Topical and device-based treatments for fungal infections of the toenails.

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.

Revising Substantial Leg Length Discrepancy in Total Hip Arthroplasty Using Computer-assisted Navigated Systems: A Case Series of Three Patients.

One of the primary challenges of total hip arthroplasty (THA) is equalizing the limb lengths to re-establishing normal hip biomechanics. Post-operative leg length discrepancies (LLD) lead to patient dissatisfaction and are a main source of orthopedic malpractice cases. The aim of this case series was to document three cases of substantial LLD that were corrected during THA with the assistance of an imageless computer navigation system. Medical records were reviewed for history and radiographs were consulted. All patients in this series presented with complaints related to hip fractures and reported a significant lengthening of leg length following THA. No surgical complications of adverse events were reported. In these cases, imageless navigation provided intraoperative measurements of leg length which allowed for enhanced accuracy of component placement and improved outcomes following surgery.

Efficacy of Off-Label Topical Treatments for the Management of Androgenetic Alopecia: A Review.

Androgenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. A literature search was conducted to obtain randomized, controlled and blinded studies that investigated off-label, topical, monotherapies in male patients. Hair density, hair diameter and hair growth were used to evaluate treatment success. Fourteen off-label topical therapies were investigated among the 16 studies that met inclusion criteria. Nine off-label therapies were reported to produce a significantly greater improvement in hair restoration parameters (e.g. mean change from hair count and hair diameter) as compared to placebo (p < 0.05 for all treatments). In two studies, procyanidin oligomers exhibited greater efficacy over vehicle with response to mean change in hair density (hairs/cm2) (ps < 0.0001 at Week 24). In conclusion, prostaglandin analogs and polyphenols, such as latanoprost and procyanidin oligomers, can improve hair restoration parameters in male AGA patients, possibly through targeting mechanisms proposed in the etiology of AGA. The current evidence suggests short-term (24 weeks) use may provide benefit for hair loss patients; however, long-term efficacy and safety data are required.

Periacetabular osteotomy using an imageless computer-assisted navigation system: a new surgical technique.

Periacetabular osteotomy (PAO) is an effective surgical treatment for hip dysplasia. The goal of PAO is to reorient the acetabulum to improve joint stability, lessen contact stresses and slow the development of hip arthrosis. During PAO, the acetabulum is repositioned to adequately cover the femoral head. PAO preserves the weight-bearing posterior column of the pelvis, maintains the acetabular blood supply and retains the hip abductor musculature. The surgical technique needed to perform PAO is technically demanding, with correct repositioning of the acetabulum the most important-and challenging-aspect of the procedure. Imageless navigation has proven useful in other technically challenging surgeries, although its use in PAO has not yet been investigated. We have modified the standard technique for PAO to include the use of an imageless navigation system to confirm acetabular fragment position following osteotomy. Here, we describe the surgical technique and discuss the potential of this modified technique to improve patient-related outcomes.

Global perspectives for the management of onychomycosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophyte molds, and yeasts. This difficult-to-treat chronic infection has a tendency to relapse despite treatment. This paper aims to offer a global perspective on onychomycosis management from expert physicians from around the world. Overall, the majority of experts surveyed used systemic, topical, and combination treatments approved in their countries and monitored patients based on the product insert or government recommendations. Although the basics of treating onychomycosis were similar between countries, slight differences in onychomycosis management between countries were found. These differences were mainly due to different approaches to adjunctive therapy, rating the severity of disease and use of prophylaxis treatment. A global perspective on the treatment of onychomycosis provides a framework of success for the committed clinician with appreciation of how onychomycosis is managed worldwide.

The Impact of Onychomycosis on Quality of Life: A Systematic Review of the Available Literature.

PURPOSE: Onychomycosis is a nail disorder that is increasing in prevalence worldwide. The psychological and social limitations caused by onychomycosis can potentially undermine the work and social lives of those experiencing these negative effects. This review aimed to evaluate the randomized controlled trials (RCTs) available in the current literature on the impact onychomycosis has on quality of life (QoL). METHODS: A systematic review was performed using the databases PubMed, PsycINFO, Scopus, ClinicalTrials.gov, and Cochrane Library on July 18, 2017. Only RCTs with clinical effects described in English were included for review. RESULTS: Ten RCTs reported QoL outcomes for patients suffering from onychomycosis. Treatment satisfaction was statistically significant from baseline to end of treatment in 100.0% (4/4) measures which reported on satisfaction with treatment; mental health was also significant in 100.0% (3/3), symptoms index rating in 100.0% (2/2), symptom frequency in 75.0% (3/4), overall problems in 75.0% (3/4), functional activities in 75.0% (6/8), appearance problems in 66.7% (2/3), symptom distress in 57.1% (4/7), and stigma in 40.0% (2/5). The OnyCOE-tTM and the NailQoL were the most used common outcome measures to describe QoL. CONCLUSION: The study sanctions that onychomycosis physically and psychologically distresses patients' lives. Further research should include validated outcome measures to more effectively treat onychomycosis.

Update on current approaches to diagnosis and treatment of onychomycosis.

INTRODUCTION: Onychomycosis is a chronic fungal infection of the nail bed, matrix or plate. It accounts for roughly 50% of all nail disease. As the prevalence of onychomycosis is increasing, a critical review of diagnostic techniques and treatment options is required. Areas covered: This review discusses the current diagnostic techniques associated with diagnosing onychomycosis, such as microscopy, culture, periodic acid Schiff stain (PAS) and polymerase chain reaction (PCR). Oral and topical therapies are also discussed, as well as, the utility of device-based treatments and combination therapy. Expert commentary: Culture for the diagnosis of onychomycosis is the gold standard; however, PCR is more sensitive and should be considered. In general, topical treatments are recommended for mild to moderate disease and oral treatments should be considered for moderate to severe disease. Combination therapy and device-based treatments may enhance cure rates, further study is required.

Onychomycosis in children: Safety and efficacy of antifungal agents.

Onychomycosis is an uncommon condition in childhood, but prevalence in children is increasing worldwide.The objective was to review the efficacy and safety of systemic and topical antifungal agents to treat onychomycosis in children. Databases (Pubmed, OVID, Scopus, clinicaltrials.gov, Cochrane Library) were searched. Seven studies were selected for inclusion. Only one was a randomized controlled trial. In total, 208 children were administered antifungal agents for the treatment of onychomycosis. Four reports of mild adverse events were documented (1.9% of treated children), one of which discontinued treatment (0.5%). Limitations of this review are the lack of randomized controlled trials available in pediatric onychomycosis. These findings suggest that antifungal therapies used to treat onychomycosis in children are associated with a low incidence of adverse events. Current dosing regimens for antifungal drugs are effective and appear safe to use in children, notwithstanding that the Food and Drug Administration has not approved any of these agents for the treatment of onychomycosis in children. To our knowledge, this review is the most up-to-date, comprehensive summary of pediatric onychomycosis treatment.

Methodological Quality of Motor Intervention Randomized Controlled Trials in Stroke Rehabilitation.

PURPOSE: The objective of the study was to evaluate the methodological quality of motor intervention randomized controlled trials (RCTs) published in the stroke rehabilitation literature and to examine trends in quality over time. METHODS: A systematic literature search was conducted for all English articles (published up to December 2013) examining rehabilitation for motor recovery poststroke. All RCTs with a human sample, of which at least 50% had a stroke, were included in the analysis. A Physiotherapy Evidence Database (PEDro) score was assigned to assess methodological quality. A one-way analysis of variance was conducted to examine adherence to quality items overall and over time, with post hoc t-tests performed where appropriate. RESULTS: Six hundred seventy-six RCTs met inclusion criteria, of which 32.0% had excellent, 42.0% good, 23.1% fair, and 3.0% poor methodological qualities. The overall mean PEDro score was 6.6 ± 1.6; with scores improving significantly between 1979-1983 and 2009-2013 (5.0 ± 1.4 versus 7.0 ± 1.5; P = .0003); however, no significant improvements in individual items were found (P > .05). CONCLUSIONS: This study showed improvements in the total methodological quality of motor intervention RCTs in stroke rehabilitation over time. However, no relationship was found between individual quality items and improvement over time.

Examining the effectiveness of intrathecal baclofen on spasticity in individuals with chronic spinal cord injury: a systematic review.

OBJECTIVE: To review the available evidence on the effectiveness of intrathecal baclofen in the treatment of spasticity in individuals with spinal cord injuries (SCIs) at least 6 months post-injury or diagnosis. DATA SOURCES: A literature search of multiple databases (Pub Med, CINAHL, EMBASE) was conducted to identify articles published in the English language. STUDY SELECTION: Studies were included for review if: (1) more than 50% of the sample size had suffered a traumatic or non-traumatic SCI; (2) there were more than three subjects; (3) subjects received continuous intrathecal baclofen via an implantable pump aimed at improving spasticity; and (4) all subjects were ≥6 months post-SCI, at the time of the intervention. DATA EXTRACTION: Data extracted from the studies included patient and treatment characteristics, study design, method of assessment, and outcomes of the intervention. DATA SYNTHESIS: Methodological quality was assessed using the PEDro for randomized-controlled trials (RCTs) and the Downs and Black (D&B) tool for non-RCTs. A level of evidence was assigned to each intervention using a modified Sackett scale. CONCLUSION: The literature search resulted in 677 articles. No RCTs and eight non-RCTs (D&B scores 13-24) met criteria for inclusion, providing a pooled sample size of 162 individuals. There was substantial level 4 evidence that intrathecal baclofen is effective in reducing spasticity. Mean Ashworth scores reduced from 3.1-4.5 at baseline to 1.0-2.0 (P < 0.005) at follow-up (range 2-41 months). Average dosing increased from 57-187 µg/day at baseline to 218.7-535.9 µg/day at follow-up. Several complications from the use of intrathecal baclofen or pump and catheter malfunction were reported.

A review of educational programs to reduce UTIs among individuals with SCI.

PURPOSE: To evaluate the effectiveness of educational programs in reducing urinary tract infections (UTIs) in individuals with spinal cord injuries (SCI). METHODS: A search of all relevant literature published up to and including July 2012 was conducted using multiple databases. Methodological quality was rated using the PEDro tool for randomized control trials (RCTs) and the Downs and Black tool for non-RCTs; levels of evidence were assigned using a modified Sackett scale. FINDINGS: Four articles were selected for review. As a result of an education program, a level 2 prospective control trial reported a reduction in number of UTIs (p = .02), but a level 2 RCT did not. A pre-post study found a reduction in number of UTIs while a case-control study did not; however, these studies did not compute statistics. CONCLUSIONS: There is limited positive evidence that education programs reduce the incidence of UTIs. CLINICAL RELEVANCE: Optimal urinary health of individuals with SCI may be optimized via education programs that provide information and enhance skills.

Cardiovascular conditioning for comfortable gait speed and total distance walked during the chronic stage of stroke: a meta-analysis.

OBJECTIVE: To examine the effectiveness of cardiovascular conditioning on comfortable gait speed and total distance walked when initiated in the chronic stage of stroke through a meta-analysis. METHODS: MEDLINE, CINAHL, EMBASE, and Scopus databases were searched from 1980 to June 2012. A study was selected if (1) it was a randomized controlled trial; (2) individuals in the study were entered into the study at or over 6 months post stroke; (3) cardiorespiratory training was initiated during the chronic stage of stroke; and (4) study participants were ≥18 years of age. A standardized mean difference (SMD ± SE and 95% confidence interval [CI]) was calculated for comfortable gait speed and/or 6-minute walk test (6MWT). results from all studies were then pooled using a random effects model. Treatment effect sizes were interpreted as small, ≯0.2; moderate, ≯0.5; or large, ≯0.8. Methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro) tool. RESULTS: Seven studies met inclusion criteria. The analysis demonstrated a moderate and significant effect on 6MWT post treatment (SMD = 0.581 ± 0.277; 95% CI, -0.037 to 1.125; P = .036) with an improvement of 111.4 m to a pooled average of 357.7 m. No significant improvement in comfortable gait speed was noted post treatment (SMD = 0.159 ± 0.124; 95% CI, -0.085 to 0.402; P = .202) or at follow-up (SMD = 0.248 ± 0.256; 95% CI, -0.253 to 0.750; P = .332). CONCLUSION: Cardiovascular conditioning resulted in clinically relevant gains in walking distance of over 100 m post treatment on the 6MWT when initiated during the chronic stage of stroke. These results demonstrate that individuals in the chronic stage of stroke can still benefit from interventions to improve gait and mobility. This has important implications for outpatient and community-based programs.

Resistance training for gait speed and total distance walked during the chronic stage of stroke: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis examining the effectiveness of resistance training on comfortable gait speed and total distance walked when initiated in the chronic stage of stroke. METHODS: MEDLINE, CINAHL, EMBASE, and Scopus databases were searched from 1980 to June 2012. Studies were selected if they met the following criteria: (1) they were randomized controlled trials; (2) individuals in the studies were entered into the studies at or over 6 months post stroke; (3) resistance training was initiated during the chronic stage of stroke; and (4) study participants were ≥18 years of age. A standardized mean difference (SMD ± SE and 95% confidence interval [CI]) was calculated for at least 1 of the following outcomes in each study: comfortable gait speed and/or 6-minute walk test (6MWT). Treatment effect sizes were interpreted as follows: small, ≯0.2; moderate, ≯0.5; or large, ≯0.8. Study quality was assessed using the Physiotherapy Evidence Database (PEDro) tool. RESULTS: Ten randomized controlled trials met inclusion criteria. Significant improvement was seen for gait speed with a small effect size (0.295 ± 0.118; 95% CI, 0.063-0.526; P < .013) and a pooled post mean speed of 0.79 m/s, and for the 6MWT (0.247 ± 0.111; 95% CI, 0.030-0.465; P = .026) with a pooled post mean total distance walked of 271.9 m. CONCLUSION: This meta-analysis demonstrated that providing lower limb resistance training to community-dwelling individuals who are 6 months post stroke has the capacity to improve comfortable gait speed and total distance walked.

Systematic review of the effectiveness of pharmacological interventions in the treatment of spasticity of the hemiparetic lower extremity more than six months post stroke.

BACKGROUND: The long-term management of lower limb spasticity after stroke is an important aspect of an individual's physical recovery and quality of life. OBJECTIVE: To examine the effectiveness of pharmacological interventions in reducing spasticity of the lower limb in chronic stroke survivors. METHODS: PubMed, CINAHL, and EMBASE were searched for studies in which (1) ≥50% of the sample size had sustained a stroke; (2) the research design was a randomized controlled trial (RCT); (3) the mean time since stroke was ≥6 months for both the treatment and control groups, at the time treatment was initiated; (4) the treatment group received a pharmacological intervention aimed at treating lower limb spasticity; and (5) spasticity was assessed pre and post treatment. Methodological quality of each study was assessed using the PEDro tool. RESULTS: Nine RCTs (PEDro scores, 4-9) met inclusion criteria and included a pooled sample size of 605 individuals with a mean age of 54.8 years (range, 14-86). Four RCTs provided evidence that botulinum toxin type A was effective in reducing spasticity compared to persons receiving placebo or a phenol neurolytic. One study provided evidence that both alcohol and phenol neurolytics were effective in reducing spasticity. Finally, 4 studies provided evidence that oral and intrathecal medications were effective in reducing lower limb spasticity compared to placebo. CONCLUSIONS: Pharmacological treatment initiated 6 months post stroke reduced lower limb spasticity. Relevant areas of exploration for future research could include the period of effectiveness, long-term complications, and a cost-benefit analysis of such treatments.