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Preventive Medicine Reports Jan 2024Cannabis legalization provides an opportunity to communicate with consumers through mandated health warnings on cannabis packaging. However, research on cannabis health... (Review)
Review
BACKGROUND
Cannabis legalization provides an opportunity to communicate with consumers through mandated health warnings on cannabis packaging. However, research on cannabis health warnings is a nascent field. Therefore, a review is needed to synthesize cannabis health warning research and inform ongoing policy discussions.
METHODS
This paper used systematic review guidelines to search online databases, including PubMed Central, Scopus, Web of Science, Jstor, Communication and Mass Media Complete, Medline, PsycINFO, and Google Scholar. Search strings combined the terms "cannabis" or "marijuana" with "health warning" or "health warning message" or "warning label" or "health warning label" or "health information label." Results were synthesized narratively.
RESULTS
The search identified 90 research articles. After screening, 17 studies on the impact of cannabis health warnings were retained. Retained studies focused on the hypothetical effects of cannabis health warnings ( = 11; 64.7 %) and "real world" effects of implementing warnings post-legalization ( = 6; 35.3 %). Evidence indicated mandated cannabis health warnings improved noticing and recall of health warning content. Cannabis health warnings describing risks of addiction were consistently rated the least effective. Pictorial cannabis health warnings generally outperformed text-only warnings when displayed on their own, while experiments with warnings on products had mixed results. Cannabis health warnings decreased product appeal, mainly when package branding was minimized.
CONCLUSIONS
Health warnings on cannabis packaging are an important strategy to communicate risk to consumers. Mandating warnings increased notice, recall, and health knowledge. Warnings with pictures and describing specific risks were most effective, as was showing warnings without product branding.
PubMed: 38222305
DOI: 10.1016/j.pmedr.2023.102573 -
PloS One 2022We conducted a scoping systematic review with respect to how consumer engagement with interactive advertising is evaluated and if interactive features influence consumer...
We conducted a scoping systematic review with respect to how consumer engagement with interactive advertising is evaluated and if interactive features influence consumer recall, awareness, or comprehension of product claims and risk disclosures for informing regulatory science. MEDLINE, PsycINFO, Business Source Corporate, and SCOPUS were searched for original research published from 1997 through February 2021. Two reviewers independently screened titles/abstracts and full-text articles for inclusion. Outcomes were abstracted into a structured abstraction form. We included 32 studies overall. The types of interactive ads evaluated included website banner and pop up ads, search engine ads, interactive TV ads, advergames, product websites, digital magazine ads, and ads on social network sites. Twenty-three studies reported objective measures of engagement using observational analyses or laboratory-based experiments. In nine studies evaluating the association between different interactivity features and outcomes, the evidence was mixed on whether more interactivity improves or worsens recall and comprehension. Studies vary with respect to populations, designs, ads evaluated, and outcomes assessed.
Topics: Advertising; Community Participation; Consumer Behavior; Disclosure; Health Education; Humans; Mental Recall
PubMed: 35113964
DOI: 10.1371/journal.pone.0263339 -
The Cochrane Database of Systematic... Jan 2021This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.
OBJECTIVES
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 and diastolic blood pressure, and on body weight reduction.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.
SELECTION CRITERIA
Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.
MAIN RESULTS
This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.
AUTHORS' CONCLUSIONS
In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Bias; Blood Pressure; Body Weight; Bupropion; Diet, Reducing; Drug Combinations; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Naltrexone; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Time; Topiramate
PubMed: 33454957
DOI: 10.1002/14651858.CD007654.pub5 -
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 -
Journal of Biomaterials Applications Feb 2020Medical devices made of polydioxanone (a synthetic biodegradable polymer) have been available since the early 1980s. However, no review regarding their performance and...
BACKGROUND
Medical devices made of polydioxanone (a synthetic biodegradable polymer) have been available since the early 1980s. However, no review regarding their performance and safety has been published.
OBJECTIVE
This systematic review intends to review and assess commercially available polydioxanone implants and their safety and performance in patients.
METHODS
We searched for approved polydioxanone implants in several Food and Drug Administration databases. Then, we performed a literature search for publications and clinical trials where polydioxanone devices were implanted in patients. This search was performed on MEDLINE, Embase, Scopus and other databases. Safety and performance of polydioxanone implants in patients were assessed and compared with the implantation of non-polydioxanone devices, when possible, based on scoring systems developed by the authors that analyse surgical site infection rates, inflammatory reaction rates, foreign body response, postoperative pain and fever.
RESULTS
Food and Drug Administration databases search revealed that 48 implants have been approved since 1981, with 1294 adverse reactions or product malfunction in the last decade and 16 recalls. A total of 49 clinical trials and 104 scientific publications were found. Polydioxanone sutures and meshes/plates had low rates of surgical site infection, inflammatory reaction, foreign body response and postoperative fever. Polydioxanone clips/staples reported high rates of surgical site infection, postoperative fever and pain, with sub-optimal clinical performance and poor safety rates. The remaining implants identified showed high levels of safety and performance. Safety scores of polydioxanone implants and non-polydioxanone alternatives are similar. Polydioxanone monofilament sutures perform better than non-polydioxanone alternatives but performance did not differ with remaining polydioxanone implant types.
CONCLUSIONS
Although polydioxanone clips/staples should be implanted with caution and monitored carefully, in general, safety and performance scores of other polydioxanone implants did not differ from non-polydioxanone alternatives. This review will be a useful reference for researchers and industries developing new polydioxanone medical devices.
Topics: Absorbable Implants; Biocompatible Materials; Device Approval; Humans; Inflammation; Medical Device Recalls; Polydioxanone
PubMed: 31771403
DOI: 10.1177/0885328219888841 -
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... 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 -
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 -
BMC Medicine Nov 2016We identified anti-obesity medications withdrawn since 1950 because of adverse drug reactions after regulatory approval, and examined the evidence used to support such... (Review)
Review
BACKGROUND
We identified anti-obesity medications withdrawn since 1950 because of adverse drug reactions after regulatory approval, and examined the evidence used to support such withdrawals, investigated the mechanisms of the adverse reactions, and explored the trends over time.
METHODS
We conducted searches in PubMed, the World Health Organization database of drugs, the websites of drug regulatory authorities, and selected full texts, and we hand searched references in retrieved documents. We included anti-obesity medications that were withdrawn between 1950 and December 2015 and assessed the levels of evidence used for making withdrawal decisions using the Oxford Centre for Evidence-Based Medicine criteria.
RESULTS
We identified 25 anti-obesity medications withdrawn between 1964 and 2009; 23 of these were centrally acting, via monoamine neurotransmitters. Case reports were cited as evidence for withdrawal in 80% of instances. Psychiatric disturbances, cardiotoxicity (mainly attributable to re-uptake inhibitors), and drug abuse or dependence (mainly attributable to neurotransmitter releasing agents) together accounted for 83% of withdrawals. Deaths were reportedly associated with seven products (28%). In almost half of the cases, the withdrawals occurred within 2 years of the first report of an adverse reaction.
CONCLUSIONS
Most of the drugs that affect monoamine neurotransmitters licensed for the treatment of obesity over the past 65 years have been withdrawn because of adverse reactions. The reasons for withdrawal raise concerns about the wisdom of using pharmacological agents that target monoamine neurotransmitters in managing obesity. Greater transparency in the assessment of harms from anti-obesity medications is therefore warranted.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Obesity; Product Surveillance, Postmarketing; Safety-Based Drug Withdrawals
PubMed: 27894343
DOI: 10.1186/s12916-016-0735-y -
Tobacco Regulatory Science Oct 2016In this paper we synthesize the evidence from eye tracking research in tobacco control to inform tobacco regulatory strategies and tobacco communication campaigns.
OBJECTIVE
In this paper we synthesize the evidence from eye tracking research in tobacco control to inform tobacco regulatory strategies and tobacco communication campaigns.
METHODS
We systematically searched 11 databases for studies that reported eye tracking outcomes in regards to tobacco regulation and communication. Two coders independently reviewed studies for inclusion and abstracted study characteristics and findings.
RESULTS
Eighteen studies met full criteria for inclusion. Eye tracking studies on health warnings consistently showed these warnings often were ignored, though eye tracking demonstrated that novel warnings, graphic warnings, and plain packaging can increase attention toward warnings. Eye tracking also revealed that greater visual attention to warnings on advertisements and packages consistently was associated with cognitive processing as measured by warning recall.
CONCLUSIONS
Eye tracking is a valid indicator of attention, cognitive processing, and memory. The use of this technology in tobacco control research complements existing methods in tobacco regulatory and communication science; it also can be used to examine the effects of health warnings and other tobacco product communications on consumer behavior in experimental settings prior to the implementation of novel health communication policies. However, the utility of eye tracking will be enhanced by the standardization of methodology and reporting metrics.
PubMed: 27668270
DOI: 10.18001/TRS.2.4.9