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The Cochrane Database of Systematic... Mar 2016All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect.
PRIMARY OBJECTIVES
To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).
SECONDARY OBJECTIVES
To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction.
SEARCH METHODS
We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015).
SELECTION CRITERIA
Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of heterogeneity.
MAIN RESULTS
After updating the literature search, which was extended to include four new weight-reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual-care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by -2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): -4.0 to -0.9 mm Hg) and diastolic blood pressure by -1.9 mm Hg (MD; 95% CI: -3.0 to -0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure.
AUTHORS' CONCLUSIONS
In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long-term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long-term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Pressure; Cyclobutanes; Diet, Reducing; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Rimonabant; Safety-Based Drug Withdrawals; Time; Topiramate; Weight Loss
PubMed: 26934640
DOI: 10.1002/14651858.CD007654.pub4 -
The Cochrane Database of Systematic... Jun 2017Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). However, it is still questionable if eradication of hepatitis C virus in the blood eliminates hepatitis C in the body, and improves survival and leads to fewer complications.
OBJECTIVES
To assess the benefits and harms of DAAs in people with chronic HCV.
SEARCH METHODS
We searched for all published and unpublished trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.
SELECTION CRITERIA
Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C-related morbidity, serious adverse events, and quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and sustained virological response. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight-step procedure to assess thresholds for statistical and clinical significance. The overall quality of the evidence was evaluated using GRADE.
MAIN RESULTS
We included a total of 138 trials randomising a total of 25,232 participants. The 138 trials assessed the effects of 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty-four trials involved DAAs on the market or under development (13,466 participants). Fifty-seven trials administered withdrawn or discontinued DAAs. Trial participants were treatment-naive (95 trials), treatment-experienced (17 trials), or both treatment-naive and treatment-experienced (24 trials). The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.Meta-analysis of the effects of all DAAs on the market or under development showed no evidence of a difference when assessing hepatitis C-related morbidity or all-cause mortality (OR 3.72, 95% CI 0.53 to 26.18, P = 0.19, I² = 0%, 2,996 participants, 11 trials, very low-quality evidence). As there were no data on hepatitis C-related morbidity and very few data on mortality (DAA 15/2377 (0.63%) versus control 1/617 (0.16%)), it was not possible to perform Trial Sequential Analysis on hepatitis C-related morbidity or all-cause mortality.Meta-analysis of all DAAs on the market or under development showed no evidence of a difference when assessing serious adverse events (OR 0.93, 95% CI 0.75 to 1.15, P = 0.52, I² = 0%, 15,817 participants, 43 trials, very low-quality evidence). The Trial Sequential Analysis showed that the cumulative Z-score crossed the trial sequential boundary for futility, showing that there was sufficient information to rule out that DAAs compared with placebo reduced the relative risk of a serious adverse event by 20%. The only DAA that showed a significant difference on risk of serious adverse events when meta-analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20%, and when one trial with an extreme result was excluded, then the meta-analysis result showed no evidence of a difference.DAAs on the market or under development seemed to reduce the risk of no sustained virological response (RR 0.44, 95% CI 0.37 to 0.52, P < 0.00001, I² = 77%, 6886 participants, 32 trials, very low-quality evidence) and Trial Sequential Analysis confirmed this meta-analysis result.Only 1/84 trials on the market or under development assessed the effects of DAAs on health-related quality of life (SF-36 mental score and SF-36 physical score).Withdrawn or discontinued DAAs had no evidence of a difference when assessing hepatitis C-related morbidity and all-cause mortality (OR 0.64, 95% CI 0.23 to 1.79, P = 0.40, I² = 0%; 5 trials, very low-quality evidence). However, withdrawn DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73, P = 0.001, I² = 0%, 29 trials, very low-quality evidence), and Trial Sequential Analysis confirmed this meta-analysis result.Most of all outcome results were short-term results; therefore, we could neither confirm nor reject any long-term effects of DAAs. None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).
AUTHORS' CONCLUSIONS
Overall, DAAs on the market or under development do not seem to have any effects on risk of serious adverse events. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.
Topics: Antiviral Agents; Cause of Death; Hepacivirus; Hepatitis C, Chronic; Humans; Nucleic Acid Synthesis Inhibitors; Placebos; Protease Inhibitors; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Simeprevir
PubMed: 28585310
DOI: 10.1002/14651858.CD012143.pub2 -
The Cochrane Database of Systematic... Sep 2017Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials that have validated that usage.
OBJECTIVES
To assess the benefits and harms of DAAs in people with chronic HCV.
SEARCH METHODS
We searched for all published and unpublished trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.
SELECTION CRITERIA
Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C-related morbidity, serious adverse events, and health-related quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and SVR. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight-step procedure to assess thresholds for statistical and clinical significance. We evaluated the overall quality of the evidence, using GRADE.
MAIN RESULTS
We included a total of 138 trials randomising a total of 25,232 participants. The trials were generally short-term trials and designed primarily to assess the effect of treatment on SVR. The trials evaluated 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty-four trials involved DAAs on the market or under development (13,466 participants). Fifty-seven trials administered DAAs that were discontinued or withdrawn from the market. Study populations were treatment-naive in 95 trials, had been exposed to treatment in 17 trials, and comprised both treatment-naive and treatment-experienced individuals in 24 trials. The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.We could not reliably determine the effect of DAAs on the market or under development on our primary outcome of hepatitis C-related morbidity or all-cause mortality. There were no data on hepatitis C-related morbidity and only limited data on mortality from 11 trials (DAA 15/2377 (0.63%) versus control 1/617 (0.16%); OR 3.72, 95% CI 0.53 to 26.18, very low-quality evidence). We did not perform Trial Sequential Analysis on this outcome.There is very low quality evidence that DAAs on the market or under development do not influence serious adverse events (DAA 5.2% versus control 5.6%; OR 0.93, 95% CI 0.75 to 1.15 , 15,817 participants, 43 trials). The Trial Sequential Analysis showed that there was sufficient information to rule out that DAAs reduce the relative risk of a serious adverse event by 20% when compared with placebo. The only DAA that showed a lower risk of serious adverse events when meta-analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20%, and when one trial with an extreme result was excluded, the meta-analysis result showed no evidence of a difference.DAAs on the market or under development may reduce the risk of no SVR from 54.1% in untreated people to 23.8% in people treated with DAA (RR 0.44, 95% CI 0.37 to 0.52, 6886 participants, 32 trials, low quality evidence). Trial Sequential Analysis confirmed this meta-analysis result.Only 1/84 trials on the market or under development assessed the effects of DAAs on health-related quality of life (SF-36 mental score and SF-36 physical score).There was insufficient evidence from trials on withdrawn or discontinued DAAs to determine their effect on hepatitis C-related morbidity and all-cause mortality (OR 0.64, 95% CI 0.23 to 1.79; 5 trials, very low-quality evidence). However, these DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73; 29 trials, very low-quality evidence). Trial Sequential Analysis confirmed this meta-analysis result.None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).
AUTHORS' CONCLUSIONS
The evidence for our main outcomes of interest come from short-term trials, and we are unable to determine the effect of long-term treatment with DAAs. The rates of hepatitis C morbidity and mortality observed in the trials are relatively low and we are uncertain as to how DAAs affect this outcome. Overall, there is very low quality evidence that DAAs on the market or under development do not influence serious adverse events. There is insufficient evidence to judge if DAAs have beneficial or harmful effects on other clinical outcomes for chronic HCV. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs may reduce the number of people with detectable virus in their blood, but we do not have sufficient evidence from randomised trials that enables us to understand how SVR affects long-term clinical outcomes. SVR is still an outcome that needs proper validation in randomised clinical trials.
Topics: Antiviral Agents; Cause of Death; Hepacivirus; Hepatitis C, Chronic; Humans; Nucleic Acid Synthesis Inhibitors; Placebos; Protease Inhibitors; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Simeprevir
PubMed: 28922704
DOI: 10.1002/14651858.CD012143.pub3 -
The Cochrane Database of Systematic... Mar 2012Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been used to reduce the high rate of death by severe sepsis or septic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been used to reduce the high rate of death by severe sepsis or septic shock. This is an update of a Cochrane review (originally published in 2007 and updated in 2008).
OBJECTIVES
We assessed the clinical effectiveness and safety of APC for the treatment of patients with severe sepsis or septic shock.
SEARCH METHODS
For this updated review we searched CENTRAL (The Cochrane Library 2010, Issue 6); MEDLINE (1966 to June 2010); EMBASE (1980 to July 1, 2010); BIOSIS (1965 to July 1, 2010); CINAHL (1982 to 16 June 2010) and LILACS (1982 to 16 June 2010). There was no language restriction.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) assessing the effects of APC for severe sepsis in adults and children. We excluded studies on neonates. We considered all-cause mortality at day 28, at the end of study follow up, and hospital mortality as the primary outcomes.
DATA COLLECTION AND ANALYSIS
We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We used a random-effects model.
MAIN RESULTS
We identified one new RCT in this update. We included a total of five RCTs involving 5101 participants. For 28-day mortality, APC did not reduce the risk of death in adult participants with severe sepsis (pooled RR 0.97, 95% confidence interval (CI) 0.78 to 1.22; P = 0.82, I(2) = 68%). APC use was associated with an increased risk of bleeding (RR 1.47, 95% CI 1.09 to 2.00; P = 0.01, I(2) = 0%). In paediatric patients, APC did not reduce the risk of death (RR 0.98, 95% CI 0.66 to 1.46; P = 0.93). Although the included trials had no major limitations most of them modified their original completion or recruitment protocols.
AUTHORS' CONCLUSIONS
This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. Additionally, APC is associated with a higher risk of bleeding. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC.Warning: On October 25th 2011, the European Medicines Agency issued a press release on the worldwide withdrawal of Xigris (activated protein C / drotrecogin alfa) from the market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the PROWESS-SHOCK study. Furthermore, Eli Lily has announced the discontinuation of all other ongoing clinical trials. The final results of the PROWESS-SHOCK study are expected to be published in 2012. This systematic review will be updated when results of the PROWESS-SHOCK or other trials are published.
Topics: Adult; Age Factors; Anti-Infective Agents; Cause of Death; Child; Drug Recalls; Early Termination of Clinical Trials; Hospital Mortality; Humans; Protein C; Randomized Controlled Trials as Topic; Recombinant Proteins; Sepsis; Shock, Septic
PubMed: 22419295
DOI: 10.1002/14651858.CD004388.pub5 -
PloS One 2013Standardised or 'plain' tobacco packaging was introduced in Australia in December 2012 and is currently being considered in other countries. The primary objective of... (Review)
Review
Is consumer response to plain/standardised tobacco packaging consistent with framework convention on tobacco control guidelines? A systematic review of quantitative studies.
BACKGROUND AND OBJECTIVES
Standardised or 'plain' tobacco packaging was introduced in Australia in December 2012 and is currently being considered in other countries. The primary objective of this systematic review was to locate, assess and synthesise published and grey literature relating to the potential impacts of standardised tobacco packaging as proposed by the guidelines for the international Framework Convention on Tobacco Control: reduced appeal, increased salience and effectiveness of health warnings, and more accurate perceptions of product strength and harm.
METHODS
Electronic databases were searched and researchers in the field were contacted to identify studies. Eligible studies were published or unpublished primary research of any design, issued since 1980 and concerning tobacco packaging. Twenty-five quantitative studies reported relevant outcomes and met the inclusion criteria. A narrative synthesis was conducted.
RESULTS
Studies that explored the impact of package design on appeal consistently found that standardised packaging reduced the appeal of cigarettes and smoking, and was associated with perceived lower quality, poorer taste and less desirable smoker identities. Although findings were mixed, standardised packs tended to increase the salience and effectiveness of health warnings in terms of recall, attention, believability and seriousness, with effects being mediated by the warning size, type and position on pack. Pack colour was found to influence perceptions of product harm and strength, with darker coloured standardised packs generally perceived as containing stronger tasting and more harmful cigarettes than fully branded packs; lighter coloured standardised packs suggested weaker and less harmful cigarettes. Findings were largely consistent, irrespective of location and sample.
CONCLUSIONS
The evidence strongly suggests that standardised packaging will reduce the appeal of packaging and of smoking in general; that it will go some way to reduce consumer misperceptions regarding product harm based upon package design; and will help make the legally required on-pack health warnings more salient.
Topics: Adolescent; Adult; Attitude to Health; Databases, Bibliographic; Female; Harm Reduction; Health Knowledge, Attitudes, Practice; Humans; Male; Marketing; Motivation; Product Labeling; Smoking; Smoking Cessation; Tobacco Products
PubMed: 24146791
DOI: 10.1371/journal.pone.0075919 -
British Journal of Haematology Nov 2013Evidence regarding the efficacy of gemtuzumab ozogamicin (GO) addition to standard induction chemotherapy in newly diagnosed acute myeloid leukaemia (AML) is... (Meta-Analysis)
Meta-Analysis Review
Evidence regarding the efficacy of gemtuzumab ozogamicin (GO) addition to standard induction chemotherapy in newly diagnosed acute myeloid leukaemia (AML) is conflicting. This systematic review aimed to identify and summarize all evidence regarding the benefits and harms of adding GO to conventional chemotherapy for induction treatment of AML. A comprehensive literature search of two databases (PUBMED and Cochrane) from inception up to November 22, 2012, and 4 years of proceedings from four major haematology/oncology conferences was undertaken. Endpoints included benefits (complete remission, relapse-free, event-free, and overall survival), and harms (early mortality and incidence of hepatic veno-occlusive disease/sinusoidal obstructive syndrome). Seven trials (3942 patients) met all inclusion criteria. Addition of GO showed improved relapse-free [Hazard Ratio (HR) = 0·84 (95% confidence interval (CI) 0·71-0·99)] and event-free survival [HR = 0·59 (95%CI 0·48-0·74)] but not overall survival [HR = 0·95 (95%CI 0·83-1·08)]. Addition of GO resulted in higher rate of early mortality [Risk Ratio = 1·60 (95%CI 1·07-2·39)]. Improved overall survival was observed in studies using a lower cumulative GO dose (<6 mg/m(2) ) [HR = 0·89 (95%CI 0·81-0·99)]. Addition of GO to conventional chemotherapy as induction therapy may improve relapse-free and event-free survival, but does not impact overall survival and significantly increases early mortality in AML.
Topics: Aminoglycosides; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Evidence-Based Medicine; Gemtuzumab; Hepatic Veno-Occlusive Disease; Humans; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Randomized Controlled Trials as Topic; Remission Induction; Safety-Based Drug Withdrawals; Survival Analysis; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 24033280
DOI: 10.1111/bjh.12528 -
The Cochrane Database of Systematic... Jul 2017Urinary incontinence has been shown to affect up to 50% of women. Studies in the USA have shown that up to 80% of these women have an element of stress urinary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urinary incontinence has been shown to affect up to 50% of women. Studies in the USA have shown that up to 80% of these women have an element of stress urinary incontinence. This imposes significant health and economic burden on society and the women affected. Colposuspension and now mid-urethral slings have been shown to be effective in treating patients with stress incontinence. However, associated adverse events include bladder and bowel injury, groin pain and haematoma formation. This has led to the development of third-generation single-incision slings, also referred to as mini-slings.It should be noted that TVT-Secur (Gynecare, Bridgewater, NJ, USA) is one type of single-incision sling; it has been withdrawn from the market because of poor results. However, it is one of the most widely studied single-incision slings and was used in several of the trials included in this review. Despite its withdrawal from clinical use, it was decided that data pertaining to this sling should be included in the first iteration of this review, so that level 1a data are available in the literature to confirm its lack of efficacy.
OBJECTIVES
To assess the effectiveness of mini-sling procedures in women with urodynamic clinical stress or mixed urinary incontinence in terms of improved continence status, quality of life or adverse events.
SEARCH METHODS
We searched: Cochrane Incontinence Specialised Register (includes: CENTRAL, MEDLINE, MEDLINE In-Process) (searched 6 February 2013); ClinicalTrials.gov, WHO ICTRP (searched 20 September 2012); reference lists.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials in women with urodynamic stress incontinence, symptoms of stress incontinence or stress-predominant mixed urinary incontinence, in which at least one trial arm involves one of the new single-incision slings. The definition of a single-incision sling is "a sling that does not involve either a retropubic or transobturator passage of the tape or trocar and involves only a single vaginal incision (i.e. no exit wounds in the groin or lower abdomen)."
DATA COLLECTION AND ANALYSIS
Three review authors assessed the methodological quality of potentially eligible trials and independently extracted data from individual trials.
MAIN RESULTS
We identified 31 trials involving 3290 women. Some methodological flaws were observed in some trials; a summary of these is given in the 'Risk of bias in included studies' section.No studies compared single-incision slings versus no treatment, conservative treatment, colposuspension, laparoscopic procedures or traditional sub-urethral slings. No data on the comparison of single-incision slings versus retropubic mid-urethral slings (top-down approach) were available, but the review authors believe this did not affect the overall comparison versus retropubic mid-urethral slings.Types of single-incision slings included in this review: TVT-Secur (Gynecare); MiniArc (American Medical Systems, Minnetonka, USA); Ajust (CR Bard Inc., Covington, USA); Needleless (Mayumana Healthcare, Lisse, The Netherlands); Ophira (Promedon, Cordoba, Argentina); Tissue Fixation System (TFS PTY Ltd, Sydney, Australia) and CureMesh (DMed Co. Inc., Seoul, Korea).Women were more likely to remain incontinent after surgery with single-incision slings than with retropubic slings such as tension-free vaginal tape (TVT) (121/292, 41% vs 72/281, 26%; risk ratio (RR) 2.08, 95% confidence interval (CI) 1.04 to 4.14). Duration of the operation was slightly shorter for single-incision slings but with higher risk of de novo urgency (RR 2.39, 95% CI 1.25 to 4.56). Four of five studies in the comparison included TVT-Secur as the single-incision sling.Single-incision slings resulted in higher incontinence rates compared with inside-out transobturator slings (30% vs 11%; RR 2.55, 95% CI 1.93 to 3.36). The adverse event profile was significantly worse, specifically consisting of higher risks of vaginal mesh exposure (RR 3.75, 95% CI 1.42 to 9.86), bladder/urethral erosion (RR 17.79, 95% CI 1.06 to 298.88) and operative blood loss (mean difference 18.79, 95% CI 3.70 to 33.88). Postoperative pain was less common with single-incision slings (RR 0.29, 95% CI 0.20 to 0.43), and rates of long-term pain or discomfort were marginally lower, but the clinical significance of these differences is questionable. Most of these findings were derived from the trials involving TVT-Secur: Excluding the other trials showed that high risk of incontinence was principally associated with use of this device (RR 2.65, 95% CI 1.98 to 3.54). It has been withdrawn from clinical use.Evidence was insufficient to reveal a difference in incontinence rates with other single-incision slings compared with inside-out or outside-in transobturator slings. Duration of the operation was marginally shorter for single-incision slings compared with transobturator slings, but only by approximately two minutes and with significant heterogeneity in the comparison. Risks of postoperative and long-term groin/thigh pain were slightly lower with single-incision slings, but overall evidence was insufficient to suggest a significant difference in the adverse event profile for single-incision slings compared with transobturator slings. Evidence was also insufficient to permit a meaningful sensitivity analysis of the other single-incision slings compared with transobturator slings, as all confidence intervals were wide. The only significant differences were observed in rates of postoperative and long-term pain, and in duration of the operation, which marginally favoured single-incision slings.Overall results show that TVT-Secur is considerably inferior to retropubic and inside-out transobturator slings, but additional evidence is required to allow any reasonable comparison of other single-incision slings versus transobturator slings.When one single-incision sling was compared with another, evidence was insufficient to suggest a significant difference between any of the slings in any of the comparisons made.
AUTHORS' CONCLUSIONS
TVT-Secur is inferior to standard mid-urethral slings for the treatment of women with stress incontinence and has already been withdrawn from clinical use. Not enough evidence has been found on other single-incision slings compared with retropubic or transobturator slings to allow reliable comparisons. A brief economic commentary (BEC) identified two studies which reported no difference in clinical outcomes between single-incision slings and transobturator mid-urethral slings, but single-incision slings may be more cost-effective than transobturator mid-urethral slings based on one-year follow-up. Additional adequately powered and high-quality trials with longer-term follow-up are required. Trials should clearly describe the fixation mechanism of these single-incisions slings: It is apparent that, although clubbed together as a single group, a significant difference in fixation mechanisms may influence outcomes.
Topics: Female; Humans; Prosthesis Failure; Randomized Controlled Trials as Topic; Safety-Based Medical Device Withdrawals; Suburethral Slings; Urinary Incontinence; Urologic Surgical Procedures
PubMed: 28746980
DOI: 10.1002/14651858.CD008709.pub3 -
Expert Opinion on Drug Safety Jan 2018Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain... (Review)
Review
INTRODUCTION
Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. .
AREAS COVERED
We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler's Side Effects of Drugs; Stephens' Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions.
EXPERT OPINION
Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.
Topics: Adverse Drug Reaction Reporting Systems; Analgesics; Guidelines as Topic; Humans; Pain; Pharmacovigilance; Product Surveillance, Postmarketing; Safety-Based Drug Withdrawals
PubMed: 29076385
DOI: 10.1080/14740338.2018.1398232 -
Medicina (Kaunas, Lithuania) Jul 2020Since silicone breast implants were introduced to the market several decades ago, the safety of breast implants has remained controversial. Recently, several studies...
Since silicone breast implants were introduced to the market several decades ago, the safety of breast implants has remained controversial. Recently, several studies have explored breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) and breast implant illness (BII). Several countries have developed national breast implant registries to improve the safety and quality of breast implant surgery. We performed a systematic review of the current status of national breast implant registries and propose a pilot form of an appropriate breast implant registry model for Korea. The systematic review was conducted in accordance with the "preferred reporting items for systematic reviews and meta-analyses (PRISMA) pro forma". PubMed and Google Scholar databases were searched to identify all articles containing information on national breast implant registries. We limited the search to articles written in the English language from 2010 to 2020. Articles were reviewed by two independent authors. A total of 63 articles related to national breast implant registries, registry principles and national breast implant registry annual reports were identified. After reviewing the literature, 25 national breast implant registry-related articles were included in the full-text synthesis. Currently, four countries, The Netherlands, Australia, Sweden, and the UK, have breast implant registries with well-formed sources for big data. Overall, similarities in data points were detected for three categories: implant-related complications, operation details, and device information. However, there were differences for each registry in terms of governance, funding, and capture rate. After reviewing other countries' experiences, tentative datasets for the Korean Breast Implant Registry (K-BIR) were developed. The K-BIR can improve the quality of breast implant surgery in Korea by providing datasets on overall processes and outcome measures with quality indicators and risk adjustment factors. This approach will register characteristics of patients and monitor breast implants, complications, and surgical procedures to improve the outcomes of breast implant surgery in Korea. In addition, it can be used as a track-and-trace system with automated notifications to patients in the event of a product recall or other safety concerns related to a specific type of implant.
Topics: Adult; Australia; Austria; Breast Implantation; Breast Implants; Equipment and Supplies; Female; Humans; Postoperative Complications; Registries; Treatment Outcome; United States
PubMed: 32718052
DOI: 10.3390/medicina56080370 -
The Cochrane Database of Systematic... Oct 2009Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke in a study of secondary prevention of adenoma recurrence. Further information is available at www.vioxx.com.Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor previously licensed for treating acute and chronic pain; it was associated with fewer gastrointestinal adverse events than conventional NSAIDs. An earlier Cochrane review (Barden 2005) showed that rofecoxib is at least as effective as conventional non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of rofecoxib in single oral doses for moderate and severe postoperative pain.
SEARCH STRATEGY
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009.
SELECTION CRITERIA
Randomised, double blind, placebo-controlled trials of single dose orally administered rofecoxib in adults with moderate to severe acute postoperative pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected.
MAIN RESULTS
Twenty new studies and seven from the earlier review met the inclusion criteria. Twenty-four studies were in dental surgery and three in other types of surgery. In total, 2636 participants were treated with rofecoxib 50 mg, 20 with rofecoxib 500 mg, and 1251 with placebo. The NNT for at least 50% pain relief over 4 to 6 hours with rofecoxib 50 mg was 2.2 (2.0 to 2.3) in all studies combined, 1.9 (1.8 to 2.0) in dental studies, and 6.8 (4.6 to 13) in other types of surgery. The median time to use of rescue medication was 14 hours for rofecoxib 50 mg and 2 hours for placebo. Significantly fewer participants used rescue medication following rofecoxib 50 mg than with placebo. Adverse events did not differ from placebo.
AUTHORS' CONCLUSIONS
Rofecoxib 50 mg (two to four times the standard daily dose for chronic pain) is an effective single dose oral analgesic for acute postoperative pain in adults, with a relatively long duration of action.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Humans; Lactones; Pain, Postoperative; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Sulfones
PubMed: 19821329
DOI: 10.1002/14651858.CD004604.pub3