Improving alignment in total knee arthroplasty: a cadaveric assessment of a surgical navigation tool with computed tomography imaging.

PURPOSE: To investigate the accuracy of an imageless, optical surgical navigation tool to assist with femoral and tibial bone cuts performed during TKA. PATIENTS AND METHODS: Six board-certified orthopedic surgeons participated in a laboratory cadaver investigation, performing femoral and tibial bone cuts with the assistance of a computer navigation tool. Femoral and tibial varus/valgus, tibial slope, femoral flexion, and both femoral and tibial rotation measurements from the device were compared with angular measurements calculated from computed tomography (CT) images of the knees. RESULTS: Measurements with the navigation tool were highly correlated with those obtained from CT scans in all three axes. For the distal femoral cut, the absolute mean difference in varus/valgus was 0.83° (SD 0.46°, r = 0.76), femoral flexion was 1.91° (SD 1.16°, r = 0.85), and femoral rotation was 1.29° (SD 1.01°, r = 0.88) relative to Whiteside's line and 0.97° (SD 0.56°, r = 0.81) relative to the posterior condylar axis. For the tibia, the absolute mean difference in varus/valgus was 1.08° (SD 0.64°, r = 0.85), posterior slope was 2.78° (SD 1.40°, r = 0.60), and rotation relative to the anteroposterior axis (posterior cruciate ligament to the medial third of the tibial tuberosity) was 2.98° (SD 2.54°, r = 0.79). CONCLUSION: Utilization of an imageless navigation tool may aid surgeons in accurately performing and monitoring femoral and tibial bone cuts, and implant rotation in TKA and thus, more accurately align TKA components.

Radiographic measurement of leg-length change in the nonoperative leg during total hip arthroplasty: a potential indicator of imaging error?

BACKGROUND: Anteroposterior (AP) pelvic radiographs are subject to errors that may cause measurement inaccuracy in total hip arthroplasty (THA). Such errors may be detected by measuring pre- to postoperative leg-length changes in the nonoperative leg, which experiences no physical changes during THA. METHODS: From AP pelvic radiographs, we measured pre- to postoperative leg-length changes (LLC) in the nonoperative legs of 67 patients who underwent primary THA using the trans-ischial line method. RESULTS: An LLC of 0 mm was observed in the nonoperative leg in only 14 cases (21%). A LLC ⩾ 2 mm was observed in 27% (18/67) of cases, including 13% (9/67) with LLC ⩾ 3 mm and 6% (4/67) with LLC ⩾ 4 mm. A post-hoc analysis used a validated method to measure change in pelvic tilt between pre- and postoperative images and found that changes in pelvic tilt ⩾ 4° in the anterior and posterior directions created apparent lengthening (2.0 ± 1.4 mm, p < 0.001 vs. 0-3° of tilt) and shortening (-2.1 ± 1.6 mm, p < 0.001 vs. 0-3° of tilt) of the nonoperative leg, respectively. CONCLUSIONS: The current study provides evidence of measurement errors in leg length using AP pelvic radiographs following THA. Changes in pelvic tilt may be in part responsible for these errors, with the direction of change in pelvic tilt influencing the apparent lengthening or shortening of the lower limb. Ultimately, these findings may influence the radiographic measurement and interpretation of leg-length changes following THA.

Efficacy of non-surgical treatments for androgenetic alopecia in men and women: a systematic review with network meta-analyses, and an assessment of evidence quality.

BACKGROUND AND OBJECTIVE: Various treatments exist for androgenetic alopecia (AGA); we determined the relative efficacies of non-surgical AGA monotherapies separately for men and women. METHODS: Randomized controlled trials (RCTs) were systematically searched in PubMed, EMBASE, Scopus and clinicaltrials.gov. Separate networks were used for men and women; for each network, a Bayesian network meta-analysis (NMA) of mean change in hair count from baseline (in units of hairs per square centimeter) was performed using a random effects model. RESULTS: The networks for male and female AGA included 30 and 10 RCTs, respectively. We identified the following treatments for male AGA in decreasing rank of efficacy: platelet-rich plasma (PRP), low-level laser therapy (LLLT), 0.5 mg dutasteride, 1 mg finasteride, 5% minoxidil, 2% minoxidil, and bimatoprost. For female AGA the following were identified in decreasing rank of efficacy: LLLT, 5% minoxidil, and 2% minoxidil. The evidence quality of the highest ranked therapies, for male and female AGA, was judged to be low. CONCLUSIONS: While newer treatments like LLLT may be more efficacious than more traditional therapies like 5% minoxidil, the efficacy of the more recent treatment modalities needs to be further validated by future RCTs.

Validation of a Novel Software Measurement Tool for Total Hip Arthroplasty.

Background Preoperative planning and postoperative evaluation of component position in total hip arthroplasty (THA) utilize specialized software that must be able to provide measurements that are both accurate and precise. A new software program for use in THA has recently been developed. We sought to evaluate the accuracy of this new software in comparison with two current, widely used software programs. Methodology Postoperative anteroposterior (AP) pelvic radiographs from 135 THA patients were retrospectively reviewed. Reference values for acetabular anteversion, inclination, and leg length were established using validated software programs (TraumaCad® as the primary reference value [PRV] and OsiriX LiteTM as the secondary reference value [SRV]). Measurements from the new software program (Intellijoint VIEWTM) were compared with reference values using Student's t-test and chi-square test. Results For anteversion, mean values for the PRV (27.34° ± 7.27°) and the new software (27.29° ± 7.21°) were not significantly different (p = 0.49). The new software differed from the PRV by a mean of 0.05° ± 0.93°. Similar results were noted for inclination, where the new software differed from the PRV and SRV by -0.13° ± 0.65° and 0.25° ± 1.26°, respectively (mean values: PRV: 43.62° ± 6.02°; SRV: 43.99° ± 6.27°; new software: 43.74° ± 6.17°; p = 0.87), and for leg length, where the new software differed from the PRV and SRV by 0.05 mm ± 0.46 mm and 0.22 mm ± 0.52 mm, respectively (mean values: PRV: 10.61 mm ± 11.60 mm; SRV: 10.77 mm ± 11.70 mm; new software: 10.56 mm - ± 11.61 mm; p = 0.98). Measurements were highly correlated across multiple reviewers (intraclass correlation coefficient ≥0.987). Conclusions The new software measurement tool is accurate and precise for assessing the acetabular component position and leg length measurements following THA in AP pelvic radiographs compared to currently used image measurement software.

Examining the non-spatial pretraining effect on a water maze spatial learning task in rats treated with multiple intracerebroventricular (ICV) infusions of propionic acid: Contributions to a rodent model of ASD.

Propionic acid (PPA) is produced by enteric gut bacteria and is a dietary short chain fatty acid. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioural changes, including adverse effects on cognition, similar to those seen in autism spectrum disorders (ASD). Previous research has shown that repeated ICV infusions of PPA result in impaired spatial learning in a Morris water maze (MWM) as evidenced by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than control rats. In the current study rats were first given non-spatial pretraining (NSP) in the water maze in order to familiarize the animals with the general requirements of the non-spatial aspects of the task before spatial training was begun. Then the effects of ICV infusions of PPA on acquisition of spatial learning were examined. PPA treated rats failed to show the positive effects of the non-spatial pretraining procedure, relative to controls, as evidenced by increased search latencies, longer distances travelled, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. Thus, PPA treatment blocked the effects of the pretraining procedure, likely by impairing sensorimotor components or memory of the pretraining.

Continuous terbinafine and pulse itraconazole for the treatment of non-dermatophyte mold toenail onychomycosis.

INTRODUCTION: Although dermatophytes are considered the predominant causative organisms in onychomycosis, non-dermatophyte mold (NDM) infections may be more prevalent than originally thought and may be more difficult to treat. There are limited data of oral antifungal efficacy in treating NDM onychomycosis. METHOD: A retrospective chart review (2009-2016) was conducted in patients receiving continuous oral terbinafine or pulse itraconazole for toenail onychomycosis due to NDMs. Mycology results and percent nail affected were recorded with patient characteristics including demographics and concurrent diseases. Complete, clinical, and mycological cure were tabulated. RESULTS: Data from 176 patients were collected. Mycological and complete cure rates for terbinafine (69.8% and 17%) and itraconazole (67.5% and 22%) were not significantly different from each other. Regardless of oral treatment, age (p = .013), baseline severity (p = .016), and presence of atherosclerosis (p = .040) or hyperlipidemia (p = .033) decreased the likelihood of mycological cure, while age decreased the likelihood of complete cure (p = .001). CONCLUSION: Continuous terbinafine and pulse itraconazole were similar in efficacy for curing NDM onychomycosis. Age was the most consistent prognostic factor affecting likelihood of cure, with factors that may influence drug reaching the site of infection also decreasing likelihood of mycological cure.

Propionic acid induced behavioural effects of relevance to autism spectrum disorder evaluated in the hole board test with rats.

Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by abnormal social interactions, impaired language, and stereotypic and repetitive behaviours. Among genetically susceptible subpopulations, gut and dietary influences may play a role in etiology. Propionic acid (PPA), produced by enteric gut bacteria, crosses both the gut-blood and the blood-brain barrier. Previous research has demonstrated that repeated intracerebroventricular (ICV) infusions of PPA in adult rats produce behavioural and neuropathological changes similar to those seen in ASD patients, including hyperactivity, stereotypy, and repetitive movements. The current study examined dose and time related changes of exploratory and repetitive behaviours with the use of the hole-board task. Adult male Long-Evans rats received ICV infusions twice a day, 4 h apart, of either buffered PPA (low dose 0.052 M or high dose 0.26 M, pH 7.5, 4 µL/infusion) or phosphate buffered saline (PBS, 0.1 M) for 7 consecutive days. Locomotor activity and hole-poke behaviour were recorded daily in an automated open field apparatus (Versamax), equipped with 16 open wells, for 30 min immediately after the second infusion. In a dose dependent manner PPA infused rats displayed significantly more locomotor activity, stereotypic behaviour and nose-pokes than PBS infused rats. Low-dose PPA animals showed locomotor activity levels similar to those of PBS animals at the start of the infusion schedule, but gradually increased to levels comparable to those of high-dose PPA animals by the end of the infusion schedule, demonstrating a dose and time dependent effect of the PPA treatments.

Monotherapy for Alopecia Areata: A Systematic Review and Network Meta-Analysis.

BACKGROUND: There are many treatments available for alopecia areata; however, none are approved by the US Food and Drug Administration. Thus, there is clinician benefit in efficacy comparison. METHODS: A network meta-analysis was used to create direct and indirect comparisons of alopecia areata studies in addition to an inconsistency analysis, risk of bias, and quality of evidence assessment. RESULTS: For mild disease, intralesional corticosteroids were ranked the most likely to produce a response at 78.9% according to SUCRA (surface under the cumulative ranking curve) followed by topical corticosteroids (67.9%), prostaglandin analogs (67.1%), diphenylcyclopropenone (DPCP, 63.4%), topical minoxidil (61.2%), and squaric acid dibutylester (SADBE, 35.0%). In contrast, for moderate to severe disease (>50% scalp hair loss), DPCP was the top-ranked treatment (87.9%), followed by laser (77.9%), topical minoxidil (55.5%), topical corticosteroids (50.1%), SADBE (49.7%), and topical tofacitinib (47.6%). There were insufficient eligible trials to include oral tofacitinib in the network. CONCLUSION: Statistically significant evidence is presented for the use of intralesional and topical corticosteroids for treatment of mild disease and DPCP, laser, SADBE, topical minoxidil and topical corticosteroids for moderate to severe disease. Further controlled trials are required to analyze the relative efficacy of oral tofacitinib.

Impaired Spatial Cognition in Adult Rats Treated with Multiple Intracerebroventricular (ICV) Infusions of the Enteric Bacterial Metabolite, Propionic Acid, and Return to Baseline After 1 Week of No Treatment: Contribution to a Rodent Model of ASD.

Propionic acid (PPA) is a dietary short chain fatty acid and an enteric bacterial metabolite. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioral changes similar to those seen in autism spectrum disorders (ASD), including perseveration. The effects of ICV infusions of PPA on spatial cognition were examined by giving rats infusions of either PPA (0.26 M, pH 7.4, 4 µl/infusion) or phosphate-buffered saline (PBS, 0.1 M) twice a day for 7 days. The rats were then tested in the Morris water maze (MWM) for acquisition of spatial learning. After a recovery period of 1 week of no treatment, the rats were then tested for reversal of spatial learning in the MWM. PPA-treated rats showed impaired spatial learning in the maze, relative to controls, as demonstrated by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. After a recovery period of 1 week of no treatment, these animals exhibited normal spatial reversal learning indicating that the behavioral cognitive deficits caused by PPA seem to be reversible.

Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder.

The role of the gut microbiome and its enteric metabolites, such as short-chain fatty acids (SCFAs), in the etiology of autism spectrum disorders (ASDs) has recently received increased attention. Of particular interest has been the SCFA, propionic acid (PPA). Several different rodent models have been developed using PPA treatment to examine behaviors of relevance to ASD. The effects of systemic (intraperitoneal, i.p.) administration of PPA on social behavior, anxiety-related behavior, and locomotor activity in juvenile male rats (age 35 days) were examined in this study. Rats received seven i.p. injections of buffered PPA (500 mg/kg) or phosphate-buffered saline. Behavior was video-recorded during social interaction in a large open field (first four injections) or assessed in an automated activity system (individual animals, last three injections). PPA treatment significantly reduced social interaction, increased anxiety-related behavior, and produced hypoactivity and increased abnormal motor movements. These findings suggest that PPA alters behaviors of relevance to ASD in juvenile rats. These results contribute to the behavioral validity of the rodent model of ASD with systemic PPA treatment.

Evidence for biofilms in onychomycosis.

Onychomycosis is a difficult to treat fungal infection of the nails. The chronic nature of onychomycosis contributes to high recurrence rates and the difficulty in treating both dermatophyte and non-dermatophyte infections. It has been hypothesized that the formation of biofilms, sessile, multicellular communities of fungi surrounded by a protective extracellular matrix, allow for fungi to evade current antifungal therapies and contribute to observed antifungal resistance. This review presents the experimental evidence that has accumulated in recent years implicating biofilms in the pathogenesis of onychomycosis. Dermatophytes, non-dermatophyte molds, and yeasts form biofilms in vitro and a model using ex vivo healthy nail fragments has demonstrated biofilm formation on nails for dermatophyte, Candida, and Fusarium species. Implications for disease management are discussed with further research required to incorporate biofilm formation into future drug/device evaluation and treatment protocols.

In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails.

BACKGROUND: Topical antifungal treatments for onychomycosis are applied to clean, unpolished nails for 48 weeks or longer. Patients often wish to mask their infection with nail polish yet there is no evidence to suggest antifungal efficacy in the presence of nail polish. OBJECTIVE: To determine if tavaborole retains the ability to penetrate the nail plate and inhibit fungal growth in the presence of nail polish. METHOD: Tavaborole was applied to human fingernails painted with 2 or 4 coats of nail polish, and unpainted nails in an ex vivo model. Nails were mounted on TurChub® chambers seeded with Trichophyton rubrum and allowed to incubate for 7 days. Antifungal activity was assessed by measuring zones of inhibition. RESULTS AND CONCLUSION: Tavaborole exhibited antifungal activity in all experimental groups. The zones of inhibition of T. rubrum for all experimental groups (2 or 4 coats of polish, unpolished) were greater than infected controls (polished and unpolished), ps < .001. Tavaborole penetrates polished nails and kills T. rubrum in this ex vivo model.

Topical antifungal treatment prevents recurrence of toenail onychomycosis following cure.

Recurrence rates are high for onychomycosis, with prophylactic topical antifungal use proposed to counter recurrence. Although this is a reasonable action for many clinicians, few studies have been conducted on the efficacy of topical prophylaxis. A retrospective chart review (2010-2015) was conducted in patients receiving oral terbinafine or itraconazole for toenail onychomycosis. Following complete cure, a topical antifungal (amorolfine, bifonazole, ciclopirox olamine, or terbinafine spray) was used weekly as prophylaxis. Recurrence was recorded along with patient characteristics including demographics and concomitant medical conditions. Data from 320 patients were collected. Recurrence was significantly lower in patients receiving topical antifungal prophylaxis than in no prophylactic treatment following oral terbinafine (p < .001), but not itraconazole (p = .185). Regardless of oral treatment, the use of topical antifungals as prophylaxis (p < .001) decreased, and the number of affected toenails (p = .048) and family history of fungal infections (p < .001) increased the likelihood that recurrence would occur. This study supports the use of topical antifungal medications as prophylactic treatment to help prevent recurrence of toenail onychomycosis and suggests that those with a family history of fungal infections should be closely monitored.

New Antifungal Agents and New Formulations Against Dermatophytes.

A variety of oral and topical antifungal agents are available for the treatment of superficial fungal infections caused by dermatophytes. This review builds on the antifungal therapy update published in this journal for the first special issue on Dermatophytosis (Gupta and Cooper 2008;166:353-67). Since 2008, there have not been additions to the oral antifungal armamentarium, with terbinafine, itraconazole, and fluconazole still in widespread use, albeit for generally more severe or recalcitrant infections. Griseofulvin is used in the treatment of tinea capitis. Oral ketoconazole has fallen out of favor in many jurisdictions due to risks of hepatotoxicity. Topical antifungals, applied once or twice daily, are the primary treatment for tinea pedis, tinea corporis/tinea cruris, and mild cases of tinea unguium. Newer topical antifungal agents introduced include the azoles, efinaconazole, luliconazole, and sertaconazole, and the oxaborole, tavaborole. Research is focused on developing formulations of existing topical antifungals that utilize novel delivery systems in order to enhance treatment efficacy and compliance.

Lasers for Onychomycosis.

Many studies that have been recently published investigate the efficacy of laser treatment for onychomycosis. These studies support the current US Food and Drug Administration (FDA) approval of lasers for the 'temporary increase in clear nail'. Clear nail growth is an important treatment goal for patients; however, many do not realise that laser treatment is not a cure for onychomycosis. The current article briefly reviews why lasers may be theoretically effective in treating onychomycosis and critically reviews published laser studies for onychomycosis in light of the standards employed in drug trials. Treatment regimens, efficacy endpoints, and the unit of analysis (nails vs patients) vary widely among published laser studies. Complete cure, mycological cure, and clinical improvement rates in laser studies are not reported or use such disparate criteria that comparison among studies is not possible. The US FDA has recently published guidelines for the use of medical devices in clinical trial design for onychomycosis. Future laser studies should adopt the FDA's guidelines to allow for more consistency within the field and focus on the efficacy of lasers as monotherapy for onychomycosis.

A Critical Assessment of the Evidence for Low-Level Laser Therapy in the Treatment of Hair Loss.

BACKGROUND: Low-level laser therapy (LLLT) is currently in use to stimulate hair growth and is quickly gaining in popularity due to the ease of use and absence of side effects. In 2015 alone, the number of LLLT devices with the Food and Drug Administration clearance has doubled. OBJECTIVE: To consolidate evidence and establish which data are still required for the widespread acceptance of LLLT for hair loss therapy. METHODS AND MATERIALS: A thorough search of the PubMed database was conducted to obtain studies investigating LLLT for androgenetic alopecia in men and women. RESULTS: Nine trials were identified for comb and helmet/cap devices, five of which were randomized controlled trials. Data comparison across LLLT trials and with traditional hair loss therapy (minoxidil, finasteride) was not straight forward because there was a lack of visual evidence, sample sizes were low, and there were large variations in study duration and efficacy measurements. CONCLUSION: There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences of LLLT use. Moving forward, protocols should be standardized across trials. Moreover, it is recommended that future trials include visual evidence and trial duration be expanded to 12 months.

Clinical trials of lasers for toenail onychomycosis: The implications of new regulatory guidance.

BACKGROUND: Despite the fact that lasers are presently indicated for the cosmetic outcome "temporary increase in clear nail", these devices are increasingly used to treat onychomycosis and particularly in patients who are unwilling or unable to take oral antifungal medication. The US Food and Drug Administration (FDA) recently issued draft guidance for medical device trials for onychomycosis. OBJECTIVE: This review evaluates the quality of laser trials for onychomycosis and compares the design guidelines for medical devices and antifungal drugs. METHOD: The PubMed database up to 29 May 2015 was searched for clinical studies of laser treatment for onychomycosis. RESULTS: The evidence demonstrating that lasers eradicate pathogenic fungi is limited and published laser trials suffer from limitations such as incomplete reporting of randomization and lack of stratified analyzes for fingernail/toenail data and infecting organisms. Differences in inclusion criteria and efficacy outcomes between drug and device guidelines may prevent the comparison of results from device and drug trials. CONCLUSION: We propose the standardization of device guidelines to match those of antifungal drug trials. Patients and physicians need to be aware of the capabilities and limitations of laser treatment for onychomycosis.

Improving Cure Rates in Onychomycosis.

BACKGROUND: Onychomycosis is a persistent fungal nail infection that is notoriously hard to treat. Approximately 20% to 25% of patients with onychomycosis do not respond to treatment, and 10% to 53% of patients relapse. As such, successful treatment is imperative for long-term disease management. OBJECTIVE: To identify ways to improve cure rates for onychomycosis. METHOD: The literature on onychomycosis treatment and recurrence was reviewed to summarize treatment approaches and suggest strategies to increase cure rates. RESULTS AND CONCLUSION: To improve treatment success in onychomycosis, we suggest the following measures be followed: (1) onychomycosis must be correctly diagnosed, (2) the treatment regimen should be tailored to the individual patient, (3) the efficacy of antifungals must be maximized, and (4) recurrence must be prevented.