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The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
BMC Health Services Research Dec 2019In the original publication of this article [1], one author's name needs to be revised from Pavaneh Isfahani to Parvaneh Isfahani.
In the original publication of this article [1], one author's name needs to be revised from Pavaneh Isfahani to Parvaneh Isfahani.
PubMed: 31822274
DOI: 10.1186/s12913-019-4766-x -
European Journal of Clinical... Nov 2019Poorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and...
BACKGROUND
Poorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and Replication (TIDieR) checklist was developed to improve the reporting of active interventions. The extent to which TIDieR has been used to improve description of placebo or sham control is not known.
MATERIALS AND METHODS
We systematically identified and examined all placebo/sham-controlled randomised trials published in 2018 in the top six general medical journals. We reported how many of the TIDieR checklist items were used to describe the placebo/sham control(s). We supplemented this with a sample of 100 placebo/sham-controlled trials from any journal and searched Google Scholar to identify placebo/sham-controlled trials citing TIDieR.
RESULTS
We identified 94 placebo/sham-controlled trials published in the top journals in 2018. None reported using TIDieR, and none reported placebo or sham components completely. On average eight TIDieR items were addressed, with placebo/sham control name (100%) and when and how much was administered (97.9%) most commonly reported. Some items (rationale, 8.5%, whether there were modifications, 25.5%) were less often reported. In our sample of less well-cited journals, reporting was poorer (average of six items) and followed a similar pattern. Since TIDieR's first publication, six placebo-controlled trials have cited it according to Google Scholar. Two of these used the checklist to describe placebo controls; neither one completely desribed the placebo intervention.
CONCLUSIONS
Placebo and sham controls are poorly described within randomised trials, and TIDieR is rarely used to guide these descriptions. We recommend developing guidelines to promote better descriptions of placebo/sham control components within clinical trials.
Topics: Checklist; Control Groups; Humans; Placebos; Randomized Controlled Trials as Topic; Research Report
PubMed: 31519047
DOI: 10.1111/eci.13169 -
Administration and Policy in Mental... Jan 2020Inadequate implementation strategy reporting restricts research synthesis and replicability. We explored the implementation strategy reporting quality of a sample of...
Inadequate implementation strategy reporting restricts research synthesis and replicability. We explored the implementation strategy reporting quality of a sample of mental health articles using Proctor et al.'s (Implement Sci 8:139, 2013) reporting recommendations. We conducted a narrative review to generate the sample of articles and assigned a reporting quality score to each article. The mean article reporting score was 54% (range 17-100%). The most reported domains were: name (100%), action (82%), target (80%), and actor (67%). The least reported domains included definition (6%), temporality (26%), justification (34%), and outcome (37%). We discuss limitations and provide recommendations to improve reporting.
Topics: Evidence-Based Practice; Health Plan Implementation; Humans; Implementation Science; Mental Health; Research
PubMed: 31482489
DOI: 10.1007/s10488-019-00965-8 -
Competition and price among brand-name drugs in the same class: A systematic review of the evidence.PLoS Medicine Jul 2019Some experts have proposed combating rising drug prices by promoting brand-brand competition, a situation that is supposed to arise when multiple US Food and Drug...
BACKGROUND
Some experts have proposed combating rising drug prices by promoting brand-brand competition, a situation that is supposed to arise when multiple US Food and Drug Administration (FDA)-approved brand-name products in the same class are indicated for the same condition. However, numerous reports exist of price increases following the introduction of brand-name competition, suggesting that it may not be effective. We performed a systematic literature review of the peer-reviewed health policy and economics literature to better understand the interplay between new drug entry and intraclass drug prices.
METHODS AND FINDINGS
We searched PubMed and EconLit for original studies on brand-brand competition in the US market published in English between January 1990 and April 2019. We performed a qualitative synthesis of each study's data, recording its primary objective, methodology, and results. We found 10 empirical investigations, with 1 study each on antihypertensives, anti-infectives, central nervous system stimulants for attention deficit/hyperactivity disorder, disease-modifying therapies for multiple sclerosis, histamine-2 (H2) blockers, and tumor necrosis factor (TNF) inhibitors; 2 studies on cancer medications; and 2 studies on all marketed or new drugs. None of the studies reported that brand-brand competition lowers list prices of existing drugs within a class. The findings of 2 studies suggest that such competition may help restrain how new drug prices are set. Other studies found evidence that brand-brand competition was mediated by the relative quality of competing drugs and the extent to which they are marketed, with safer or more effective new drugs and greater marketing associated with higher intraclass list prices. Our investigation was limited by the studies' use of list rather than net prices and the age of some of the data.
CONCLUSIONS
Our findings suggest that policies to promote brand-brand competition in the US pharmaceutical market, such as accelerating approval of non-first-in-class drugs, will likely not result in lower drug list prices absent additional structural reforms.
Topics: Cost Savings; Cost-Benefit Analysis; Drug Costs; Economic Competition; Health Expenditures; Humans; Marketing of Health Services; Models, Economic; Prescription Drugs
PubMed: 31361747
DOI: 10.1371/journal.pmed.1002872 -
Addictive Behaviors Sep 2019We conducted a systematic review of the literature on cigar research on youth to identify potential future research agenda to generate evidence to inform cigar...
INTRODUCTION
We conducted a systematic review of the literature on cigar research on youth to identify potential future research agenda to generate evidence to inform cigar regulations to prevent cigar use among youth.
METHODS
We searched articles on Medline, EMBASE, and PsycINFO in April 2017 to identify articles relevant to cigars and adolescents. Two independent coders examined 48 articles to determine eligibility: (1) published between 2000-April 2017; (2) published in English; (3) conducted in the United States; (4) published in a peer-review journal; (5) examined cigars, cigarillos, or little cigars; (6) included youth (12-18 years old); and (7) included empirical data. Three independent coders reviewed the included articles (n = 48) to identify whether the studies addressed FDA's Research Priorities.
RESULTS
The studies addressed FDA's Research Priorities of "behavior" (n = 48), "communications" (n = 4), "marketing influences" (n = 1), and "impact analysis" (n = 1). Studies on "behavior" underscored the need for improvements in measurement, such as using brand names and distinguishing cigar products. The review revealed the need for restrictions on cigar flavors, development of media campaigns and interventions, increasing the cost (via taxation), and evaluating the impact of cigar policies.
CONCLUSIONS
The studies mostly focused on surveillance of behaviors and use patterns, which revealed cigar specific issues to address in policies to decrease cigar use among youth. The lack of studies addressing other FDA's research priorities highlighted the critical need for future studies that inform prevention of youth cigar use.
Topics: Adolescent; Adolescent Behavior; Cigar Smoking; Communication; Humans; Marketing; Public Policy; Research; Smoking Cessation; Smoking Prevention; Tobacco Products; United States; United States Food and Drug Administration
PubMed: 31125939
DOI: 10.1016/j.addbeh.2019.04.032 -
Journal of Public Health Management and... 2019Students may lose knowledge and skills achieved in the school year during the summer break, with losses greatest for students from low-income families. Community Guide...
Examining the Effectiveness of Year-Round School Calendars on Improving Educational Attainment Outcomes Within the Context of Advancement of Health Equity: A Community Guide Systematic Review.
Students may lose knowledge and skills achieved in the school year during the summer break, with losses greatest for students from low-income families. Community Guide systematic review methods were used to summarize evaluations (published 1965-2015) of the effectiveness of year-round school calendars (YRSCs) on academic achievement, a determinant of long-term health. In single-track YRSCs, all students participate in the same school calendar; summer breaks are replaced by short "intersessions" distributed evenly throughout the year. In multi-track YRSCs, cohorts of students follow separate calendar tracks, with breaks at different times throughout the year. An earlier systematic review reported modest gains with single-track calendars and no gains with multi-track calendars. Three studies reported positive and negative effects for single-track programs and potential harm with multi-track programs when low-income students were assigned poorly resourced tracks. Lack of clarity about the role of intersessions as simple school breaks or as additional schooling opportunities in YRSCs leaves the evidence on single-track programs insufficient. Evidence on multi-track YRSCs is also insufficient.
Topics: Child; Education; Educational Status; Health Equity; Humans; Schools
PubMed: 30325796
DOI: 10.1097/PHH.0000000000000860