1,720,969 research outputs found
Pegylated and non-pegylated interferon-alfa and ribavirin for the treatment of mild chronic hepatitis C: A systematic review and meta-analysis
No full textObjectives: traditionally, patients with chronic hepatitis C virus (HCV) infection have not received treatment until their infection reaches the moderate to severe stage. The aim of this systematic review was to assess the clinical effectiveness of pegylated (PEG) and non-pegylated interferon (IFN) alfa and ribavirin (RBV) for the treatment of adults with histologically mild HCV.Methods: we performed a sensitive search of fourteen electronic bibliographic databases for literature that met criteria defined in a research protocol. Two reviewers independently selected studies, extracted data and assessed methodological quality.Results: ten randomized, controlled trials (RCTs) were included. Treatment with PEG + RBV combination therapy resulted in significantly higher sustained virological response (SVR) rates than treatment with IFN + RBV combination therapy. Treatment for 48 weeks with PEG + RBV was significantly more effective than the same treatment for 24 weeks. Significantly higher SVR rates were seen with IFN + RBV compared with either IFN monotherapy or no treatment. In the meta-analysis (four IFN trials), the relative risk of not experiencing an SVR was 0.59 (95 percent CI, 0.51 – 0.69) and was statistically significant (p < .00001). SVRs were higher for patients with genotype non-1 compared with genotype 1 for both PEG + RBV and IFN + RBV treatments.Conclusions: patients with histologically mild HCV can be successfully treated with both PEG and IFN combination therapy, and response rates are broadly comparable with those achieved in patients with advanced disease. Treating patients in the early milder stages of HCV is, therefore, a clinically effective option<br/
Time to full publication of studies of anti breast cancer, and the potential for publication bias
No full textTime to full publication of studies of anticancer drugs for breast cancer, and the potential for publication bias
No full textWhereas delays in publication appear reasonable over a period of months, many were not published in full over a period of years and others would appear to be unlikely to ever be published. Further research should investigate the impact of publication delays on the availability of new drug treatments in clinical practic
Shortened peginterferon and ribavirin treatment for chronic hepatitis C
Full text linkBackground: Peginterferon alfa and ribavirin combination therapy is an effective treatment for many patients with chronic hepatitis C virus (HCV). Reducing the length of treatment may be advantageous. We performed a systematic review and economic evaluation to assess shorter treatment duration of this regimen.Methods: We searched fourteen bibliographic databases (including The Cochrane Library, Medline, and Embase) from 2000 to October 2009 and consulted experts and drug manufacturers. Eligible articles were randomized controlled trials (RCTs) selected according to predefined criteria. We undertook an economic evaluation to assess the cost-effectiveness of shortened treatment versus standard treatment in the UK.Results: Six trials were included. In the sub-group of patients who had low viral load (LVL) and a rapid virological response (RVR), there were no statistically significant differences in sustained virological response (SVR) rates between patients who received standard treatment (range, 83 percent to 100 percent) and those who received shortened courses (range 84 percent to 96 percent)(24 weeks for genotype 1, 16 weeks for genotype 2/3). Shortened treatment resulted in cost savings, but in some scenarios also resulted in poorer outcome, compared with standard treatment. This requires a judgment to be made on the value of the quality-adjusted life-year loss resulting from adopting a shorter treatment regimen, if shorter treatment is associated with a lower SVR than standard treatment duration.Conclusions: For chronic HCV patients who have LVL and achieve an RVR, shortened peginterferon and ribavirin combination therapy could be considered as a viable treatment option
The effectiveness of interventions to treat severe acute malnutrition in young children: a systematic review
No full textSevere acute malnutrition (SAM) arises as a consequence of a sudden period of food shortage and is associated with loss of a person’s body fat and wasting of their skeletal muscle. Many of those affected are already undernourished and are often susceptible to disease. Infants and young children are the most vulnerable as they require extra nutrition for growth and development, have comparatively limited energy reserves and depend on others. Undernutrition can have drastic and wide-ranging consequences for the child’s development and survival in the short and long term. Despite efforts made to treat SAM through different interventions and programmes, it continues to cause unacceptably high levels of mortality and morbidity. Uncertainty remains as to the most effective methods to treat severe acute malnutrition in young children.ObjectivesTo evaluate the effectiveness of interventions to treat infants and children aged < 5 years who have SAM.Data sourcesEight databases (MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CAB Abstracts Ovid, Bioline, Centre for Reviews and Dissemination, EconLit EBSCO and The Cochrane Library) were searched to 2010. Bibliographies of included articles and grey literature sources were also searched. The project expert advisory group was asked to identify additional published and unpublished references.Review methodsPrior to the systematic review, a Delphi process involving international experts prioritised the research questions. Searches were conducted and two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full texts of retrieved papers by one reviewer and checked independently by a second. Included studies were mapped to the research questions. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. Studies were synthesised through a narrative review with tabulation of the results.ResultsA total of 8954 records were screened, 224 full-text articles were retrieved, and 74 articles (describing 68 studies) met the inclusion criteria and were mapped. No evidence focused on treatment of children with SAM who were human immunodeficiency virus sero-positive, and no good-quality or adequately reported studies assessed treatments for SAM among infants < 6 months old. One randomised controlled trial investigated fluid resuscitation solutions for shock, with none adequately treating shock. Children with acute diarrhoea benefited from the use of hypo-osmolar oral rehydration solution (H-ORS) compared with the standard World Health Organization-oral rehydration solution (WHO-ORS). WHO-ORS was not significantly different from rehydration solution for malnutrition (ReSoMal), but the safety of ReSoMal was uncertain. A rice-based ORS was more beneficial than glucose-based ORSs, and provision of zinc plus a WHO-ORS had a favourable impact on diarrhoea and need for ORS. Comparisons of different diets in children with persistent diarrhoea produced conflicting findings. For treating infection, comparison of amoxicillin with ceftriaxone during inpatient therapy, and routine provision of antibiotics for 7 days versus no antibiotics during outpatient therapy of uncomplicated SAM, found that neither had a significant effect on recovery at the end of follow-up. No evidence mapped to the next three questions on factors that affect sustainability of programmes, long-term survival and readmission rates, the clinical effectiveness of management strategies for treating children with comorbidities such as tuberculosis and Helicobacter pylori infection and the factors that limit the full implementation of treatment programmes. Comparison of treatment for SAM in different settings showed that children receiving inpatient care appear to do as well as those in ambulatory or home settings on anthropometric measures and response time to treatment. Longer-term follow-up showed limited differences between the different settings. The majority of evidence on methods for correcting micronutrient deficiencies considered zinc supplements; however, trials were heterogeneous and a firm conclusion about zinc was not reached. There was limited evidence on either supplementary potassium or nicotinic acid (each produced some benefits), and nucleotides (not associated with benefits). Evidence was identified for four of the five remaining questions, but not assessed because of resource limitation.LimitationsThe systematic review focused on key questions prioritised through a Delphi study and, as a consequence, did not encompass all elements in the management of SAM. In focusing on evidence from controlled studies with the most rigorous designs that were published in the English language, the systematic review may have excluded other forms of evidence. The systematic review identified several limitations in the evidence base for assessing the effectiveness of interventions for treating young children with severe acute malnutrition, including a lack of studies assessing the different interventions; limited details of study methods used; short follow-up post intervention or discharge; and heterogeneity in participants, interventions, settings, and outcome measures affecting generalisability.ConclusionsFor many of the most highly ranked questions evidence was lacking or inconclusive. More research is needed on a range of topic areas concerning the treatment of infants and children with SAM. Further research is required on most aspects of the management of SAM in children < 5 years, including intravenous resuscitation regimens for shock, management of subgroups (e.g. infants < 6 months old, infants and children with SAM who are human immunodeficiency virus sero-positive) and on the use of antibiotics.FundingThe National Institute for Health Research Technology Assessment programme.<br/
Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation
Full text linkObjective:To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-?) for the treatment of chronic hepatitis B (CHB).Data sources:Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007.Review methods:For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-?-2a and PEG-?-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-?) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs.Results:Of the 82 papers retrieved for detailed screening, eight RCTs were included. Three evaluated ADV, four evaluated PEG-?-2b and one (from the original literature search) compared PEG-?-2b plus LAM with PEG-?-2b monotherapy. No RCTs of PEG-?-2a were identified. One ADV trial showed a statistically significant difference between ADV and placebo in terms of ALT response and HBV DNA levels, favouring ADV. Following withdrawal of ADV, levels were similar to those in placebo patients. In the ADV versus ADV plus LAM trial, there was a statistically significant difference in favour of the combination treatment. In the PEG-? trials, there were statistically significant differences favouring PEG-?-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-?-2b and IFN-? and the comparison between different staggered regimens of the commencement of PEG-?-2b and LAM, there were no statistically significant differences between groups. Four full economic evaluations were identified, in addition to one identified in the original report. Two assessed PEG-?-2a; the remainder assessed ADV. PEG-?-2a was associated with increased treatment costs and gains in quality-adjusted life expectancy. In a UK study, the incremental cost-effectiveness ratio (ICER) for PEG-?-2a was £10,444 per QALY gained compared with LAM. Evaluations of ADV found that LAM monotherapy was dominated; the ICER for ADV monotherapy compared with 'doing nothing' was $19,731. The results of the updated analysis were generally robust to changes in deterministic sensitivity analysis. In a probabilistic sensitivity analysis, the same sequence of treatments was identified as optimal. In a probabilistic sensitivity analysis, PEG-?-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of £20,000 per QALY, and 86% at a willingness-to-pay threshold of £30,000 per QALY.Conclusions:Both ADV and PEG-? are beneficial for patients with CHB in terms of suppressing viral load, reducing liver damage-associated biochemical activity, inducing HBeAg seroconversion, and reducing liver fibrosis and necroinflammation. The effects of long-term treatment with ADV are generally durable, with relatively low rates of resistance. In most cases, cost-effectiveness estimates were within acceptable ranges. Further research should assess the clinical effectiveness and cost-effectiveness of newer antiviral agents in relation to existing drugs, including the role of initiating treatment with combination therapy.<br/
The cost effectiveness of peginterferon alfa and ribavirin for the treatment of hepatitis C in children and young people
No full textOBJECTIVES: To assess the cost-effectiveness of peginterferon ?-2a and peginterferon ?-2b in combination with ribavirin compared to best supportive care (BSC), for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3 to 17 years. METHODS: A Markov state-transition economic model of chronic HCV in children and young people was developed that extrapolated the impact of sustained virological response (SVR) on life expectancy, quality-adjusted life expectancy and lifetime costs. The model was adapted from one previously developed for adults. A systematic review was conducted of the clinical effectiveness of the treatments, and the health related quality of life for patients with hepatitis C. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS: Seven studies were identified that were relatively small and of generally poor quality. Estimates of SVR were similar for for peginterferon ?-2a (60%) and peginterferon ?-2b (58%) was similar, whilst the SVR for no treatment was assumed to be zero. From this model, peginterferon alfa (?-2a or ?-2b) in combination with ribavirin was more effective and cheaper than BSC. Sensitivity analyses suggest that the results were generally robust to all changes to the structural assumptions and input parameters. The model results were most sensitive to changes to the discount rate, time horizon, SVR and baseline fibrosis of the cohort. CONCLUSIONS: Treatment of children and young people with peginterferon alfa (?-2a or ?-2b) and ribavirin may be an effective therapy. Peginterferon alfa (?-2a or ?-2b) in combination with ribavirin is cost-effective compared with BSC. However, the available evidence is of poor quality. The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the UK HTA programme or Department of Health
Infliximab for the treatment of adults with psoriasis. Evidence Review Group Report for NICE's Single Technology Appraisal process
No full textThis paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of infliximab for the treatment of moderate to severe plaque psoriasis, in accordance with the licensed indication, based on the evidence submission from Schering-Plough to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer's definition of the decision problem were severity [Psoriasis Area and Severity Index (PASI) score], remission rates, relapse rates and health-related quality of life. The main evidence in the submission comes from four randomised controlled trials (RCT) comparing infliximab with placebo and eight RCTs comparing either etanercept or efalizumab with placebo. At week 10, patients on infliximab had a significantly higher likelihood of attaining a reduction in PASI score than placebo patients. There were also statistically significant differences between infliximab and placebo in the secondary outcomes. In the comparator trials both the efalizumab and etanercept arms included a significantly higher proportion of patients who achieved a reduction in PASI score at week 12 than the placebo arms. No head-to-head studies were identified directly comparing infliximab with etanercept or efalizumab. The manufacturer carried out an indirect comparison, but the ERG had reservations about the comparison because of the lack of information presented and areas of uncertainty in relation to the included data. The economic model presented by the manufacturer was appropriate for the disease area and given the available data. The cost-effectiveness analysis estimates the mean length of time that an individual would respond to infliximab compared with continuous etanercept and the utility gains associated with this response. The base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with continuous etanercept for patients with severe psoriasis was £26,095 per quality-adjusted life-year. A one-way sensitivity analysis, a scenario analysis and a probabilistic sensitivity analysis were undertaken by the ERG. The ICER is highly sensitive to assumptions about the costs and frequency of inpatient stays for non-responders of infliximab. The guidance issued by NICE in August 2007 as a result of the STA states that infliximab within its licensed indication is recommended for the treatment of adults with very severe plaque psoriasis, or with psoriasis that has failed to respond to standard systematic therapies. Infliximab treatment should be continued beyond 10 weeks in people whose psoriasis has shown an adequate response to treatment within 10 weeks. In addition, when using the Dermatology Life Quality Index (DLQI), care should be taken to take into account the patient's disabilities, to ensure DLQI continues to be an accurate measure
Using process data to understand outcomes in sexual health promotion: an example from a review of school-based programmes to prevent sexually transmitted infections
No full textThis article discusses how process indicators can complement outcomes as part of a comprehensive explanatory evaluation framework, using the example of skills-based behavioural interventions to prevent sexually transmitted infections and promote sexual health among young people in schools. A systematic review was conducted, yielding 12 eligible outcome evaluations, 9 of which included a process evaluation. There were few statistically significant effects in terms of changes in sexual behaviour outcomes, but statistically significant effects were more common for knowledge and self-efficacy. Synthesis of the findings of the process evaluations identified a range of factors that might explain outcomes, and these were organized into two overarching categories: the implementation of interventions, and student engagement and intervention acceptability. Factors which supported implementation and engagement and acceptability included good quality teacher training, involvement and motivation of key school stakeholders and relevance and appeal to young people. Factors which had a negative impact included teachers’ failure to comprehend the theoretical basis for behaviour change, school logistical problems and omission of topics that young people considered important. It is recommended that process indicators such as these be assessed in future evaluations of school-based sexual health behavioural interventions, as part of a logic model
Training teachers for the public health workforce: systematic mapping and synthesis of effectiveness and processes
No full textBackground: Schools are an important setting for health promotion, and teachers have an integral role in promoting children's and young people's health and wellbeing. Adequate initial teacher training and continuing professional development in health is therefore important, and trainers need sound evidence of effectiveness. However, the evidence base for teacher training is broad and has not been subjected to systematic review. The aim of this project was to assess the key characteristics of this evidence base and to investigate effectiveness and associated processes.Methods: A novel methodological approach was used: a systematic map of the key characteristics of studies (stage 1) followed by a detailed synthesis of a subset of mapped studies (stage 2). A sensitive search was done on 20 bibliographic databases including Medline, Embase, ERIC, and PsychINFO. Reference lists of existing studies were checked and relevant websites were searched to identify unpublished work. Each study meeting the stage 1 inclusion criteria was mapped by a reviewer applying a keyword method devised for this study. Keywords described study characteristics such as country, health topic area, teaching qualification status (eg, pre-service, in-service), training content and format, and processes and outcomes examined. To be included in the map, studies had to report teacher training about health, be an outcome or process assessment or a survey, and be published after 1990. The map results were presented to a multidisciplinary advisory group. Through structured discussion, the group prioritised studies focusing on initial teacher training for stage 2. A standardised data extraction template was then applied to stage 2. Methodological quality and risk of bias was assessed unmasked with published critical appraisal criteria. Data extraction and quality assessment were done by one reviewer and checked by a second.Findings: We screened 16,620 references, of which 170 were mapped (stage 1). Studies were undertaken in Europe, Africa, Asia, Australia, South America, and the Middle East, with a predominance of studies from the USA (42%). Common topics included sexual and reproductive health (22%), drugs and alcohol (18%), and mental and emotional health (16%). A range of study types were used, including outcome assessments (73%, of which 56% were controlled trials), process assessments (46%), and surveys (11%). Factual information about health (77%) and the development of skills for promoting health (66%) were common. Of the studies focusing on initial teacher training (n=20, stage 2), most were in the UK or Australia. They covered a range of topics including general health promotion, child protection, and mental health. 12 studies reported outcomes (most were before and after single cohort designs), 19 reported processes, and eight reported both. After training there were increases in trainee teachers' knowledge of health, and confidence to teach personal, social, health, and economic education. Trainees also felt better able to identify and manage child protection issues and children with mental and emotional health problems. No studies reported outcomes for pupils. In general, training was acceptable to trainees. Trainees' views on the adequacy of the training varied, with some reporting that they did not feel prepared to deal with issues such as child protection on entering the early teaching career period. The evidence suggested that for training to meet trainee teachers' needs, it may need to include practical experience and skills, be personally relevant and take into account individual needs, and relate to teachers' practice in schools.Interpretation: The evidence base for teacher training in health is diverse and of variable quality. Some positive effects on teachers' knowledge and confidence are evident. However, there is a scarcity of research on school pupils' health and educational outcomes. Further assessment of health-related training spanning initial teacher training and the early career years is needed.Funding: National Institute for Health Research Public Health Research programme (09/3005/12).<br/
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