when addressing questions about safety, particularly about rare and/or long-term serious adverse events. Conducting a systematic review of vaccine safety requires the implementation of novel strategies for locating studies, the use of experimental instruments to assess the quality of non-randomized studies, and the employment of pooling methods for non-randomized data, where appropriate. Standardizing both the indexing of adverse event data on electronic libraries and their reporting would improve the potential of systematic reviews of vaccine to draw accurate conclusions about the safety of a vaccine. \u00a9 2004 Elsevier Ltd. All rights reserved.
\n \n\n \n \nBackground: Healthcare workers' (HCWs) influenza rates are unknown, but may be similar to the general public and they may transmit influenza to patients. Objectives: To identify studies of vaccinating HCWs and the incidence of influenza, its complications and influenza-like illness (ILI) in individuals \u2265 60 in longterm care facilities (LTCFs). Search strategy: We searched CENTRAL (The Cochrane Library 2009, issue 3), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2009), EMBASE (1974 to 2009) and Biological Abstracts and Science Citation Index-Expanded. Selection criteria: Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of HCWs caring for individuals \u2265 60 in LTCFs and the incidence of laboratory-proven influenza, its complications or ILI. Data collection and analysis: Two authors independently extracted data and assessed risk of bias. Main results: We identified four cluster-RCTs (C-RCTs) (n = 7558) and one cohort (n = 12742) of influenza vaccination for HCWs caring for individuals \u2265 60 in LTCFs. Pooled data from three C-RCTs showed no effect on specific outcomes: laboratoryproven influenza, pneumonia or deaths from pneumonia. For non-specific outcomes pooled data from three C-RCTs showed HCW vaccination reduced ILI; data from one C-RCT that HCW vaccination reduced GP consultations for ILI; and pooled data from three C-RCTs showed reduced all-cause mortality in individuals \u2265 60. Authors' conclusions: No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals \u2265 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals \u2265 60. The key interest is preventing laboratory-proven influenza in individuals \u2265 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratoryproven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination. \u00a9 2010 The Cochrane Collaboration.
\n \n\n \n \nBackground: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a world-wide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. Objectives: To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2); MEDLINE (1966 to May 2009); OLDMEDLINE (1950 to 1965); EMBASE (1990 to May 2009); and CINAHL (1982 to May 2009). Selection criteria: We scanned 2958 titles, excluded 2790 and retrieved the full papers of 168 trials, to include 59 papers of 60 studies. We included any physical interventions (isolation, quarantine, social distancing, barriers, personal protection and hygiene) to prevent transmission of respiratory viruses. We included the following study designs: randomised controlled trials (RCTs), cohorts, case controls, cross-over, before-after, and time series studies. Data collection and analysis: We used a standardised form to assess trial eligibility. RCTs were assessed by: randomisation method; allocation generation; concealment; blinding; and follow up. Non-RCTs were assessed for the presence of potential confounders, and classified into low, medium, and high risks of bias. Main results: The risk of bias for the four RCTs, and most cluster RCTs, was high. The observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially 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. 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 N95 respirators were superior to simple surgical masks, but were more expensive, uncomfortable, and caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. There was limited evidence that social distancing was effective especially if related to the risk of Physical interventions to interrupt or reduce the spread of respiratory viruses exposure. Authors' conclusions: 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. \u00a9 Queen's Printer and Controller of HMSO.
\n \n\n \n \nBackground: Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. Objectives: To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Search methods: We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). Selection criteria: In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials\u00a0(RCTs), cohorts, case-controls, before-after and time series studies. Data collection and analysis: We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. Main results: We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. Authors' conclusions: Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.
\n \n\n \n \nObjectives: The purpose of the European network for Health Technology Assessment (EUnetHTA) is to make HTA agencies collaborate sharing methods and tools thus avoiding duplication of evaluative efforts and allowing resource savings. From 2010 to 2012, the activities of the network were carried out through EUnetHTA Joint Action 1 and Work Package 4 Strand B aimed at producing two Core HTAs with two main objectives: to test the Web based Core model and the collaborative working models. Our objective in this article is to give an historical record of the Work Package activities highlighting what worked and what did not in the collaboration of researchers' groups coming from different agencies. Methods: A retrospective description of all the steps for the joint production of the two Core HTAs is provided starting from the first step of selecting technologies of common interest. Primary researchers' views on the whole process have been collected through a semi-structured telephonic interview supported by a questionnaire. Coordinators views were gathered during internal meetings and validated. Results: Majority of respondents thought topic selection procedure was not clear and well managed. About collaborative models, small groups were seen to enable more exchange, whatever the model. According to coordinators, loss of expertise and experience during the production process, different languages, and novelty of the Online Tool were main barriers. Conclusions: Lessons learned from this first experience in Joint Action 1 paved the path for the collaboration in Joint Action 2, as it allowed enhancements and changes in models of collaborations and coordination.
\n \n\n \n \nBackground: A framework for collaborative production and sharing of HTA information, the HTA Core Model, was originally developed within EUnetHTA in 2006-08. In this paper, we describe the further development of the Model to allow implementation and utilization of the Model online. The aim was to capture a generic HTA process that would allow effective use of the HTA Core Model and resulting HTA information while at the same time not interfering with HTA agencies' internal processes. Methods: The work was coordinated by a development team in Finland, supported by an international expert group. Two pilot testing rounds were organized among EUnetHTA agencies and two extensive core HTA projects tested the tool in a real setting. The final work was also formally validated by a group of HTA agencies. Results: The HTA Core Model Online - available at http://www.corehta.info - is a web site hosting a) a tool to allow electronic utilization of the HTA Core Model and b) a database of produced HTA information. While access to the HTA information is free to all, the production features are currently available to EUnetHTA member agencies only. A policy was crafted to steer the use of the Model and produced information. Conclusions: We have successfully enabled electronic use of the HTA Core Model and agreed on a policy for its utilization. The system is already being used in subsequent HTA projects within EUnetHTA Joint Action 2. Identified shortcomings and further needs will be addressed in subsequent development.
\n \n\n \n \nIntroduction: We present three systematic reviews carried out within the Cochrane Collaboration, focusing on a different influenza intervention in healthy adults: Vaccines; Ion Channel Inhibitor antivirals and Neuraminidase Inhibitor (NIs) antivirals. The objectives were to identify, retrieve and assess all studies evaluating the effects of these interventions in prophylaxis and early treatments of influenza and the frequency of adverse events. Additionally we present the results of the economic evaluation of effective alternatives in order to define the most cost-effective intervention. The economic evaluation is set in the context of the British Army. Methods: Studies were identified using a standard Cochrane search strategy. Any randomised or quasi-randomised studies in healthy individuals aged 14-60 years were considered for inclusion in the systematic review. Those which met inclusion criteria were assessed for quality and their data meta-analysed. The economic model was constructed using Cost-effectiveness and Cost-utility study designs. Results: Live aerosol vaccines reduced cases of clinical influenza A with virological confirmation (by serology and/or viral isolation) by 48% (95%CI: 24-64%), whilst recommended inactivated parenteral vaccines have an efficacy of 68% (95%CI: 49-79%). Vaccine effectiveness in reducing clinical influenza cases (i.e. without virological confirmation) was lower, with efficacies of 13 and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days (95%CI: 0.1-0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. When compared to placebo for the prevention of influenza, oral amantadine was 61% (95%CI: 51-69%) efficacious (RR 0.39 - 95%CI: 0.31-0.49), and oral rimantadine was 64% (95%CI: 41-78%) efficacious (RR 0.36 - 95%CI: 0.22-0.59). When compared to placebo for the treatment of influenza, oral amantadine significantly shortened duration of fever (by 1.00 days - 95%CI: 0.73-1.29), and oral rimantadine significantly shortened duration of fever (by 1.27 days - 95%CI: 0.77-1.77). When compared to placebo, NIs were 74% (95%CIs: 50-87%) effective in preventing naturally occurring cases of clinically defined influenza. In a treatment role, NIs shortened the duration of symptoms by one day (Weighted Mean Difference - 1.0; 95%CIs: -1.3 to - 0.6) when a clinical case definition is used. The economic results show that in healthy adults, inactivated vaccines appear the best buy. Conclusions: If assessed from the point of view of effectiveness and efficiency, vaccines are undoubtedly the best preventive means for clinical influenza in healthy adults. However, when safety and quality of life considerations are included, parenteral vaccines have such low effectiveness and high incidence of trivial local adverse effects that the trade-off is unfavourable. This is so even when the incidence of influenza is high and adverse effect quality of life preferences are rated low. We reached similar conclusions for antivirals and NIs even at high influenza incidence levels. On current evidence we conclude in healthy adults aged 14-60 the most cost-effective option is not to take any action.
\n \n\n \n \nContext: The quality of a process can only be tested against its agreed objectives. Editorial peer-review is widely used, yet there appears to be little agreement about how to measure its effects or processes. Methods: To identify outcome measures used to assess editorial peer review as performed by biomedical journals, we analyzed studies identified from 2 systematic reviews that measured the effects of editorial peer review on the quality of the output (ie, published articles) or of the process itself (eg, reviewers' comments). Results: Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review. Only 1, nonrandomized study compared the quality of articles published in peer-reviewed and non-peer-reviewed journals. The others measured the effects of variations in the peer-review process or used a before-and-after design to measure the effects of standard peer review on accepted articles. Eighteen studies measured the quality of reviewers' reports under different conditions such as blinding or after training. One study compared the time and cost of different review processes. Conclusions: Until we have properly defined the objectives of peer-review, it will remain almost impossible to assess or improve its effectiveness. The research needed to understand the broader effects of peer review poses many methodologic problems and would require the cooperation of many parts of the scientific community.
\n \n\n \n \nContext: Reviews performed almost a decade ago showed considerable gaps in the quality of reporting and methods applied to economic evaluations of health care interventions. Measures taken by the research community to address the issue included the promulgation of guidelines and the publicizing of good practice in economic evaluation. Methods: To assess the quality of methods of systematic reviews, economic evaluations in health care, and reporting methods, we conducted full-text searches of private and public databases for the period 1990 through March 2001 and corresponded with researchers active in the field. A total of 102 reports were identified, but only 39 were included. Quality of systematic reviews was assessed by a 6-item checklist. Results: Quality of review methods was reasonable, but more attention needs to be paid to search methods and standardization of evaluation instruments. The reviews found consistent evidence of serious methodological flaws in a significant number of economic evaluations. Lack of clear descriptions of methods, lack of explanation and justification for the framework and approach used, and low-quality estimates of effectiveness for the interventions evaluated were the most frequent flaws. Modest improvements in quality of conducting and reporting economic evaluations appear to have taken place in the last decade. Conclusions: Proper allocation of resources on the basis of economic evaluations remains uncertain. Editorial teams and regulatory bodies should perform quality assurance based on a single widely accepted and validated standard instrument.
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