Summary
Background
Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail‐related disease.
...Objectives
This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta‐analysis (NMA).
Methods
Quality of evidence was assessed using Cochrane‐compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Efficacy and safety outcomes were compared using a random‐effects NMA to estimate pooled odds ratios (ORs) of direct and indirect comparisons among oral and topical treatments (PROSPERO 2015: CRD42018086912). There were not enough eligible combination and device‐based therapy trials to include in the NMA.
Results
Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients). There were no significant inconsistencies between the direct and indirect evidence. Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure. The ORs of adverse events occurring with oral or topical treatments were not significantly different from each other. For mycological cure, evidence was of moderate or high quality while evidence ranged from very low to high quality for adverse events.
Conclusions
Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure.
What's already known about this topic?
Topical treatments traditionally have lower success rates than oral treatments.
Oral treatments have the advantage of shorter treatment durations, but also present challenges in cases of drug–drug interactions or immunosuppression.
A network meta‐analysis (NMA) gathers data from indirect evidence to gain confidence about all treatment comparisons and allows for estimation of comparative effects that have not been investigated in head‐to‐head randomized clinical trials (RCTs).
What does this study add?
This NMA of efficacy and safety includes all RCTs of oral, topical, combination and device‐based treatments for toenail onychomycosis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement for NMA.
The odds of achieving mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg were significantly greater than topical treatments.
Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure.
Linked Comment: Morris‐Jones. Br J Dermatol 2020; 182:263.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Onychomycosis is a fungal infection of the nail and is the most common nail affliction in the general population. Certain patient populations are at greater risk of infection and the prevalence of ...onychomycosis reported in the literature has yet to be summarized across these at‐risk groups. We performed a systematic review of the literature and calculated pooled prevalence estimates of onychomycosis in at‐risk patient populations. The prevalence of dermatophyte toenail onychomycosis was as follows: general population 3.22% (3.07, 3.38), children 0.14% (0.11, 0.18), the elderly 10.28% (8.63, 12.18), diabetic patients 8.75% (7.48, 10.21), psoriatic patients 10.22% (8.61, 12.09), HIV positive patients 10.40% (8.02, 13.38), dialysis patients 11.93% (7.11, 19.35) and renal transplant patients 5.17% (1.77, 14.14). Dialysis patients had the highest prevalence of onychomycosis caused by dermatophytes, elderly individuals had the highest prevalence of onychomycosis caused by yeasts (6.07%; 95% CI = 3.58, 10.11) and psoriatic patients had the highest prevalence of onychomycosis caused by non‐dermatophyte moulds (2.49%; 95% CI = 1.74, 3.55). An increased prevalence of onychomycosis in certain patient populations may be attributed to impaired immunity, reduced peripheral circulation and alterations to the nail plate which render these patients more susceptible to infection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Onychomycosis is difficult to treat and a concern for many patients. Prevalence estimates of onychomycosis in North American clinic samples have been higher than what has been reported for ...general populations.
Objective
A large, multicentre study was conducted to estimate the prevalence of toenail onychomycosis in the Canadian population.
Methods
Patients were recruited from the offices of three dermatologists and one family physician in Ontario, Canada. Nail samples for mycological testing were obtained from normal and abnormal‐looking nails. This sample of 32 193 patients includes our previous published study of 15 000 patients.
Results
Abnormal nails were observed in 4350 patients. Of these, the prevalence of culture‐confirmed toenail onychomycosis was estimated to be 6.7% (95% CI, 6.41–6.96%). Following sex and age adjustments for the general population, the estimated prevalence of toenail onychomycosis in Canada was 6.4% (95% CI, 6.12%–6.65%). The distribution of fungal organisms in culture‐confirmed onychomycosis was 71.9% dermatophytes, 20.4% non‐dermatophyte moulds and 7.6% yeasts. Toenail onychomycosis was four times more prevalent in those over the age of 60 years than below the age of 60 years.
Conclusion
The present data highlights that onychomycosis may be a growing medical concern among ageing patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
The occurrence of sexual dysfunction side‐effects associated with finasteride use in men with androgenetic alopecia (AGA) is thought to be less prevalent than is publicized. There is a ...need to investigate sexual dysfunction among finasteride users with population‐based controls.
Objective
To evaluate the presence of sexual dysfunction in men using finasteride or not using finasteride.
Method
Adult men visiting a dermatologist's office for any reason were asked to complete a survey including a modified version of the Arizona Sexual Experience Scale (ASEX) to assess the presence of sexual dysfunction with and without finasteride use.
Results
Data from 762 men aged 18–82 were collected: 663 finasteride users and 99 non‐finasteride users. There were no significant differences between finasteride users and non‐user controls in reporting sexual dysfunction using the ASEX. Regression analysis indicated that self‐reporting libido loss and reduced sexual performance, not finasteride use, predict a higher ASEX score.
Conclusion
The use of finasteride does not result in sexual dysfunction in men with AGA. These data are consistent with other large survey‐based controlled studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant ...proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear.
Objective
To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple‐treatment meta‐analysis.
Methods
This systematic review and network meta‐analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta‐analysis.
Results
The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks – but not 12 weeks – was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9–12 months. Rank probabilities demonstrated that 24‐week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events.
Conclusion
More knowledge about the fungal life cycle and drugs’ pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti‐interleukin‐23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are ...complete.
Objectives
We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2.
Methods
reSURFACE 1 and reSURFACE 2 were double‐blind, randomized, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter reSURFACE 2 included an etanercept (ETN) arm. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated.
Results
Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient‐years of TIL 100 and TIL 200, respectively.
Conclusions
TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.
What’s already known about this topic?
Tildrakizumab (TIL) is approved for treatment of moderate‐to‐severe psoriasis, and 3‐year data have been previously published.
Long‐term efficacy and safety data of biological therapies is crucial to inform clinical practice.
What does this study add?
TIL is the first anti‐interleukin‐23p19 treatment for which 5‐year efficacy and safety data are reported from two phase III studies, reSURFACE 1 and reSURFACE 2.
These data provide evidence of sustained efficacy in TIL responders and in patients switched from etanercept to TIL at week 28, and a favourable long‐term safety profile with total TIL exposure of over 5400 patient‐years.
Linked Comment: C.G. Purvis et al. Br J Dermatol 2021; 185:242–243.
Plain language summary available online
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Widespread public engagement with antibiotic stewardship is essential to stem the rising incidence of antibiotic-resistant infections; however, campaigns that focus on increasing knowledge have not ...been effective. Beliefs about who is responsible for causing and solving antibiotic resistance (AR) likely influences engagement in antibiotic stewardship behaviors. This study assesses the U.S. public's AR causal and solution responsibility attributions and the capacity for changing these attributions to inform future antibiotic stewardship campaigns. U.S. participants (N= 1,014) diverse across race, education, and geographic region were surveyed on their beliefs about responsibility for AR for themselves, the general public, healthcare providers, scientists, and drug companies. Substantial percentages of participants held causal and solution beliefs about antibiotic resistance that likely inhibit antibiotic stewardship behaviors. Participants' beliefs that they and the general public are responsible for causing and solving AR were lower than their beliefs that healthcare providers, scientists, and drug companies are responsible. Beliefs about causal responsibility for any given person or group were significantly and positively associated with beliefs about solution responsibility for that same person or group. Responsibility beliefs differed by age, education level, and racial/ethnic background. Results highlight the need for antibiotic stewardship campaigns to incorporate responsibility attribution messaging to motivate stewardship.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
ABSTRACT
We present an improved measurement of the Hubble constant (H0) using the ‘inverse distance ladder’ method, which adds the information from 207 Type Ia supernovae (SNe Ia) from the Dark ...Energy Survey (DES) at redshift 0.018 < z < 0.85 to existing distance measurements of 122 low-redshift (z < 0.07) SNe Ia (Low-z) and measurements of Baryon Acoustic Oscillations (BAOs). Whereas traditional measurements of H0 with SNe Ia use a distance ladder of parallax and Cepheid variable stars, the inverse distance ladder relies on absolute distance measurements from the BAOs to calibrate the intrinsic magnitude of the SNe Ia. We find H0 = 67.8 ± 1.3 km s−1 Mpc−1 (statistical and systematic uncertainties, 68 per cent confidence). Our measurement makes minimal assumptions about the underlying cosmological model, and our analysis was blinded to reduce confirmation bias. We examine possible systematic uncertainties and all are below the statistical uncertainties. Our H0 value is consistent with estimates derived from the Cosmic Microwave Background assuming a ΛCDM universe.
We present a catalog of galaxy clusters selected via their Sunyaev-Zel'dovich (SZ) effect signature from 2500 deg super(2) of South Pole Telescope (SPT) data. This work represents the complete sample ...of clusters detected at high significance in the 2500 deg super(2) SPT-SZ survey, which was completed in 2011. A total of 677 (409) cluster candidates are identified above a signal-to-noise threshold of xi = 4.5 (5.0). Ground- and space-based optical and near-infrared (NIR) imaging confirms overdensities of similarly colored galaxies in the direction of 516 (or 76%) of the xi > 4.5 candidates and 387 (or 95%) of the xi > 5 candidates; the measured purity is consistent with expectations from simulations. Of these confirmed clusters, 415 were first identified in SPT data, including 251 new discoveries reported in this work. We estimate photometric redshifts for all candidates with identified optical and/or NIR counterparts; we additionally report redshifts derived from spectroscopic observations for 141 of these systems. The mass threshold of the catalog is roughly independent of redshift above z ~ 0.25 leading to a sample of massive clusters that extends to high redshift. The median mass of the sample is M sub(500c)(rho sub(crit)) ~3.5 x 10 super(14) M sub(middot in circle) h super(-1) sub(70), the median redshift is z sub(med) = 0.55, and the highest-redshift systems are at z > 1.4. The combination of large redshift extent, clean selection, and high typical mass makes this cluster sample of particular interest for cosmological analyses and studies of cluster formation and evolution.
We present optical spectroscopy of galaxies in clusters detected through the Sunyaev-Zel'dovich (SZ) effect with the South Pole Telescope (SPT). We report our own measurements of 61 spectroscopic ...cluster redshifts, and 48 velocity dispersions each calculated with more than 15 member galaxies. This catalog also includes 19 dispersions of SPT-observed clusters previously reported in the literature. The majority of the clusters in this paper are SPT-discovered; of these, most have been previously reported in other SPT cluster catalogs, and five are reported here as SPT discoveries for the first time. By performing a resampling analysis of galaxy velocities, we find that unbiased velocity dispersions can be obtained from a relatively small number of member galaxies (lap30), but with increased systematic scatter. We use this analysis to determine statistical confidence intervals that include the effect of membership selection.We fit scaling relations between the observed cluster velocity dispersions and mass estimates from SZ and X-ray observables. In both cases, the results are consistent with the scaling relation between velocity dispersion and mass expected from dark-matter simulations. We measure a ~30% log-normal scatter in dispersion at fixed mass, and a ~10% offset in the normalization of the dispersion-mass relation when compared to the expectation from simulations, which is within the expected level of systematic uncertainty.
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