Partial Clearance Research Articles

A Randomized, Double-Blind, Placebo-Controlled, Multicentric Study to Evaluate the Efficacy and the Tolerability of a Class II Medical Device in the Treatment of Mild and Moderate Acne.

IntroductionSeveral options are available to treat acne lesions, including topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and procedural therapies, such as light and laser therapies, although these cause side effects. This study aimed to establish the efficacy and tolerability of a class IIa medical device containing lactic acid, azelaic acid/polyglyceryl-3 copolymer, azelamidopropyl dimethyl amine, and bifida ferment lysate for the treatment of mild and moderate acne lesions.MethodsA randomized, double-blind, placebo-controlled, multicentric study was carried out in which 60 persons of both genders aged ≥ 16 years affected by mild or moderate acne were enrolled. Each person used the product twice daily for 2 months. The clinical score (classified as absent, mild, moderate, and severe) of lesions such as blackheads, whiteheads, papules and pustules, erythema, desquamation, sebum secretion, and porphyrins production by a wood lamp was evaluated on the basis of a dermatologist’s visual assessment at baseline (t0) and after 2 months of treatment (t1), and the results were compared between groups. Digital photographic images were also taken.ResultsSixty subjects concluded the trial. It was observed that subjects treated with the medical device (group I) showed overall improvement in the analyzed acne lesions compared with placebo (group II) after 2 months of treatment. The efficacy of the treatment was also expressed as partial and total clearance. The medical device produced higher percentages of both partial and total clearance in all analyzed parameters, compared with the placebo group. The study was safe and well tolerated.ConclusionsIt was observed that the participants showed an overall improvement of the analyzed lesions in comparison with the placebo group, without adverse events during the trial. Hence, the medical device was found to be safe and effective in the treatment of mild or moderate acne.

274 Complete clearance of actinic keratosis observed from day 8 of tirbanibulin treatment, along with good tolerability: post-hoc analysis of two Phase 3 studies

Tirbanibulin 1% ointment was approved for actinic keratosis (AK) of face or scalp based on two Phase 3 trials. Pooled rates of complete (100%) clearance (CC) and partial (≥75%) clearance (PC) in these trials were reported for Day (D) 57 of treatment, being 49% and 72% respectively. We present post-hoc efficacy and safety analyses evaluating earlier time points.

Application of Urine and Copro Antigen Assays after Primary Infection and Drug Treatment in an Experimental Opisthorchiasis Animal Model.

Infection by Opisthorchis viverrini causes significant health problems, including cholangiocarcinoma (CCA); thus control and elimination of this trematode is an important strategy for the reduction of CCA. Currently, urine and copro antigen detection is more sensitive than parasitological examination of the feces for the diagnosis of opisthorchiasis. Given limitations in human studies, we used an animal model to quantify the parasite antigen profiles in urine and feces in O. viverrine-infected hamsters, and postdrug treatment. The positive detections of O. viverrini antigen began from week 1 in urine and week 2 in feces after infection until week 28 of the study. The recoveries of O. viverrini worms were detected starting from week 1 and eggs of O. viverrini were detected in feces from week 3 after infection and remained detectable throughout the study period. There was a significant positive correlation of urine and copro antigen levels with the number of fecal egg counts (P < 0.01) and worm recovery (P < 0.01). In the drug-treatment experiment, treatment of infected hamsters with praziquantel significantly reduced worm burden, fecal egg output, and antigen in urine and feces compared with the untreated controls (P < 0.001). At 4 weeks posttreatment, the egg and worm reduction rates were 100% and 95.5%, respectively. The positive antigen detections in urine and feces corresponded with partial worm clearance from praziquantel treatment. This study demonstrated a direct link of urine and copro antigen tests with worms infecting the liver thereby reaffirming the reliability of urine and copro antigen assay in opisthorchiasis diagnosis.

Use of a videofluoroscopic feeding evaluation to guide management of dogs with congenital idiopathic megaoesophagus.

BackgroundEvidence‐based guidelines for determining dietary management in dogs with megaoesophagus are lacking.ObjectivesThis study looked to compare oesophageal clearance times (ECT) of liquid and two food consistencies using a contrast videofluoroscopy feeding evaluation, and to assess if recommendations made based on findings could improve regurgitation and quality of life in dogs with congenital megaoesophagus.MethodsTwenty‐one dogs with congenital megaoesophagus and nine healthy dogs received liquid, slurry, and meatball diets containing barium while in an upright position. Follow‐up was performed to determine response to recommendations.ResultsHealthy dogs had significantly shorter median ECT for all consistencies (p < 0.001). In the megaoesophagus group, ECT varied by consistency and individual. The number of dogs in the megaoesophagus group with complete clearance was four (median ECT 10 min) for liquid, five (median ECT 5 min) for slurry, and two (median ECT 5 and 30 min, respectively) for meatballs. Partial clearance was seen in 11 dogs (median clearance 25%) with liquid, seven with slurry (median clearance 50%), and five with meatballs (median clearance 60%). Recommendations included altering current medications (13/21 dogs), diet consistency (6/21), time upright (12/21), water delivery (21/21), and adding activity (7/21). Regurgitation episodes/week decreased significantly from 5.5 to 2.5 (p < 0.001) at follow‐up 3–5 weeks post‐evaluation, with 95% of owners reporting improvement in quality of life. Seventy percent were alive 46–777 days after last recheck. Three dogs died from megaoesophagus associated complications (median survival 461 days after diagnosis).ConclusionsThe findings of this study suggest that a videofluoroscopic feeding evaluation may help guide management of dogs with congenital megaoesophagus.

Early clinical response to 5-fluorouracil 0.5% and salicylic acid 10% topical solution in the treatment of actinic keratoses of the head: an observational study

Background Actinic keratosis is one of the most common dermatological disorders. A new topical solution, constituted by 0.5% 5-fluorouracil and 10% salicylic acid (Actikerall, Almirall) has been introduced in the treatment pipeline of hyperkeratotic actinic keratoses of the head and neck. Patients and methods We analyzed in an observational prospective clinical study the short-term treatment effectiveness of 5-fluorouracil and salicylic acid on face and scalp actinic keratoses of grade 1 and 2 of 40 patients. Efficacy assessment was performed by clinical dermatological examination, collecting color photographs, calculating AKASI score, and by means of dermoscopy for each target lesion at every visit. Results AKASI score decreased from an initial score of 3.3 to a final score of 0.9. At week 4, we were able to record a complete clearance of 50% of the treated lesions and a partial clearance of 28%. At the end of 12 weeks, 84% of the total lesions showed complete clearance, while 8% had partial clearance. Conclusions 5-fluorouracil and salicylic acid topical solution is effective in the treatment of mild to moderate actinic keratoses. In the future, further studies are needed to evaluate the chance of adjusting drug dosage according to patients' and actinic keratoses features.

Intense Pulsed Light Therapy Improves Acne-Induced Post-inflammatory Erythema and Hyperpigmentation: A Retrospective Study in Chinese Patients.

IntroductionPost-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH) are the most common acne-related sequelae with no effective treatments. By combining different cut-off filters, intense pulsed light (IPL) therapy can effectively treat these conditions with few side effects. While the safety and effectiveness of IPL for treating post-burn hyperpigmentation is well known, there is little evidence for its benefits for acne-related PIH. In this article, we evaluate the efficacy and safety of IPL for the treatment of acne-related PIE and PIH.MethodsThis retrospective study evaluated 60 patients with more than 6 months of PIE and PIH treated by the same IPL device and similar protocols. The treatment included three to seven sessions at 4–6-week intervals, and three cut-off filters (640 nm, 590 nm and 560 nm) were used sequentially in each session. Using the Global Aesthetic Improvement Scale (GAIS), Cardiff Acne Disability Index (CADI), and Erythema Assessment Scale (EAS), patients were evaluated on the basis of their facial photographs. The facial brown spots and red areas were visualised and analysed using the VISIA-CR system. Six months after the last treatment, the patients were assessed for acne relapse or any side effects.Please check and confirm that the authors and their respective affiliations have been correctly processed and amend if necessary.Checked and confirmed. No further corrections.ResultsOn the basis of the GAIS, 49 of 60 patients (81.7%) showed complete or partial clearance of erythema and hyperpigmentation. The CADI and EAS scores showed significant improvement (p < 0.01) after IPL treatment compared with pre-treatment. A significant reduction (p < 0.01) in the facial brown spots and red areas was seen after IPL treatment. While no long-term side effects were reported, seven patients (11.7%) experienced acne relapse at follow-up.ConclusionIPL is an effective and safe treatment for acne-related PIE and PIH.

Controlling trapping, overgrazing and invasive vegetation is key to saving Java’s last population of the Black-winged Myna

AbstractThe Black-winged Myna (Acridotheres melanopterus) is an Endangered passerine endemic to the islands of Java and Bali, Indonesia. Illegal trapping to supply the cage-bird trade has led to its near-total extinction, with the global population estimated to number fewer than 100 individuals. We estimated the current range and population size of the species at Baluran National Park, which supports Java’s last known population, and used species distribution modeling to evaluate potential suitability of currently unoccupied areas across the park to identify priorities for management intervention. We estimate that the Black-winged Myna population numbers 179 individuals (95% CI: 111–288; density: 14.3 ± 3.5 individuals km–2) and that its current range is 12.3 km2. Our model indicated that some 72 km2 of the park (30% of total area) has potentially suitable habitat for the species, and we infer that the principal cause for the disparity between its current and potential range is trapping, compounded by savanna loss and degradation due to illegal domestic cattle grazing and the spread of invasive thorny acacia (Vachellia nilotica). The partial clearance of acacia in recent years appears to have assisted a modest population recovery by the myna. Its further population growth and range expansion in Baluran will depend on effective management of illegal poaching, further clearance of acacia, and easing domestic cattle grazing pressure on areas of savanna, particularly through engagement with communities living inside the park. Any actions that increase the size of the Black-winged Myna population are likely to benefit other threatened savanna-dependent wildlife in the park, notably banteng (Bos javanicus) and Green Peafowl (Pavo muticus). While our models and recommendations may be applicable to other protected areas in Java, and indeed other threatened myna species, trapping and habitat change may have site-specific dimensions, especially outside of protected areas, and thus demand local bespoke solutions.

Ubr1-induced selective endophagy/autophagy protects against the endosomal and Ca2+-induced proteostasis disease stress

The cellular defense mechanisms against cumulative endo-lysosomal stress remain incompletely understood. Here, we identify Ubr1 as a protein quality control (QC) E3 ubiquitin-ligase that counteracts proteostasis stresses by facilitating endosomal cargo-selective autophagy for lysosomal degradation. Astrocyte regulatory cluster membrane protein MLC1 mutations cause endosomal compartment stress by fusion and enlargement. Partial lysosomal clearance of mutant endosomal MLC1 is accomplished by the endosomal QC ubiquitin ligases, CHIP and Ubr1 via ESCRT-dependent route. As a consequence of the endosomal stress, a supportive QC mechanism, dependent on both Ubr1 and SQSTM1/p62 activities, targets ubiquitinated and arginylated MLC1 mutants for selective endosomal autophagy (endophagy). This QC pathway is also activated for arginylated Ubr1-SQSTM1/p62 autophagy cargoes during cytosolic Ca2+-assault. Conversely, the loss of Ubr1 and/or arginylation elicited endosomal compartment stress. These findings underscore the critical housekeeping role of Ubr1 and arginylation-dependent endophagy/autophagy during endo-lysosomal proteostasis perturbations and suggest a link of Ubr1 to Ca2+ homeostasis and proteins implicated in various diseases including cancers and brain disorders.

Efficacy of extracorporeal shock wave lithotripsy of pancreatic stone in chronic pancreatitis

Background: To study overall outcome of ESWL therapy in large pancreatic duct stone as first line therapy in chronic pancreatitis.Methods: A prospective, observational study which took place in MGM medical college and the patient were admitted in general surgery department. Patients were selected based on the inclusion criteria composed of upper abdominal pain, weight loss, oily stools and presence of pancreatic stones or ductal irregularity/ parenchymal atrophy determined by various radiological investigations.Results: In this study 11 patients with pancreatic stones were recruited in duration of 2 years. Among 11 patients included in this study 63.33% were males and 36.375% were females. The mean age of males and females were 35.57 and 40.50 years respectively. It was observed that all study subjects had abdominal pain and history of pancreatitis. 36% patient had single calculi and 64% patient had multiple calculi. 18% calculi were present in the body of pancreas and 46% calculi in head of pancreas. All these patient had undergone ESWL procedures with minimum number of 400 shocks and maximum number of 4600. Among the patients it was noted that 73% had successful complete clearance of calculi, 18% had partial clearance and 9% had no clearanceConclusions: ESWL is efficient tool for the treatment of pancreatic calculi but can be used alone it is adjunct tool to ERCP. Endoscopy, etc.

COVID vaccine‐induced reaction around molluscum contagiosum with secondary partial clearance of lesions

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Efficacy of sunscreen with photolyase or regular sunscreen associated with topical antioxidants in treating advanced photodamage and cutaneous field cancerization: a randomized clinical trial

BackgroundSeveral treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK). ObjectivesEvaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage. MethodsThis was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety. ResultsForty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them. Study limitationsShort interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study. ConclusionsThere is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo.

10% Thioglycolic Acid Peel in the Treatment of Pigmented Purpuric Dermatoses: A Pilot Study.

Pigmentary purpuric dermatosis (PPD) is a chronic dyspigmentation characterized by reddish-brown, irregular maculae with dermal hemosiderin deposition, usually affecting the legs. The -SH group in the thioglycolic acid (TGA) strongly binds to iron molecule, solubilizes it, and clears the pigment. We conducted a longitudinal, right-left leg study for assessing the effectiveness and side effects of TGA 10% peel in treating PPD. For preparation of 10% TGA peel, 80% TGA was diluted with distilled water to 10% concentration by mixing 0.5 mL of acid with 3.5 mL of water before every peel session. The peel was applied on the left leg, weekly for 6 weeks. Assessment was done at baseline and at weeks 3 and 6. Any improvement was noted by the patient and another independent dermatologist. The right leg was untreated. Any side effects during peel application and afterwards were noted. According to the patient assessment, 4/10 patients observed mild improvement, 5/10 patients had moderate improvement, and only a single patient had marked improvement. In the physician assessment, 2/10 patients had >50% improvement, 5/10 patients had 30-40% improvement, and 3/10 patients had 10-20% improvement. Side effects included slight burning during application and foul odor. A single patient had intense erythema and mild swelling of the leg after peel application. 10% TGA is effective in the partial clearance of PPD dyspigmentation with weekly sessions for 6 weeks without any serious side effects.

A study to evaluate the efficacy and safety of intradermal and intralesional Purified Protein Derivative (PPD) for treatment of common warts in children

: Viral warts are common dermatological diseases with wide range of treatment modalities. Utilization of various vaccines and skin test antigens has broadened the horizon of available immunotherapeutic agents for the treatment of warts. In this study, we compared efficacy and safety of intradermal and intralesional purified protein derivative (PPD) for treating common warts in children.Toevaluate efficacy and safety of intradermal and intralesional PPD in treatment of common warts in children.: 180 children (aged 5-15 years) with common warts were randomly divided to receive intradermal (n=90) PPD 10 TU/0.1 ml at middle third of right forearm or intralesional PPD (n=90) 0.1 ml in the largest wart once in 2-weeks till there is complete clearance or maximum of five injections whichever is earlier. Patients were followed at 4 week after last injection for assessment of response, adverse effects, and recurrence of common warts.: Complete, partial clearance and no response in 51.2%, 45.3% and 2.3% children was observed in intradermal group as compared to 54.2%, 42.5% and 1.1% response in intralesional group respectively. Recurrence of warts was observed in 1.2% and 2.2% children in intradermal and intralesional group respectively. Pain was the most common adverse effect in both groups followed by erythema lasting for 2-3 days not warranting for discontinuation of treatment in any patient.: Overall 96.5% and 96.7% patients in both intradermal and intralesional group responded to treatment respectively. We conclude that immunotherapy with PPD appears safe, effective, and acceptable treatment modality for common warts in children. Although intralesional group showed slightly higher efficacy for warts (0.2%), intradermal PPD has advantage of less pain, high patient satisfaction, less spillage of injection material onto surroundings and better compliance over intralesional group and hence can be considered as valuable first line treatment in children in resource poor developing countries.

Pancreatoscopy-guided electrohydraulic lithotripsy for the treatment of obstructive pancreatic duct stones: a prospective consecutive case series

Pancreatoscopy-guided electrohydraulic lithotripsy (EHL) has shown potential in the treatment of patients with obstructive chronic calcifying pancreatitis (CCP). We aimed to prospectively investigate the efficacy and safety of EHL as first-line therapy in patients with CCP of the pancreatic duct (PD). A prospective single-center consecutive case series was performed including symptomatic CCP patients with obstructing stones >5mm in the head or neck of the pancreas. Stone fragmentation was performed using EHL. Primary study outcome was technical success. Secondary outcomes were clinical success, adverse events, and number of interventions. Thirty-four consecutive patients were included. Complete or partial stone clearance after EHL was achieved in 24 patients (70.6%). Pancreatoscopy was not performed because of failure to cannulate the PD (n= 5) or resolution of stones after stent placement at the index endoscopic retrograde pancreaticography (ERP) procedure (n= 3). After successful PD cannulation, pancreatoscopy was technically successful in 24 of 26 patients (92.3%). In 1 patient, the stone could not be visualized because of a resilient stricture. Complete stone clearance was achieved in 20 patients (80%) and partial clearance in 5 patients (20%), after a median of 2 ERP procedures (interquartile range, 2) and 1 EHL procedure (interquartile range, 1). In patients who underwent pancreatoscopy with EHL, mean Izbicki pain score at baseline was 62.3 ± 23.1 (25/25) and dropped significantly to 27.5 ± 35.0 (22/25) at the 6-month follow-up (P< .001). The most common adverse event was acute pancreatitis, all mild and treated conservatively (n= 7). Pancreatoscopy-guided EHL is a promising treatment for symptomatic CCP patients with obstructive PD stones. (Clinical trial registration number: NTR6853.).

Effect of migalastat on cardiac involvement in Fabry disease: preliminary results from MAIORA study

Abstract Background Fabry Disease (FD) is a rare X-linked lysosomal storage disorder. Since 2016, pharmacological chaperone Migalastat has been approved for treatment of FD patients with amenable mutations to stabilize defective forms of the enzyme α-galactosidase A. A small but significant reduction in left ventricular (LV) mass after 18 months of Migalastat treatment has been previously reported by echocardiography. However, an integrated assessment of the effect of Migalastat on cardiac involvement, combining LV morphology and tissue composition by CMR with exercise capacity by cardiopulmonary test, is lacking. Purpose To determine the effects of 18 month treatment with Migalastat on LV mass, native T1 value and functional capacity in naïve patients with genetically confirmed FD cardiomyopathy. Methods Sixteen treatment naïve FD patients (4 females, mean age 46.4±16.2) with amenable mutations and signs of cardiac involvement underwent CMR with T1 mapping and cardio-pulmonary testing before and after 18 months of migalastat therapy as a part of MAIORA Study. Cardiac involvement was defined as presence of reduced native T1 values at CMR (a surrogate of myocardial glycosphingolipid storage) and/or LV hypertrophy (LVH). Nine patients (56%, 2 females, mean age 56.4±12.7 years) had LVH at baseline. Results Migalastat treatment was well tolerated in all patients, with no serious adverse event. No change in LV mass was detected at 18 months compared to baseline (95.2 (66.0–184.0) vs 103.0 (71.0–182.0) g/m2; p=0.5516). The same result was found after stratifying patients according to presence/absence of Late Gadolinium Enhancement (LGE) (LGE+ n=8, 2 females, mean age 56.2±13.1 years). There was a trend towards an increased native septal T1 value (870.0 (848–882) vs 860.0 (833.0–875.0) ms at baseline; p 0.056) with unchanged extracellular volume (ECV) (0.26 (0.23–0.028) vs 0.26 (0.22–0.29) at baseline; p 0.276) in the overall cohort. An improvement in functional capacity with a trend towards an increase in percent-predicted peak VO2 (72.0 (61.25–80.75) vs 67.0 (45.2–79.2) at baseline; p 0.056) and a significant increase in VO2 at anaerobic threshold (14.8 (12.6–20.0) vs 13.10 (6.8–18.6) ml/kg/min at baseline; p 0.004) was reported in the total population. Conclusion In treatment naïve FD patients with amenable mutations and signs of early or overt cardiac involvement, 18-month treatment with Migalastat stabilized LV mass both in patients with and without LGE and was associated with an improvement in exercise tolerance. The trend towards an increase in T1 value associated with unchanged ECV suggests partial clearance of cardiomyocyte glycoshingolipid storage. These real-world data are consistent with a beneficial impact of migalastat on the progression of cardiac involvement in FD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus Therapeutics

A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis.

IntroductionActinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as “field of cancerization,” which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions.MethodsSeventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3 months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated.ResultsThere was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Kerà K2 group than in the placebo group (−42.78, SD 26.53, versus −6.20, SD 31.57), and the difference was statistically significant (p < 0.001). For 70 subjects (56.7%) in the Kerà K2 group and 3 (11.54%) in the placebo group, a significant (p < 0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups.ConclusionsThe medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.

Evaluation of Long-term Clearance Rates of Interventions for Actinic Keratosis

Multiple interventions are available for the treatment of actinic keratosis (AK). However, most randomized clinical trials and meta-analyses focus on short-term efficacy outcomes. To investigate and synthesize the long-term efficacy (≥12 months) of interventions for AK from parallel-arm randomized clinical trials. Searches in MEDLINE, Embase, and Central were conducted from inception until April 6, 2020. The reference lists of the included studies and pertinent trial registers were hand searched. The study was completed February 27, 2021. Two reviewers screened the titles and abstracts of 2741 records. Finally, 17 published reports (original studies and follow-up reports) referring to 15 independent randomized clinical trials with an overall sample size of 4252 patients were included. Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analysis (NMA) of each outcome was conducted with a frequentist approach. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidance for NMA was used to assess the certainty of evidence. The revised Cochrane risk-of-bias tool for randomized clinical trials was used to evaluate the methodologic quality. Participant complete clearance, participant partial clearance, and lesion-specific clearance were the outcomes, with each assessed at least 12 months after the end of treatment. Data from 15 independent randomized clinical trials including 4252 patients were extracted and synthesized. Ten studies were included in an NMA for the outcome of participant complete clearance, with photodynamic therapy with aminolevulinate (ALA-PDT) showing the most favorable risk ratio (RR) compared with placebo (RR, 8.06; 95% CI, 2.07-31.37; GRADE, moderate), followed by imiquimod, 5% (RR, 5.98; 95% CI, 2.26-15.84; GRADE, very low), photodynamic therapy with methyl aminolevulinate (MAL-PDT) (RR, 5.95; 95% CI, 1.21-29.41; GRADE, low), and cryosurgery (RR, 4.67; 95% CI, 1.36-16.66; GRADE, very low). Similarly, ALA-PDT had the highest RR in the NMA for lesion-specific clearance (RR, 5.08; 95% CI, 2.49-10.33; GRADE, moderate). No NMA was possible for participant partial clearance owing to poor reporting of this outcome. This systematic review and network meta-analysis found that therapy including ALA-PDT, imiquimod, 5%, MAL-PDT, and cryosurgery was associated with significant long-term efficacy in the NMA. This study provides data for a possible use in an evidence-based framework for selecting interventions with sustained lesion clearance.

Treatment of mycosis fungoides: results from a large international study

British Journal of DermatologyVolume 184, Issue 4 p. e129-e129 Plain Language Summary Treatment of mycosis fungoides: results from a large international study First published: 09 April 2021 https://doi.org/10.1111/bjd.19840AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Mycosis fungoides is a type of blood cancer. The early phases of mycosis fungoides are represented by patches (flat lesions) or plaques (solid lesions) on the skin. Treatment usually consists of topical steroid creams, phototherapy (using ultraviolet light) or radiotherapy (using radiation). Together these methods are called skin-directed treatments. This study enrolled 395 patients with a new diagnosis of mycosis fungoides from 41 centres across 17 countries in Europe, North and South America, and Australia. The results show that the majority of patients (82%) received skin-directed treatment as the first medication, while 11% first received tablets or injections. Patients who were treated first with tablets or injections showed more severe disease, plaques more frequently than patches, thicker skin lesions, and mycosis fungoides involving hair follicles. The presence of plaques was associated with a worse outcome and lower response to therapy. We also showed that half of these patients had significantly reduced quality of life, which improved after treatment. The proportion of patients who achieved a complete or partial clearance of the skin lesions was 67%. Overall, 73% more people receiving skin-directed treatments responded to therapy than those receiving tablets or injections. This means that it is generally preferable to start therapy with skin-directed treatment in most cases. This study suggests that treatment of patients with early-stage mycosis fungoides should focus on patients with high-risk skin features and evaluation of quality of life. Linked Article: Quaglino et al. Br J Dermatol 2021; 184:722–730. Volume184, Issue4April 2021Pages e129-e129 RelatedInformation

Laryngeal function in normal dogs administered isoflurane following partial clearance of alfaxalone or propofol

ObjectiveTo assess laryngeal function in normal dogs administered isoflurane following partial clearance of alfaxalone or propofol. Study designRandomized experimental crossover study. AnimalsA group of 12 purpose-bred, male Beagle dogs. MethodsDogs were randomly assigned to one of two treatments: alfaxalone–isoflurane (ALF-ISO) or propofol–isoflurane (PRO-ISO) and anesthetized for three video laryngoscopy examinations. The alternate treatment occurred after ≥ 14 days interval. Examinations were performed after induction of anesthesia (LS-A), after 20 minutes of breathing isoflurane via a facemask (LS-B) and after a further 20 minutes of isoflurane (LS-C). Parameters of objective laryngeal function included inspiratory rima glottidis surface area (RGSA-I), expiratory rima glottidis surface area (RGSA-E) and % RGSA increase, calculated from three consecutive respiratory cycles in the final 15 seconds of each video laryngoscopy examination. The % RGSA increase was calculated using [(RGSA-I – RGSA-E)/RGSA-E] × 100. Subjective laryngeal function was evaluated independently by two experienced surgeons blinded to treatment. ResultsThe % RGSA increase within each treatment was greater for LS-B and LS-C than for LS-A (ALF-ISO: p = 0.03, PRO-ISO: p = < 0.001). There was no difference within each treatment from LS-B compared with LS-C. RGSA-I increased within each treatment from LS-A to both LS-B and LS-C (ALF-ISO: p = 0.002) and to LS-C (PRO-ISO: p = 0.006). Subjective laryngeal function scores improved from LS-A to LS-C. Conclusions and clinical relevanceLaryngeal function improved from postinduction examination following either 20 or 40 minutes of anesthesia with isoflurane via facemask. This study demonstrates that isoflurane may have a lesser effect on arytenoid abduction activity compared with more commonly used intravenous induction anesthetics (alfaxalone and propofol).

Dosing of Direct Oral Anticoagulants in Patients with Moderate Chronic Kidney Disease in US Clinical Practice: Results from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF II).

Direct oral anticoagulants (DOACs) have partial renal clearance and generally require dosage adjustments based on renal function. While current US and European guidance recommends dose adjustments in patients with moderate chronic kidney disease (CKD), it is unclear how often this is done appropriately in routine clinical practice. We examined rates of appropriate and inappropriate dosing in patients with atrial fibrillation (AF) and moderate CKD, as determined by creatinine clearance (CrCl) of 30-50 mL/min calculated with the Cockcroft-Gault formula. Descriptive statistics were used to describe the rate of appropriate and inappropriate dosing as well as event rates. Among 1134 patients (8.5% of the overall ORBIT-AF II registry) with AF and CrCl 30-50 mL/min, the median age was 82 (25th, 75th percentile: 78, 86), 38% were male, and the median CHA2DS2VASC score was 4 (25th, 75th percentile: 4, 5). At baseline, more than one-third (34%) of patients with moderate CKD were inappropriately dosed with DOACs. When evaluating the specific prescribed doses in those with moderate CKD, 15% (N = 170/1134) were underdosed, 66% (743/1134) were appropriately dosed, and 20% (N = 221/1134) were overdosed. There were no significant differences in comorbid medical conditions between patients with moderate CKD who were appropriately and inappropriately dosed with a DOAC. In routine clinical practice, prescribing of DOACs in patients with AF with moderate CKD is often inconsistent with drug labeling, with up to one-third of patients being inappropriately dosed.