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The Cochrane Database of Systematic... May 2017Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE.
OBJECTIVES
To assess the effects of drugs for discoid lupus erythematosus.
SEARCH METHODS
We updated our searches of the following databases to 22 September 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant trials. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of drugs to treat people with DLE in any population group and of either gender. Comparisons included any drug used for DLE against either another drug or against placebo cream. We excluded laser treatment, surgery, phototherapy, other forms of physical therapy, and photoprotection as we did not consider them drug treatments.
DATA COLLECTION AND ANALYSIS
At least two reviewers independently extracted data onto a data extraction sheet, resolving disagreements by discussion. We used standard methods to assess risk of bias, as expected by Cochrane.
MAIN RESULTS
Five trials involving 197 participants were included. Three new trials were included in this update. None of the five trials were of high quality.'Risk of bias' assessments identified potential sources of bias in each study. One study used an inappropriate randomisation method, and incomplete outcome data were a concern in another as 15 people did not complete the trial. We found most of the trials to be at low risk in terms of blinding, but three of the five did not describe allocation concealment.The included trials inadequately addressed the primary outcome measures of this review (percentage with complete resolution of skin lesions, percentage with clearing of erythema in at least 50% of lesions, and improvement in patient satisfaction/quality of life measures).One study of fluocinonide cream 0.05% (potent steroid) compared with hydrocortisone cream 1% (low-potency steroid) in 78 people reported complete resolution of skin lesions in 27% (10/37) of participants in the fluocinonide cream group and in 10% (4/41) in the hydrocortisone group, giving a 17% absolute benefit in favour of fluocinonide (risk ratio (RR) 2.77, 95% CI 0.95 to 8.08, 1 study, n = 78, low-quality evidence). The other primary outcome measures were not reported. Adverse events did not require discontinuation of the drug. Skin irritation occurred in three people using hydrocortisone, and one person developed acne. Burning occurred in two people using fluocinonide (moderate-quality evidence).A comparative trial of two oral agents, acitretin (50 mg daily) and hydroxychloroquine (400 mg daily), reported two of the outcomes of interest: complete resolution was seen in 13 of 28 participants (46%) on acitretin and 15 of 30 participants (50%) on hydoxychloroquine (RR 0.93, 95% CI 0.54 to 1.59, 1 study, n = 58, low-quality evidence). Clearing of erythema in at least 50% of lesions was reported in 10 of 24 participants (42%) on acitretin and 17 of 25 (68%) on hydroxychloroquine (RR 0.61, 95% CI 0.36 to 1.06, 1 study, n = 49, low-quality evidence). This comparison did not assess improvement in patient satisfaction/quality of life measures. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The main adverse effects were dry lips (93% of the acitretin group and 20% of the hydroxychloroquine group) and gastrointestinal disturbance (11% of the acitretin group and 17% of the hydroxychloroquine group). Four participants on acitretin withdrew due to gastrointestinal events or dry lips (moderate-quality evidence).One trial randomised 10 people with DLE to apply a calcineurin inhibitor, pimecrolimus 1% cream, or a potent steroid, betamethasone 17-valerate 0.1% cream, for eight weeks. The study reported none of the primary outcome measures, nor did it present data on adverse events.A trial of calcineurin inhibitors compared tacrolimus cream 0.1% with placebo (vehicle) over 12 weeks in 14 people, but reported none of our primary outcome measures. In the tacrolimus group, five participants complained of slight burning and itching, and for one participant, a herpes simplex infection was reactivated (moderate-quality evidence).Topical R-salbutamol 0.5% cream was compared with placebo (vehicle) over eight weeks in one trial of 37 people with DLE. There was a significant improvement in pain and itch in the salbutamol group at two, four, six, and eight weeks compared to placebo, but the trial did not record a formal measure of quality of life. None of the primary outcome measures were reported. Changes in erythema did not show benefit of salbutamol over placebo, but we could not obtain from the trial report the number of participants with clearing of erythema in at least 50% of lesions. There were 15 events in the placebo group (experienced by 12 participants) and 24 in the salbutamol group (experienced by nine participants). None of the adverse events were considered serious (moderate-quality evidence).
AUTHORS' CONCLUSIONS
Fluocinonide cream may be more effective than hydrocortisone in clearing DLE skin lesions. Hydroxychloroquine and acitretin appear to be of equal efficacy in terms of complete resolution, although adverse effects might be more frequent with acitretin, and clearing of erythema in at least 50% of lesions occurred less often in participants applying acitretin. Moderate-quality evidence found adverse events were minor on the whole. There is not enough reliable evidence about other drugs used to treat DLE. Overall, the quality of the trials and levels of uncertainty were such that there is a need for further trials of sufficient duration comparing, in particular, topical steroids with other agents.
Topics: Acitretin; Albuterol; Calcineurin Inhibitors; Dermatologic Agents; Fluocinonide; Humans; Hydrocortisone; Hydroxychloroquine; Lupus Erythematosus, Discoid; Randomized Controlled Trials as Topic; Tacrolimus; Treatment Outcome
PubMed: 28476075
DOI: 10.1002/14651858.CD002954.pub3 -
Drug and Alcohol Dependence May 2023Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk of motor vehicle collisions after methadone use have been conflicting. In the present study, we compiled the available evidence on the risk of motor vehicle collisions after methadone use.
METHODS
We completed a systematic review and meta-analysis of studies identified on six databases. Two reviewers independently screened the identified epidemiological studies, extracted data, and used the Newcastle-Ottawa Scale to assess the quality of the studies. Risk ratios were retrieved for analysis, conducted using random-effects model. Sensitivity analyses, subgroup analyses, and tests for publication bias were conducted.
RESULTS
Among 1446 identified relevant studies, a total of 7 epidemiological studies enrolling 33226142 participants met the inclusion criteria. Overall, study participants with methadone use had a higher risk of motor vehicle collisions than did those without methadone use (pooled relative risk 1.92, 95% CI 1.25-2.95; number needed to harm 11.3, 95% CI 5.3-41.6); the I statistic was 95.1%, indicating substantial heterogeneity. Subgroup analyses revealed that database type explained 95.36% of the between-study variance (p = 0.008). Egger's (p = 0.376) and Begg's (p = 0.293) tests revealed no evidence of publication bias. Sensitivity analyses indicated that the pooled results were robust.
CONCLUSION
The present review revealed that methadone use is significantly associated with a nearly doubled risk of motor vehicle collisions. Therefore, clinicians should exercise caution in implementing methadone maintenance therapy for drivers.
Topics: Humans; Methadone; Opioid-Related Disorders; Opiate Substitution Treatment; Accidents, Traffic; Motor Vehicles
PubMed: 36933540
DOI: 10.1016/j.drugalcdep.2023.109832 -
The Cochrane Database of Systematic... Feb 2016People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments.
OBJECTIVES
To assess the efficacy and safety of topical treatments for scalp psoriasis.
SEARCH METHODS
We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis.
DATA COLLECTION AND ANALYSIS
Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high.
MAIN RESULTS
We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments.
AUTHORS' CONCLUSIONS
The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).
Topics: Administration, Topical; Chronic Disease; Dermatologic Agents; Humans; Psoriasis; Randomized Controlled Trials as Topic; Scalp Dermatoses; Steroids; Vitamin D
PubMed: 26915340
DOI: 10.1002/14651858.CD009687.pub2 -
The Cochrane Database of Systematic... Feb 2017Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian... (Review)
Review
BACKGROUND
Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation. Although both topical and systemic treatments are used to treat people with BKC, this Cochrane review focuses on topical treatments.
OBJECTIVES
To assess and compare data on the efficacy and safety of topical treatments (including antibiotics, steroids, immunosuppressants and lubricants), alone or in combination, for BKC in children from birth to 16 years.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE ( January 1946 to 11 July 2016), Embase (January 1980 to 11 July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We searched the reference lists of identified reports and the Science Citation Index to identify any additional reports of studies that met the inclusion criteria.
SELECTION CRITERIA
We searched for randomised controlled trials that involved topical treatments in children up to 16 years of age with a clinical diagnosis of BKC. We planned to include studies that evaluated a single topical medication versus placebo, a combination of treatments versus placebo, and those that compared two or multiple active treatments. We planned to include studies in which participants received additional treatments, such as oral antibiotics, oral anti-inflammatories, warm lid compresses and lid margin cleaning.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the literature search (titles and abstracts) to identify studies that met the inclusion criteria of the review and applied standards as expected for Cochrane reviews. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included one study from the USA that met the inclusion criteria. In the study, 137 children aged zero to six years old with blepharoconjunctivitis were randomised to treatment in one of four trial arms (loteprednol etabonate/tobramycin combination, loteprednol etabonate alone, tobramycin alone or placebo) for 15 days, with assessments on days 1, 3, 7 and 15. We judged the study to be at high risk of attrition bias and bias due to selective outcome reporting. The study did not report the number of children with improvement in symptoms nor with total or partial success as measured by changes in clinical symptoms.All children showed a reduction in blepharoconjunctivitis grade score, but there was no evidence of important differences between groups. Visual acuity was not fully reported but the authors stated that there was no change in visual acuity in any of the treatment groups. The study reported ocular and non ocular adverse events but was underpowered to detect differences between the groups. Ocular adverse events were as follows: loteprednol/tobramycin 1/34 (eye pain); loteprednol 4/35 (eye pain, conjunctivitis, eye discharge, eye inflammation); tobramycin 0/34; placebo (vehicle) 0/34. The evidence was limited for all these outcomes and we judged it to be very low certainty.There was no information on clinical signs (aside from grade score), disease progression or quality of life.
AUTHORS' CONCLUSIONS
There is no high-quality evidence of the safety and efficacy of topical treatments for BKC, which resulted in uncertainty about the indications and effectiveness of topical treatment. Clinical trials are required to test efficacy and safety of current and any future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.
Topics: Administration, Topical; Anti-Allergic Agents; Anti-Bacterial Agents; Blepharitis; Child; Child, Preschool; Conjunctiva; Eyelids; Humans; Infant; Infant, Newborn; Keratoconjunctivitis; Loteprednol Etabonate; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 28170093
DOI: 10.1002/14651858.CD011965.pub2 -
BMC Pediatrics Jun 2016Many clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical... (Comparative Study)
Comparative Study Review
BACKGROUND
Many clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical corticosteroids (TCS) have been widely used for >5 decades. Long-term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects. Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, available for 1-2 decades, are not associated with atrophy or increased percutaneous absorption after prolonged use and have much lower potential for systemic effects. However, since 2006 TCIs have carried a controversial Boxed Warning based on a theoretical risk of malignancy (eg, skin and lymphoma) that has limited TCI use for standard-of-care maintenance therapy.
METHODS
A comparative systematic search of PubMed was done for long-term (≥12 week) clinical trials of TCS or TCI treatment in patients <12 years with AD. Citations were reviewed for inclusion based on MeSH terms, abstracts, and relevant article text. Studies were excluded if they did not encompass subjects <12 years, or were <12 weeks' duration, retrospective, meta-analyses, or limited to anecdotal case reports.
RESULTS
Of 27 trials meeting criteria, 21 included 5825 pediatric patients treated with TCIs, and 6 included 1999 patients treated with TCS. TCS studies were limited to low- to mid-potency products, and all but one study lacked a vehicle control. Eight TCI studies were vehicle-controlled, and safety data were well reported, with ≤5 % of patients reporting discontinuation due to adverse effects (DAEs). Cutaneous and systemic adverse events (AEs) were similar in TCI and vehicle groups, with no reports of lymphoma. Safety data in TCS trials were less well reported. DAE incidence was addressed in just 2 trials, and systemic and cutaneous AEs were mostly unreported.
CONCLUSIONS
Data supporting long-term use of TCIs are robust, documenting safety and efficacy, while data supporting long-term TCS use are limited to low- to mid-potency products. Our review identifies a lack of information on the safety of commonly prescribed, long-term monotherapy with mid- to high-potency TCS in pediatric AD, and supports standard-of-care maintenance therapy with TCIs and intermittent use of low- to mid-potency TCS for flares.
Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Calcineurin Inhibitors; Child; Dermatitis, Atopic; Dermatologic Agents; Humans; Treatment Outcome
PubMed: 27267134
DOI: 10.1186/s12887-016-0607-9 -
Acta Dermato-venereologica Jan 2016This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for... (Review)
Review
This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.
Topics: Administration, Cutaneous; Aminoquinolines; Dermatologic Agents; Diterpenes; Drug Combinations; Facial Dermatoses; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Randomized Controlled Trials as Topic; Salicylic Acid; Scalp Dermatoses; Skin; Treatment Outcome
PubMed: 26068001
DOI: 10.2340/00015555-2167 -
Frontiers in Pharmacology 2016In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system.... (Review)
Review
In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of -values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
PubMed: 28119613
DOI: 10.3389/fphar.2016.00538 -
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 -
Medication use and the risk of motor vehicle collisions among licensed drivers: A systematic review.Accident; Analysis and Prevention Nov 2016Driving under the influence of prescription and over-the-counter medication is a growing public health concern. A systematic review of the literature was performed to... (Review)
Review
OBJECTIVES
Driving under the influence of prescription and over-the-counter medication is a growing public health concern. A systematic review of the literature was performed to investigate which specific medications were associated with increased risk of motor vehicle collision (MVC).
METHODS
The a priori inclusion criteria were: (1) studies published from English-language sources on or after January 1, 1960, (2) licensed drivers 15 years of age and older, (3) peer-reviewed publications, master's theses, doctoral dissertations, and conference papers, (4) studies limited to randomized control trials, cohort studies, case-control studies, or case-control type studies (5) outcome measure reported for at least one specific medication, (6) outcome measure reported as the odds or risk of a motor vehicle collision. Fourteen databases were examined along with hand-searching. Independent, dual selection of studies and data abstraction was performed.
RESULTS
Fifty-three medications were investigated by 27 studies included in the review. Fifteen (28.3%) were associated with an increased risk of MVC. These included Buprenorphine, Codeine, Dihydrocodeine, Methadone, Tramadol, Levocitirizine, Diazepam, Flunitrazepam, Flurazepam, Lorazepam, Temazepam, Triazolam, Carisoprodol, Zolpidem, and Zopiclone.
CONCLUSIONS
Several medications were associated with an increased risk of MVC and decreased driving ability. The associations between specific medication use and the increased risk of MVC and/or affected driving ability are complex. Future research opportunities are plentiful and worthy of such investigation.
Topics: Accidents, Traffic; Adult; Analgesics, Opioid; Antidepressive Agents; Automobile Driving; Cohort Studies; Dose-Response Relationship, Drug; Driving Under the Influence; Humans; Male; Middle Aged; Motor Vehicles; Risk Factors; Young Adult
PubMed: 27569655
DOI: 10.1016/j.aap.2016.08.001 -
Addiction Biology Jan 2024Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers... (Review)
Review
Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers are frequently employed to detect Δ9-tetrahydrocannabinol (THC) consumption among drivers during roadside tests, despite not necessarily indicating impairment. Characterising THC-specific alterations to oculomotor behaviour may offer a more sensitive measure for indexing drug-related impairment, necessitating discrimination between acute THC effects, chronic use and potential tolerance effects. The present review aims to synthesise current evidence on the acute and chronic effects of THC on driving-relevant oculomotor behaviour. The review was prospectively registered (10.17605/OSF.IO/A4H9W), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines informed reporting standards. Overall, 20 included articles comprising 12 experimental acute dosing trials, 5 cross-sectional chronic use studies and 3 roadside epidemiological studies examined the effects of cannabis/THC on oculomotor parameters including saccadic activity gaze behaviour, nystagmus, smooth pursuit and eyelid/blink characteristics. Acute THC consumption selectively impacts oculomotor control, notably increasing saccadic latency and inaccuracy and impairing inhibitory control. Chronic cannabis users, especially those with early age of use onset, display enduring oculomotor deficits that affect visual scanning efficiency. The presence of eyelid tremors appears to be a reliable indicator of cannabis consumption while remaining distinct from direct impairment associated with visual attention and motor control. Cannabis selectively influences oculomotor activity relevant to driving, highlighting the role of cannabinoid systems in these processes. Defining cannabis/THC-specific changes in oculomotor control may enhance the precision of roadside impairment assessments and vehicle safety systems to detect drug-related impairment and assess driving fitness.
Topics: Cannabis; Dronabinol; Cross-Sectional Studies; Cannabinoids; Cannabinoid Receptor Agonists
PubMed: 38221807
DOI: 10.1111/adb.13359