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The Cochrane Database of Systematic... Dec 2013Fibromyalgia is characterized by chronic widespread pain that leads to reduced physical function. Exercise training is commonly recommended as a treatment for management... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibromyalgia is characterized by chronic widespread pain that leads to reduced physical function. Exercise training is commonly recommended as a treatment for management of symptoms. We examined the literature on resistance training for individuals with fibromyalgia. Resistance training is exercise performed against a progressive resistance with the intention of improving muscle strength, muscle endurance, muscle power, or a combination of these.
OBJECTIVES
To evaluate the benefits and harms of resistance exercise training in adults with fibromyalgia. We compared resistance training versus control and versus other types of exercise training.
SEARCH METHODS
We searched nine electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, PEDro, Dissertation Abstracts, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform, AMED) and other sources for published full-text articles. The date of the last search was 5 March 2013. Two review authors independently screened 1856 citations, 766 abstracts and 156 full-text articles. We included five studies that met our inclusion criteria.
SELECTION CRITERIA
Selection criteria included: a) randomized clinical trial, b) diagnosis of fibromyalgia based on published criteria, c) adult sample, d) full-text publication, and e) inclusion of between-group data comparing resistance training versus a control or other physical activity intervention.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently assessed risk of bias and extracted intervention and outcome data. We resolved disagreements between the two review authors and questions regarding interpretation of study methods by discussion within the pairs or when necessary the issue was taken to the full team of 11 members. We extracted 21 outcomes of which seven were designated as major outcomes: multidimensional function, self reported physical function, pain, tenderness, muscle strength, attrition rates, and adverse effects. We evaluated benefits and harms of the interventions using standardized mean differences (SMD) or mean differences (MD) or risk ratios or Peto odds ratios and 95% confidence intervals (CI). Where two or more studies provided data for an outcome, we carried out a meta-analysis.
MAIN RESULTS
The literature search yielded 1865 citations with five studies meeting the selection criteria. One of the studies that had three arms contributed data for two comparisons. In the included studies, there were 219 women participants with fibromyalgia, 95 of whom were assigned to resistance training programs. Three randomized trials compared 16 to 21 weeks of moderate- to high-intensity resistance training versus a control group. Two studies compared eight weeks of progressive resistance training (intensity as tolerated) using free weights or body weight resistance exercise versus aerobic training (ie, progressive treadmill walking, indoor and outdoor walking), and one study compared 12 weeks of low-intensity resistance training using hand weights (1 to 3 lbs (0.45 to 1.36 kg)) and elastic tubing versus flexibility exercise (static stretches to major muscle groups).Statistically significant differences (MD; 95% CI) favoring the resistance training interventions over control group(s) were found in multidimensional function (Fibromyalgia Impact Questionnaire (FIQ) total decreased 16.75 units on a 100-point scale; 95% CI -23.31 to -10.19), self reported physical function (-6.29 units on a 100-point scale; 95% CI -10.45 to -2.13), pain (-3.3 cm on a 10-cm scale; 95% CI -6.35 to -0.26), tenderness (-1.84 out of 18 tender points; 95% CI -2.6 to -1.08), and muscle strength (27.32 kg force on bilateral concentric leg extension; 95% CI 18.28 to 36.36).Differences between the resistance training group(s) and the aerobic training groups were not statistically significant for multidimensional function (5.48 on a 100-point scale; 95% CI -0.92 to 11.88), self reported physical function (-1.48 units on a 100-point scale; 95% CI -6.69 to 3.74) or tenderness (SMD -0.13; 95% CI -0.55 to 0.30). There was a statistically significant reduction in pain (0.99 cm on a 10-cm scale; 95% CI 0.31 to 1.67) favoring the aerobic groups.Statistically significant differences were found between a resistance training group and a flexibility group favoring the resistance training group for multidimensional function (-6.49 FIQ units on a 100-point scale; 95% CI -12.57 to -0.41) and pain (-0.88 cm on a 10-cm scale; 95% CI -1.57 to -0.19), but not for tenderness (-0.46 out of 18 tender points; 95% CI -1.56 to 0.64) or strength (4.77 foot pounds torque on concentric knee extension; 95% CI -2.40 to 11.94). This evidence was classified low quality due to the low number of studies and risk of bias assessment. There were no statistically significant differences in attrition rates between the interventions. In general, adverse effects were poorly recorded, but no serious adverse effects were reported. Assessment of risk of bias was hampered by poor written descriptions (eg, allocation concealment, blinding of outcome assessors). The lack of a priori protocols and lack of care provider blinding were also identified as methodologic concerns.
AUTHORS' CONCLUSIONS
The evidence (rated as low quality) suggested that moderate- and moderate- to high-intensity resistance training improves multidimensional function, pain, tenderness, and muscle strength in women with fibromyalgia. The evidence (rated as low quality) also suggested that eight weeks of aerobic exercise was superior to moderate-intensity resistance training for improving pain in women with fibromyalgia. There was low-quality evidence that 12 weeks of low-intensity resistance training was superior to flexibility exercise training in women with fibromyalgia for improvements in pain and multidimensional function. There was low-quality evidence that women with fibromyalgia can safely perform moderate- to high-resistance training.
Topics: Adult; Exercise; Female; Fibromyalgia; Humans; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 24362925
DOI: 10.1002/14651858.CD010884 -
Nutrients Sep 2023(1) Background: There has been a growing interest in understanding the causes of obesity and developing effective prevention strategies. Lifestyle change programs are... (Review)
Review
(1) Background: There has been a growing interest in understanding the causes of obesity and developing effective prevention strategies. Lifestyle change programs are often considered the gold standard for weight reduction, and they can help individuals with obesity achieve an annual weight loss of around 8-10%. The aim of this review was to evaluate the effect of food during the winter holidays. This knowledge will serve as a valuable foundation for the development of targeted interventions and prevention programs. (2) Methods: We conducted a systematic search of the literature via one database (PubMed). The search was limited to studies published in English in the last 10 years, with adult participants, but without specifying limits regarding the study design. We excluded articles that addressed intermittent fasting diets or weight loss intervention methods during the holidays through various diets. (3) In separate sections, we analyzed the psychological causes of gaining weight during the winter holidays, behavioral patterns, prevention strategies and the nutritional composition of the different types of food served during the festive period. Results: Using the combination of the terms "holiday and obesity", "holiday and weight gain", "festive season and obesity", and "festive season and weight gain" we obtained 216 results involving the addressed topic. Thus, only ten articles remained after screening, with a total of 4627 participants. Most participants experienced weight fluctuations during the study period, particularly during holidays. One concerning observation was that most of the weight gained during these periods was maintained even after the end of the studies, especially in those with obesity. A supervised exercise program and a controlled diet at work over the Christmas period are effective strategies for avoiding weight gain and its deleterious effects in people with metabolic syndrome or weight problems. (4) In addition, attention must be focused on the psycho-social factors during the holidays because for some people it is a stressful period and can cause a much higher caloric consumption. The simplest method to approach during the holidays is to implement small tips and tricks during this period that will prevent individuals from gaining extra pounds. Conclusions: It is essential to acknowledge that obesity is a multifaceted condition that requires a comprehensive and multidisciplinary approach to address its underlying factors and provide ongoing assistance to individuals in their weight-management endeavors. Even the most effective short-term interventions are likely to produce continued positive outcomes with persistent intervention and support.
Topics: Adult; Humans; Holidays; Seasons; Obesity; Weight Gain; Feeding Behavior; Weight Loss
PubMed: 37836485
DOI: 10.3390/nu15194201 -
American Journal of Clinical Dermatology May 2023Hidradenitis suppurativa affects up to 4% of the population worldwide. Many treatment options exist but these come with a significant side-effect profile. Exercise,...
BACKGROUND
Hidradenitis suppurativa affects up to 4% of the population worldwide. Many treatment options exist but these come with a significant side-effect profile. Exercise, weight loss, and dietary modifications may be simple inexpensive alternatives and/or adjuncts to treating this disease.
OBJECTIVES
We aimed to summarize published evidence on the effects of dietary, weight loss, and exercise interventions on the clinical course, severity, or subjective improvement of hidradenitis suppurativa and to provide a framework regarding dietary changes and exercise modalities for clinicians treating this disease.
METHODS
A literature search of Scopus (1993 onwards), PubMed (1986 onwards), and MEDLINE (OVID interface, 1946 onwards) was conducted on 22 October, 2022. Case-control studies, cohort studies, and randomized controlled trials with five or more subjects conducted on adult participants (aged >18 years) were included; case reports, case series, and review papers were excluded.
RESULTS
Fifteen studies involving 2829 patients were included, encompassing nine cohort studies, five cross-sectional studies, and one cross-over study. Patients who were female, lost more than 50 pounds (22.7 kg), or were obese prior to weight loss saw improvement in hidradenitis suppurativa severity with weight loss. There was evidence for beneficial effects of diets, such as the Mediterranean diet that minimizes sugar, highly processed carbohydrates, and dairy, and emphasizes chicken, fruits, and vegetables, in patients with hidradenitis suppurativa. Evidence also supported benefit from oral zinc and vitamin D supplementation.
CONCLUSIONS
More evidence is needed in the form of randomized controlled trials or well-designed controlled trials to evaluate the effect of exercise and dietary manipulation on the hidradenitis suppurativa disease course. Overall, there is significant but weak evidence to support improvement in hidradenitis suppurativa severity with weight loss, dietary changes, and micronutrient supplementation. There is no significant evidence to support improvement in hidradenitis suppurativa symptomology with any type of exercise intervention.
CLINICAL TRIAL REGISTRATION
This protocol was registered with PROSPERO with the registration number CRD4202235099.
Topics: Humans; Female; Male; Hidradenitis Suppurativa; Cross-Over Studies; Cross-Sectional Studies; Diet; Weight Loss
PubMed: 36757580
DOI: 10.1007/s40257-023-00756-w -
Health Technology Assessment... 2003To establish the clinical and cost-effectiveness of amantadine, oseltamivir and zanamivir compared to standard care for the treatment and prevention of influenza. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To establish the clinical and cost-effectiveness of amantadine, oseltamivir and zanamivir compared to standard care for the treatment and prevention of influenza.
DATA SOURCES
Electronic databases. Reference lists of identified articles and key publications. Relevant trials.
REVIEW METHODS
A systematic review and meta-analysis of the randomised evidence was undertaken to investigate the effectiveness of oseltamivir and zanamivir compared to standard care for treatment and prophylaxis use for influenza A and B. An additional systematic review of the effectiveness of amantadine for treatment and prophylaxis use for influenza A in children and the elderly was also undertaken. Economic decision models were constructed to examine the cost-effectiveness and cost-utility of the alternative strategies for treating and preventing influenza A and/or B. This was informed by the systematic reviews outlined above and additional sources of information where required.
RESULTS
The systematic review of the treatment of influenza found that oseltamivir reduced the median duration of symptoms in the influenza positive group by 1.38 days for the otherwise healthy adult population, 0.5 day for the high-risk population, and 1.5 days for the children population. This compared to 1.26 days, 1.99 days, and 1.3 for the similar groups for inhaled zanamivir. The systematic review of the prevention of influenza found that the relative risk reduction for oseltamivir was between approximately 75 and 90% and approximately 70 and 90% for inhaled zanamivir depending on the strategy adopted and the population under consideration. For the economic model a base case was constructed that focussed primarily on the health benefits generated by shortening the period of influenza illness. This base case found that, compared to standard care, the estimated cost per quality-adjusted life year ranged from pound 6190 to pound 31,529 for healthy adults, from pound 4535 to pound 22,502 for the 'high-risk' group, from pound 6117 to pound 30,825 for children, and from pound 5057 to pound 21,781 for the residential care elderly population. The base case model included valuations of the health effects of pneumonia (and otitis media in the children's model) based on observed rates in the trials. However it does not include the cost of hospitalisations as only very limited data was available for the effects of antivirals on hospitalisation rates. As for mortality rates, deaths from influenza were rare in trials of neuraminidase inhibitors (NIs). Therefore, suitable data on mortality were not available from these sources. As avoided hospitalisation costs and avoided mortality are potentially important we also carried out sensitivity analysis that involved extrapolating the observed reductions in pneumonias in the NI trials to hospitalisations and deaths. In all four models the cost-effectiveness of NIs is substantially improved by this extrapolation. For prophylaxis, antiviral drugs were compared with vaccination as preventative strategies. In all cases the cost-effectiveness ratios for vaccination were either low or cost-saving. In the base case the cost-effectiveness of antivirals was relatively unfavourable, there were scenarios relating to the elderly residential care model where antivirals as an additional strategy could be cost-effective.
CONCLUSIONS
The cost-effectiveness varies markedly between the intervention strategies and target populations. The estimate of cost effectiveness is also sensitive to variations in certain key parameters of the model, for example the proportion of all influenza-like illnesses that are influenza. The effectiveness literature that was used to inform the economic decision model spans many decades and hence great caution should be exercised when interpreting the results of indirect intervention comparisons from the model. Further randomised trials making direct comparisons would be valuable to verify the model's findings.
Topics: Antiviral Agents; Cost-Benefit Analysis; Decision Support Techniques; Humans; Influenza Vaccines; Influenza, Human; Quality-Adjusted Life Years; Treatment Outcome
PubMed: 14609480
DOI: 10.3310/hta7350 -
Health Technology Assessment... Aug 2010To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling.
DATA SOURCES
The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database.
STUDY SELECTION
The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI.
DATA EXTRACTION
Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person.
RESULTS
Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions.
LIMITATIONS
Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies.
CONCLUSIONS
More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.
Topics: Adrenergic Uptake Inhibitors; Biofeedback, Psychology; Cost-Benefit Analysis; Electric Stimulation Therapy; Exercise Therapy; Female; Humans; Life Style; Markov Chains; Models, Economic; Pelvic Floor; Quality-Adjusted Life Years; Risk Factors; Selective Serotonin Reuptake Inhibitors; Stress, Psychological; Suburethral Slings; Treatment Outcome; United Kingdom; Urinary Incontinence, Stress
PubMed: 20738930
DOI: 10.3310/hta14400 -
Health Technology Assessment... 2001The prevalence of obesity in developed societies is increasing. Obesity is associated with an increased risk of co-morbidity, including cardiovascular disease and... (Review)
Review
BACKGROUND
The prevalence of obesity in developed societies is increasing. Obesity is associated with an increased risk of co-morbidity, including cardiovascular disease and diabetes. Following the withdrawal of fenfluramine and dexfenfluramine, interest has focused on a novel anti-obesity drug orlistat.
OBJECTIVE
To systematically assess the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity. METHODS - SEARCH STRATEGY: Nineteen electronic databases were searched from inception to June 2000. Additionally, Internet searches were carried out, bibliographies of retrieved articles were examined and submissions were received from the manufacturer of orlistat. METHODS - INCLUSION AND EXCLUSION CRITERIA: Randomised controlled trials (RCTs) evaluating the effectiveness of orlistat used for weight loss or maintenance of weight loss in overweight or obese patients were eligible for inclusion. Primary outcome measures were changes in body weight, fat content or fat distribution. Secondary outcomes were changes in obesity-related risk-factor profiles, such as lipid levels, indicators of glycaemic control and blood pressure. Studies recruiting people with eating disorders such as anorexia nervosa and bulimia nervosa were excluded. METHODS - PROCESS OF STUDY SELECTION: Assessment of titles and abstracts was performed independently by two reviewers. If either reviewer considered a reference to be relevant, the full paper was retrieved. Full papers were assessed against the review selection criteria by two independent reviewers, and disagreements were resolved through discussion. METHODS - DATA EXTRACTION: Data were extracted by one reviewer into structured summary tables and checked by a second reviewer. Any disagreements about data were resolved by discussion. METHODS - QUALITY ASSESSMENT: Each included trial was assessed against a comprehensive checklist for methodological quality. Quality assessment was performed independently by two reviewers with disagreements resolved by discussion. METHODS - METHODS OF ANALYSIS/SYNTHESIS: This report is a narrative summary, with results grouped according to study endpoint. Statistical pooling was undertaken in groups of trials that were considered to be sufficiently similar. METHODS - ESTIMATION OF QUALITY OF LIFE, COSTS AND COST-EFFECTIVENESS AND/OR COST PER QUALITY-ADJUSTED LIFE-YEAR: Relevant economic evaluations were identified from the search strategy described above. Assessment of methodological quality was undertaken using principles outlined in published guidelines. METHODS - COMPANY SUBMISSIONS: Data from company submissions were subject to the same selection and appraisal processes as other studies considered for inclusion in the review, except that only RCTs with a duration of at least 1 year were selected. RESULTS - RESULTS OF THE SEARCH STRATEGY: Fourteen RCTs (including three company submissions) and two economic evaluations (including one company submission) were included in the review. RESULTS - RESULTS OF THE QUALITY ASSESSMENT: Methodological quality of trials was moderate to good. The main problems were lack of detail on methods used to produce true randomisation, small sample sizes in some cases and failure to use intention-to-treat analysis. It is likely that maintenance of blinding was difficult due to adverse effects associated with the study medication. RESULTS - EVIDENCE OF CLINICAL EFFECTIVENESS AND COST-EFFECTIVENESS: Most of the trials showed greater weight loss and better weight maintenance with orlistat compared to placebo at all endpoints (statistically significant differences for both outcomes). Orlistat 120 mg three times daily was the optimum regimen in terms of weight loss. Most trials showed significant improvement in at least some lipid concentration parameters, and, in three RCTs, orlistat produced statistically significant reductions in blood pressure relative to placebo. In obese patients with type 2 diabetes, orlistat resulted in a significantly greater weight loss at 1 year compared with placebo, and some parameters of glycaemic control and lipid concentration also showed significantly greater improvements compared with placebo. The incidence of gastrointestinal adverse events was consistently higher in orlistat groups compared with placebo, and orlistat use was associated with lower serum levels of fat-soluble vitamins. The cost per quality-adjusted life-year for orlistat was 45,881 UK pounds. CONCLUSIONS - IMPLICATIONS FOR CLINICAL PRACTICE: Although many trials have demonstrated statistically significant differences between groups in terms of weight loss in favour of orlistat versus placebo, the differences may not always be of clinical significance. The clinical significance of between-group differences for secondary outcomes may also be debatable. Possible adverse effects should be taken into account when prescribing orlistat, particularly gastrointestinal effects. (ABSTRACT TRUNCATED)
Topics: Anti-Obesity Agents; Cost-Benefit Analysis; Drug Evaluation; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Technology Assessment, Biomedical; Treatment Outcome; United Kingdom
PubMed: 11399238
DOI: 10.3310/hta5180 -
Harm Reduction Journal Nov 2021Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting... (Review)
Review
Reporting and methodological quality of systematic literature reviews evaluating the associations between e-cigarette use and cigarette smoking behaviors: a systematic quality review.
INTRODUCTION
Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting quality have not yet been assessed. This systematic quality review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2 to evaluate the quality of systematic reviews investigating potential associations between e-cigarette use and cigarette smoking.
MATERIALS AND METHODS
PubMed/MEDLINE, Embase, and PsycINFO were searched from 01 January 2007 to 24 June 2020. Methodological quality was assessed using AMSTAR 2, and reporting quality was assessed using PRISMA guidelines.
RESULTS
Of 331 potentially relevant systematic reviews, 20 met predefined inclusion criteria. Most reviews (n = 15; 75%) reported on e-cigarette use and cigarette smoking cessation, while three reported on e-cigarette use and cigarette smoking initiation (15%); and two reported on cigarette smoking initiation and cessation (10%). According to AMSTAR 2 guidelines, 18 of the 20 reviews (90%) were "critically low" in overall confidence of the results, while two were ranked "low." Additionally, reporting quality varied across the reviews, with only 60% reporting at least half of the PRISMA items.
DISCUSSION
Methodological limitations were identified across reviews examining potential associations between e-cigarette use and cigarette smoking behaviors, indicating that findings from these reviews should be interpreted with caution.
CONCLUSIONS
Future systematic reviews in this field should strive to adhere to AMSTAR 2 and PRISMA guidelines, to provide high quality syntheses of the available data with transparent and complete reporting.
Topics: Cigarette Smoking; Electronic Nicotine Delivery Systems; Humans; Research Report; Vaping
PubMed: 34838030
DOI: 10.1186/s12954-021-00570-9 -
Health Technology Assessment... 2001Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the... (Comparative Study)
Comparative Study Review
BACKGROUND
Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the early stages of the disease, most cases are not detected until the advanced stages. Consequently, the prognosis after diagnosis is poor and the 5-year survival rate in the UK is only about 30%. Current recommendations suggest that first-line chemotherapy for ovarian cancer should involve paclitaxel and platinum (Pt)-based therapy (cisplatin/ carboplatin), however, most patients develop resistant or refractory disease and require second-line therapy. Patients may respond to re-challenge with Pt-agents if the treatment-free interval is > 6 months, but an alternative is often required. Topotecan is one of six drugs currently licensed in the UK for second-line therapy, and recent reviews suggest that it has modest efficacy in the treatment of advanced disease and performs favourably against paclitaxel. However, these reviews are based on a limited number of reports mainly consisting of non-randomised Phase I and II studies.
OBJECTIVES OF THE REVIEW
To examine the clinical effectiveness and cost-effectiveness of oral and intravenous topotecan (Hycamtin, SmithKline Beecham, UK) for the treatment of all stages of ovarian cancer.
SEARCH STRATEGY
Sixteen electronic databases from inception to September 2000 and Internet resources were searched, in addition to the bibliographies of retrieved articles and submissions from pharmaceutical companies.
INCLUSION AND EXCLUSION CRITERIA
Two reviewers independently screened all titles/abstracts and included/excluded studies based on full copies of manuscripts. Any disagreements were resolved through discussion. Only randomised controlled trials (RCTs) and full economic evaluations comparing topotecan to non-topotecan regimens were included. All stages of therapy and disease were considered, and the outcomes included were survival, response, symptom relief, quality of life, adverse effects and costs.
METHODS
DATA EXTRACTION STRATEGY: Data were extracted into an Access database by one reviewer and checked by a second. Any disagreements were resolved through discussion.
METHODS
QUALITY ASSESSMENT STRATEGY: Two reviewers, using specified criteria, independently assessed the quality of the clinical effectiveness studies and the economic evaluations. Any disagreements were resolved through discussion.
METHODS
ANALYSIS STRATEGY: Due to the limited number of studies included in the review and the fact that they compared topotecan with different comparators, the out-come data could not be pooled statistically. Clinical effectiveness data are discussed separately under the different outcome subheadings. For time-to-event data, hazard ratios with 95% confidence intervals are presented where available, and for the remaining outcomes, relative risks are reported or calculated where sufficient data were available. Relative risk data are also presented in the form of Forest plots without pooled estimates. Economic data are presented in the form of a summary and critique of the evidence, and a grading (A-I) assigned to each study indicating the direction and magnitude of the cost-effectiveness data.
INCLUDED STUDIES
A total of 568 titles/abstracts were identified and screened for relevance. Full copies of 72 papers were assessed and seven published manuscripts reporting details of two studies of clinical effectiveness and one economic evaluation were included. Further details of the two clinical effectiveness studies and two new economic evaluations were identified from confidential company submissions. Overall, two international multicentre RCTs of effectiveness comparing topotecan with paclitaxel (trial 039) and topotecan with caelyx (trial 30-49) were included in the review. The three economic evaluations included in the review comprised one cost-minimisation analysis (CMA) comparing topotecan with caelyx, one cost-consequences analysis (CCA) comparing topotecan with paclitaxel, etoposide and altretamine and one cost-effectiveness analysis (CEA) comparing topotecan with paclitaxel.
RESULTS
QUALITY OF CLINICAL EFFECTIVENESS DATA: Both clinical effectiveness studies (trial 30-49 and 039) were of reasonable quality, although it was unclear whether either performed valid intention-to-treat analyses. In addition, trial 30-49 failed to state whether the outcome assessors were blinded to treatment allocation. RESULTS --QUALITY OF ECONOMIC EVALUATIONS: The CCA (comparing topotecan with three comparators) was of poor quality and of little relevance to the UK NHS. The CMA and CEA were of reasonable quality overall and relevant to the UK NHS. However, both, in particular the CEA, suffered from methodological problems, and thus their findings should be interpreted with caution.
RESULTS
ASSESSMENT OF CLINICAL EFFECTIVENESS: The assessment of clinical effectiveness was based on limited data. Only two trials with a total of 709 participants were identified. In general, with a few minor exceptions, there were no statistically significant differences between topotecan and paclitaxel, or topotecan and caelyx in survival, response rate, median time to response, median duration of response and quality of life. Significant differences that were reported were mainly identified in subgroup analyses (Pt-sensitive disease and disease without ascites) of questionable validity and their relevance to a general advanced ovarian cancer patient population undergoing second-line chemotherapy is unclear. However, statistically significant differences were observed in the incidence of adverse effects. Topotecan was associated with increased incidences of haematological toxicities (including neutropenia, leukopenia, anaemia and thrombocytopenia), alopecia, nausea and vomiting. Caelyx-treated patients suffered from significantly increased incidences of Palmar-Plantar erythrodysesthesia, stomatitis, mucous membrane disorders and skin rashes. Paclitaxel was associated with significant increases in alopecia, arthralgia, myalgia, neuropathy, paraesthesiae, skeletal pain and flushing.
RESULTS
ASSESSMENT OF COST-EFFECTIVENESS: The assessment of cost-effectiveness was also based on limited data, with three evaluations identified, one of which was not relevant. The two remaining studies, comparing topotecan with paclitaxel (CEA) and topotecan with caelyx (CMA), both used effectiveness data from multicentre RCTs and based their costs on 1999/2000 UK sources. The evaluations were conducted from a UK NHS perspective and findings presented in GB pounds/Euros. Topotecan for the second-line treatment of advanced ovarian cancer was shown to be more cost-effective than paclitaxel (32,513 GB pounds versus 46,186 GB pounds per person in terms of any response (complete or partial), incremental cost-effectiveness = 3065 GB pounds) in all respects except cost per time without toxicity or symptoms, but less cost-effective than caelyx (14,023 GB pounds versus 9979 GB pounds per person regardless of whether the patient responded). However, direct comparisons of the cost findings between the two studies is difficult because they used different designs, different time horizons for the cost analyses and the findings were presented as costs per person for only patients who responded in one study (topotecan versus paclitaxel) and costs per person regardless of whether they responded in the other study (topotecan versus caelyx).
CONCLUSIONS
This review indicates that there is little evidence in the form of RCTs on which to base an assessment of the effectiveness of topotecan as second-line therapy for advanced ovarian cancer. The evidence suggests there were no statistically significant differences overall between topotecan and paclitaxel, or topotecan and caelyx in clinical outcomes. However, statistically significant differences were observed in the incidence of adverse effects. The clinical significance of the findings is not discussed. Overall, the effects of topotecan could at best be described as modest, but the alternative agents offer no real advantages except fewer side-effects and possibly improved cost-effectiveness. Both of the clinical effectiveness studies on which this evidence is based had methodological flaws, the most serious being the lack of a blinded assessor in the topotecan versus caelyx trial, which is important for unbiased assessment of response outcomes. The economic evaluations also suffered from a number of potential problems.
CONCLUSIONS
RECOMMENDATIONS FOR RESEARCH: Further good quality RCTs and CEAs are required comparing topotecan with other licensed and potentially useful (soon to be licensed) second-line treatments for ovarian cancer. At present, it is difficult to make any decisions about topotecan and other drugs for second-line therapy without good quality direct comparisons. In view of the ongoing studies identified, an update of the current review should be considered in approximately 18 months (Summer 2002) or possibly sooner if the recently commissioned National Institute for Clinical Excellence review of caelyx for ovarian cancer identifies additional data relevant to topotecan.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Female; Humans; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Technology Assessment, Biomedical; Topotecan
PubMed: 11701100
DOI: 10.3310/hta5280 -
Health Technology Assessment... Mar 2007To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals.
DATA SOURCES
Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed.
REVIEW METHODS
The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective.
RESULTS
Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-dose strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behaviour and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was pound 12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was pound 30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was pound 13,697/QALY, for BMT versus no drug therapy that the ICER was pound 26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses.
CONCLUSIONS
Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models.
Topics: Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Female; Heroin Dependence; Humans; Male; Methadone
PubMed: 17313907
DOI: 10.3310/hta11090 -
Health Technology Assessment... May 2004To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder. (Review)
Review
A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder.
OBJECTIVES
To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder.
DATA SOURCES
Electronic databases; industry submissions made to the National Institute for Clinical Excellence.
REVIEW METHODS
Randomised trials and economic evaluations that evaluated the effectiveness of quetiapine, olanzapine or valproate semisodium in the treatment of mania associated with bipolar disorder were selected for inclusion. Data were extracted by one reviewer into a Microsoft Access database and checked for quality and accuracy by a second. The quality of the cost-effectiveness studies was assessed using a checklist updated from that developed by Drummond and colleagues. Relative risk and mean difference data were presented as Forest plots but only pooled where this made sense clinically and statistically. Studies were grouped by drug and, within each drug, by comparator used. Chi-squared tests of heterogeneity were performed for the outcomes if pooling was indicated. A probabilistic model was developed to estimate costs from the perspective of the NHS, and health outcomes in terms of response rate, based on an improvement of at least 50% in a patient's baseline manic symptoms derived from an interview-based mania assessment scale. The model evaluated the cost-effectiveness of the alternative drugs when used as part of treatment for the acute manic episode only.
RESULTS
Eighteen randomised trials met the inclusion criteria. Aspects of three of the quetiapine studies were commercial-in-confidence. The quality of the included trials was limited and overall, key methodological criteria were not met in most trials. Quetiapine, olanzapine and valproate semisodium appear superior to placebo in reducing manic symptoms, but may cause side-effects. There appears to be little difference between these treatments and lithium in terms of effectiveness, but quetiapine is associated with somnolence and weight gain, whereas lithium is associated with tremor. Olanzapine as adjunct therapy to mood stabilisers may be more effective than placebo in reducing mania and improving global health, but it is associated with more dry mouth, somnolence, weight gain, increased appetite, tremor and speech disorder. There was little difference between these treatments and haloperidol in reducing mania, but haloperidol was associated with more extrapyramidal side-effects and negative implications for health-related quality of life. Intramuscular olanzapine and lorazepam were equally effective and safe in one very short (24 hour) trial. Valproate semisodium and carbamazepine were equally effective and safe in one small trial in children. Olanzapine may be more effective than valproate semisodium in reducing mania, but was associated with more dry mouth, increased appetite, oedema, somnolence, speech disorder, Parkinson-like symptoms and weight gain. Valproate semisodium was associated with more nausea than olanzapine. The results from the base-case analysis demonstrate that choice of optimal strategy is dependent on the maximum that the health service is prepared to pay per additional responder. For a figure of less than 7179 British pounds per additional responder, haloperidol is the optimal decision; for a spend in excess of this, it would be olanzapine. Under the most favourable scenario in relation to the costs of responders and non-responders beyond the 3-week period considered in the base-case analysis, the incremental cost-effectiveness ratio of olanzapine is reduced to 1236 British pounds.
CONCLUSIONS
In comparison with placebo, quetiapine, olanzapine and valproate semisodium appear superior in reducing manic symptoms, but all drugs are associated with adverse events. In comparison with lithium, no significant differences were found between the three drugs in terms of effectiveness, and all were associated with adverse events. Several limitations of the cost-effectiveness analysis exist, which inevitably means that the results should be treated with some caution. There remains a need for well-conducted, randomised, double-blind head-to-head comparisons of drugs used in the treatment of mania associated with bipolar disorder and their cost-effectiveness. Participant demographic, diagnostic characteristics, the treatment of mania in children, the use of adjunctive therapy and long-term safety issues in the elderly population, and acute and long-term treatment are also subjects for further study.
Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 15147609
DOI: 10.3310/hta8190