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Background: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long‐term data on JAK inhibitors in AA. Objectives: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. Methods: Integrated data from the BRAVE‐AA1 and BRAVE‐AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2‐mg or 4‐mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week‐52 responders; 2‐mg: N = 65; 4‐mg: N = 129) and baricitinib 4‐mg‐treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week‐52 mixed responders; N = 110). Week‐104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. Results: Among baricitinib 4‐mg‐treated and baricitinib 2‐mg‐treated Week‐52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week‐52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment‐emergent adverse events were COVID‐19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. Conclusions: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week‐52 mixed responders, illustrating that long‐term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

Byline: P. Parikh, S. Gupta, S. Dawood, H. Rugo, G. Bhattacharyya, A. Agarwal, R. Chacko, T. Sahoo, G. Babu, S. Agarwal, A. Munshi, C. Goswami, B. Smruti, S. Bondarde, C. [...]

BACKGROUND: Targeting of VEGF is a potential therapeutic option in patients with malignant ovarian ascites. We present the final results of a multicentre study of the efficacy and safety of aflibercept, a potent inhibitor of both VEGF and placental growth factor, in the treatment of malignant ascites. METHODS: In this double-blind, placebo-controlled, parallel-group, phase 2 study, patients with advanced chemoresistant ovarian cancer and recurrent symptomatic malignant ascites were randomly assigned (1:1) via an interactive voice response system to either intravenous aflibercept (4 mg/kg every 2 weeks) or placebo, stratified by interval of time (<=2 weeks vs >2 weeks) between the two most recent paracenteses before randomisation. Patients participated in the double-blind period (during which patients, investigators, and sponsor personnel were masked to treatment assignment) until they had a repeat paracentesis and for at least 60 days, and could also participate in an optional open-label period during which all patients received aflibercept. The primary efficacy endpoint was time to repeat paracentesis based on response during the double-blind period alone, and was analysed in the intention-to-treat population with censoring of patients who did not have a repeat paracentesis as of the last day of the double-blind period. Safety analyses included both double-blind and open-label periods. This study is registered at ClinicalTrials.gov, number NCT00327444. FINDINGS: 55 patients with a median of four (range two to 11) previous lines of chemotherapy were randomly assigned to receive placebo (n=26) or aflibercept (n=29). Mean time to repeat paracentesis was significantly longer with aflibercept than with placebo (55·1 [SE 7·3] vs 23·3 [7·7] days; difference 31·8 days, 95% CI 10·6-53·1; p=0·0019). In the aflibercept group, two patients did not need a repeat paracentesis during 6 months of double-blind treatment. The most common grade 3 or 4 treatment-emergent adverse events were dyspnoea (six [20%] aflibercept vs two [8%] placebo), fatigue or asthenia (four [13%] vs 11 [44%]), and dehydration (three [10%] vs three [12%]). The frequency of fatal gastrointestinal events was higher with aflibercept (three intestinal perforations) than with placebo (one intestinal fistula leading to sepsis). INTERPRETATION: This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites, but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer. VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis, and the benefit-risk balance should be thoroughly discussed for each patient. FUNDING: Sanofi Oncology. [ABSTRACT FROM AUTHOR]

Background: Baricitinib, an oral selective Janus kinase inhibitor, is approved to treat adults with severe alopecia areata (AA)., Objective: To report the week 152 efficacy results from the phase 3 trial BRAVE-AA2 down-titration substudy., Methods: BRAVE-AA2 enrolled 546 adults with severe AA (Severity of Alopecia Tool [SALT] score ≥50). Baricitinib 4-mg-treated patients achieving a clinical response (SALT score ≤20) at week 52 were rerandomized 1:1 to stay on 4-mg or down-titrate to 2-mg. The last observation carried forward was used to impute missing or censored data., Results: At week 52, 86/234 (36.8%) baricitinib 4-mg-treated patients were eligible for down-titration; 44 remained on 4-mg while 42 down-titrated to 2-mg. At week 152, 39/44 (88.6%) 4-mg-treated patients had maintained clinical response, compared to 24/41 (58.5%) down-titrated patients. Among down-titrated patients, loss of treatment benefit was less frequent in those with sustained response and SALT score ≤5 at week 52., Limitations: Method and timing of down-titration were prespecified in the protocol based on week 52 responder status and not on other clinical factors., Conclusion: More than half of down-titrated patients maintained response. Sustained treatment response and/or near-total regrowth may be associated with a greater likelihood of response maintenance after down-titration., Competing Interests: Conflicts of interest Dr King is a clinical trial investigator for Abbvie, Eli Lilly and Company, Incyte, Pfizer Inc, Regeneron, and Sanofi Genzyme; is a consultant or is on the advisory board for Abbvie, AltruBio Inc, Almirall, AnaptysBio, Arena Pharmaceuticals, Aslan Pharmaceuticals, BiologicsMD, Bristol Meyers Squibb, Concert Pharmaceuticals Inc, Equillium, Horizon Therapeutics, Eli Lilly and Company, Incyte Corp, Janssen Pharmaceuticals, LEO Pharma, Merck, Otsuka/Visterra Inc, Pfizer Inc, Q32 Bio Inc, Regeneron, Sanofi Genzyme, Sun Pharmaceutical Industries, TWi Biotechnology Inc; is on the data monitoring committee for Incyte Corp, Ventyx Biosciences Inc; is on speakers bureaus for Abbvie, Eli Lilly and Company, Incyte, Pfizer Inc, Regeneron, Sanofi Genzyme; and receives travel support from Pfizer, Eli Lilly and Company, Sun Pharmaceuticals. Dr Ohyama is a consultant or is on the advisory board for AbbVie GK, Bristol Myers Squibb Japan, Eli Lilly and Company, Maruho Pharmaceutical Co, Pfizer Inc, ROHTO Pharmaceutical Co, Taisho Pharmaceutical Co; is an editor at The Journal of Dermatology; reports honoraria/speakers bureaus for Eli Lilly and Company, Pfizer Inc; receives research grant from Shiseido Co, Maruho Co, Advantest Corp., Sun Pharma Japan Ltd; and receives travel support from Pfizer Inc. Dr Senna is a consultant or is on the advisory board for Abbvie, Eli Lilly and Company, Pfizer Inc, Arena, Cassiopia, Inmagene, Kintor, LOreal; is on the data monitoring committee for Abbvie, Eli Lilly and Company, Pfizer Inc; reports honoraria/speakers bureaus for Eli Lilly and Company, Pfizer Inc; receives travel support from Eli Lilly and Company, Pfizer Inc. Dr Shapiro is a consultant or is on the advisory board for Pfizer Inc, Eli Lilly and Company; Drs Dutronc, Durand, Yu, Kolodsick, and Chiasserini are employees and shareholders of Eli Lilly and Company. Dr Liu is an employee of Tigermed-BDM, Inc. Dr Piraccini is a consultant or is on the advisory board for Difa Cooper, Ducrey, Eli Lilly and Company, LOreal, Pfizer, Inc; reports honoraria/speakers bureaus for Difa Cooper, Ducrey, Eli Lilly and Company, LOreal, Pfizer, Inc. Dr Somani has no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth., Objective: To report results from the randomized withdrawal period of the BRAVE-AA1 trial., Design, Setting, and Participants: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023., Intervention: At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose., Main Outcome and Measures: The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data., Results: Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment., Conclusions and Relevance: Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth., Trial Registration: ClinicalTrials.gov Identifier: NCT03570749.

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment., Methods: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported., Results: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years., Conclusions: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life., Clinical Trial Numbers: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3)., (© 2024. The Author(s).)

Background: Baricitinib, an oral selective JAK1/JAK2 inhibitor, is approved for the treatment of adults with severe alopecia areata (AA)., Objective: To evaluate differences in response up to week 52 among subgroups based on the baseline severity of AA assessed with the Severity of Alopecia Tool (SALT) score., Methods: Data were pooled from BRAVE-AA1 and BRAVE-AA2, two randomized, placebo-controlled, phase 3 trials, which enrolled adults with a SALT score ≥ 50. Patients were subdivided by the degree of AA severity at baseline., Results: Among the 855 patients treated with baricitinib 2 mg and 4 mg, improvements in scalp hair growth continued through to week 52. A superior response was observed in patients with a SALT score of 50-94 versus a score of 95-100. Patients on baricitinib 4 mg had a faster and higher response rate compared to baricitinib 2 mg., Conclusion: Across all degrees of severity for baricitinib 2 mg and 4 mg doses, the proportion of patients responding was yet to plateau up to week 52. Response to treatment was longer for patients with a baseline SALT score 95-100. Further studies are needed to analyze other parameters that may impact observed response rates., (© 2023. The Author(s).)

Background: Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations., Objectives: To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups., Methods: The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported., Results: Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss., Conclusions: These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth., Competing Interests: Conflicts of interest B.K. has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AbbVie, AltruBio, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Myers Squibb, Concert Pharmaceuticals, Equillium, Horizon Therapeutics, Eli Lilly and Company, Incyte, Janssen Pharmaceuticals, LEO Pharma, Otsuka/Visterra, Pfizer, Regeneron, Sanofi-Genzyme, TWi Biotechnology and Viela Bio; and has served on speaker bureaus for AbbVie, Eli Lilly and Company, Incyte, Pfizer, Regeneron and Sanofi Genzyme. J.S. has received travel reimbursement and speaking honoraria from Eli Lilly and Company. M.O. has received lecture fees from Eli Lilly and Company and advisory fees from Eli Lilly and Company, Pfizer, Janssen Pharmaceuticals (Japan), Taisho Pharmaceutical, Maruho, Bristol Myers Squibb Japan, AbbVie and ROHTO Pharmaceutical; and grants/research funds from Shiseido, Maruho, Advantest and Sun Pharma Japan. He is a specialist associate editor of the British Journal of Dermatology and was excluded from all editorial decision-making related to the acceptance of this article for publication. A.E. has received research funding from Pfizer, Eli Lilly and Company, Novartis, Bristol Myers Squibb, Boehringer Ingelheim, AbbVie, Janssen Pharmaceuticals, Boehringer Ingelheim, the Danish National Psoriasis Foundation, the Simon Spies Foundation and the Kgl Hofbundtmager Aage Bang Foundation; and honoraria as a consultant and/or speaker from AbbVie, Almirall, Amgen, Boehringer Ingelheim, LEO Pharma, Zuellig Pharma, Galápagos, Sun Pharmaceuticals, Samsung Bioepis, Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim and Janssen Pharmaceuticals. B.M.P. has received lecture fees from Eli Lilly and Company and Pfizer; consulting fees from Eli Lilly and Company, Pfizer, ISDIN, Almirall and Vichy; and has participated in advisory boards for Eli Lilly and Company and Pfizer. B.C. has received honoraria and/or fees from Eli Lilly and Company, Pfizer, Regeneron and Sanofi-Genzyme. R.S. reports serving as a consultant or paid speaker for or participating in clinical trials sponsored by LEO Pharma, Amgen, Novartis Pharmaceuticals, Merck & Co, Celgene, Coherus BioSciences, Janssen Global Services, Regeneron Pharmaceuticals, MedImmune, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingelheim, Pfizer, Merck Sharpe & Dohme, Oncobiologics, F. Hoffmann-La Roche, Eli Lilly and Company, and Bayer; and is serving as the current President of the Australasian Hair and Wool Research Society. Y.-F.C., W.-S.W, Y.D., N.S. and Y.D. are employees of and shareholders in Eli Lilly and Company., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objectives: The objectives of this review were to identify the types of music-based interventions and associated accessibility challenges for people who have visual impairment (VI) and their reported effects on psychological, physiological and social well-being., Design: A scoping review was developed according to the Joanna Briggs Institute methodology and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist and guidelines. A narrative synthesis was conducted to map out the types of music-based interventions undertaken and to compare the therapeutic outcomes. The studies were evaluated according to the music reporting checklist., Results: In total 5082 records were identified, 69 full-text articles were screened and 13 studies were included. Eleven studies included younger children and teenagers, two focused on adults with acquired VI. Ten studies involved active music therapy strategies and three used passive music listening. Eleven of the studies focused on social outcomes and two reported mental health. Although the studies reported that music-based intervention strategies improved psychosocial well-being in people with a VI, conclusions could not be drawn as robust outcome measures were not generally used and only four of the studies included any statistical analysis., Conclusions: Although potential was evident, details of intervention protocols and training requirements were not sufficiently reported and further, high-quality evidence-based studies are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Baricitinib is an oral selective Janus kinase 1/2 inhibitor that has achieved clinically meaningful outcomes for scalp, eyebrow, and eyelash hair regrowth in patients with severe alopecia areata (AA) at week 36 of treatment. Treatment with baricitinib, 4 mg, has resulted in higher response rates than baricitinib, 2 mg, at weeks 36 and 52., Objective: To determine the efficacy of uptitration to baricitinib, 4 mg, for 24 weeks in patients who had previously not responded to baricitinib, 2 mg (Severity of Alopecia Tool [SALT] score of >20)., Design, Setting, and Participants: BRAVE-AA1 and BRAVE-AA2 are multicenter, placebo-controlled, phase 3 randomized clinical trials that were initiated on September 24, 2018, and July 8, 2019, respectively, with follow-up to 200 weeks (data cutoffs of November 11, 2021, and November 5, 2021, respectively). This pooled analysis reports long-term extension data up to week 76. At baseline, 1200 adult patients with severe AA (SALT score ≥50) were randomly assigned in a 3:2:2 ratio to receive baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Patients treated with baricitinib remained on the same treatment dose until week 52. Patients were considered nonresponders to baricitinib, 2 mg, if they had a SALT score greater than 20 after 52 weeks of therapy., Main Outcomes and Measures: The proportions of patients achieving a SALT score of 20 or lower and clinician-reported outcome for eyebrow hair loss and eyelash hair loss scores of 0 or 1 (full coverage or minimal gaps) with 2-point or higher improvements from baseline (among those with baseline scores ≥2 [significant gaps to no notable hair]) were analyzed through week 76., Results: At week 52, of the 340 patients (mean [SD] age, 38.4 [12.9] years; 212 [62.4%] female) treated with baricitinib, 2 mg, 212 (62.4%) had a SALT score higher than 20 and were uptitrated to baricitinib, 4 mg. Two-thirds of these patients (142 of 212 [67.0%]) had a baseline SALT score of 95 to 100, indicating very severe AA. At week 76, 55 of the 212 patients (25.9%) had achieved a SALT score of 20 or lower. During the same period, response rates for clinician-reported outcome scores of 0 or 1 increased from 19.3% (31 of 161 patients) to 37.9% (61 of 161 patients) for eyebrows and from 24.1% (33 of 137 patients) to 40.9% (56 of 137 patients) for eyelashes., Conclusions and Relevance: In this pooled analysis of the BRAVE-AA1 and BRAVE-AA2 trials, uptitration of baricitinib, 2 mg, to baricitinib, 4 mg, in those who did not respond to the 2-mg dose resulted in meaningful improvement of response rates over the subsequent 24 weeks for scalp, eyebrow, and eyelash hair loss., Trial Registration: ClinicalTrials.gov Identifiers: NCT03570749 and NCT03899259.

Background: Few training opportunities or resources for non-expert implementers focus on the "practice" as opposed to the "science" of knowledge translation (KT). As a guide for novice implementers, we present an open-access, fillable workbook combining KT theories, models, and frameworks (TMFs) that are commonly used to support the implementation of evidence-based practices. We describe the process of creating and operationalizing our workbook., Methods: Our team has supported more than 1000 KT projects and 300 teams globally to implement evidence-based interventions. Our stakeholders have consistently highlighted their need for guidance on how to operationalize various KT TMFs to support novice implementers in "practising" KT. In direct response to these requests, we created a pragmatic, fillable KT workbook. The workbook was designed by KT scientists and experts in the fields of adult education, graphic design, and usability and was piloted with novice implementers. It is rooted in an integrated KT approach and applies an intersectionality lens, which prompts implementers to consider user needs in the design of implementation efforts., Results: The workbook is framed according to the knowledge-to-action model and operationalizes each stage of the model using appropriate theories or frameworks. This approach removes guesswork in selecting appropriate TMFs to support implementation efforts. Implementers are prompted to complete fillable worksheets that are informed by the Theoretical Domains Framework, the Consolidated Framework for Implementation Research, the Behaviour Change Wheel, the Effective Practice and Organization of Care framework, Proctor's operationalization framework, the Durlak and DuPre process indicators, and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. As they complete the worksheets, users are guided to apply theoretically rooted approaches in planning the implementation and evaluation of their evidence-based practice., Conclusions: This workbook aims to support non-expert implementers to use KT TMFs to select and operationalize implementation strategies to facilitate the implementation of evidence-based practices. It provides an accessible option for novice implementers who wish to use KT methods to guide their work., (© 2023. BioMed Central Ltd.)

Background and Objective: Data on real-world healthcare costs for ixekizumab (IXE) and secukinumab (SEC) in biologic-experienced patients with psoriasis are limited. This study compared real-world costs and healthcare resource utilization between IXE and SEC in biologic-experienced patients with psoriasis over an 18-month follow-up period in the USA., Methods: Adult patients with a diagnosis of psoriasis between 1 March, 2015 and 31 October, 2019 were identified using health insurance claims data from IBM Watson Health MarketScan ® . The index date was the date of the first IXE or SEC claim. Biologic-experienced patients with one or more pre-period claims for biologic drugs were identified. Inverse probability of treatment weighting was used to reduce cohort imbalances. All-cause and psoriasis-related direct healthcare costs along with index drug costs were estimated during the follow-up and reported as per patient per month. Discount factors published by the Institute for Clinical and Economic Review were applied to psoriasis-related biologics to adjust pharmacy costs., Results: A total of 411 IXE and 780 SEC users were included. After weighting, all-cause inpatient admissions were similar between IXE (9.5%) and SEC users (10.3%). Weighted, mean ± standard deviation per patient per month all-cause healthcare costs were higher in IXE users ($6670 ± $2910) than in SEC users ($6239 ± $3903; p = 0.049). Psoriasis-related and monthly index drug costs were higher in IXE users ($5609 ± $2009; p < 0.001 and $4688 ± $1994; p < 0.001, respectively) than in SEC users ($5095 ± $2291 and $3853 ± $1977, respectively). After Institute for Clinical and Economic Review adjustment, mean per patient per month all-cause ($4363 ± $2576 vs $4398 ± $3517) and psoriasis-related costs ($3302 ± $1264 vs $3253 ± $1504) were similar between the groups. Institute for Clinical and Economic Review- and adherence-adjusted mean per patient per month index drug costs were similar between IXE and SEC users (p = 0.339)., Conclusions: Institute for Clinical and Economic Review-adjusted all-cause and psoriasis-related costs were comparable between IXE and SEC users among biologic-experienced patients over an 18-month follow-up period., (© 2023. The Author(s).)

Purpose: Persistent fetal vasculature (PFV) may be associated with tractional retinal detachment due to tractional contraction of the fibrovascular stalk. PFV is often thought to be congenital and non-progressive. A rhegmatogenous component is far less common and is typically identified as a post-operative complication and has not been spontaneously reported. We present five cases illustrating potential progressive changes and complications that may arise in non-operated PFV., Methods: A retrospective case series of five patients who presented with progressive retinal detachments from persistent fetal vasculature., Results: Five unique cases of persistent fetal vasculature with significant progression from time of initial presentation, four of which included development of rhegmatogenous components., Conclusion: Patients with PFV and a seemingly stable tractional detachment should undergo evaluation with a retina specialist for risk stratification and management, as rhegmatogenous detachments may occur due to ocular growth and stretch breaks, and tractional detachments can continue to progress over time., Competing Interests: The authors declare no conflicts of interest. No outside funding was utilized. The authors declare no proprietary interests related to this manuscript.

Objective: The aim of this study was to compare healthcare costs between ixekizumab (IXE)-treated and secukinumab (SEC)-treated patients with psoriasis over a 24-month follow-up period in the United States., Methods: Patients with psoriasis diagnosis were identified from IBM Watson Health MarketScan ® Research Databases; those with one or more claim for index drug (IXE or SEC) between March 1, 2016 and October 31, 2019 were included. Included patients were ≥ 18 years old and had continuous enrollment with medical and pharmacy benefits ≥ 6 months before and ≥ 24 months after index date. Patients were classified as IXE or SEC users based on drug received at index. Per patient per month (PPPM) all-cause, psoriasis-related, and index drug costs for IXE and SEC users were estimated over 24 months of follow-up. Institute for Clinical and Economic Review (ICER) discount factors were applied to adjust pharmacy costs. Index drug costs were additionally adjusted for adherence. Inverse probability of treatment weighting was used to address cohort imbalances. Chi-square/t tests were used to compare IXE versus SEC users; p value < 0.05 was considered statistically significant., Results: Overall, 1461 patients (IXE users, n = 471; SEC users, n = 990) were included. IXE versus SEC users had higher weighted PPPM all-cause, psoriasis-related, and index drug costs (p ≤ 0.001). IXE versus SEC users had comparable ICER-adjusted mean PPPM all-cause costs (US$4172 ± 3349 vs US$3978 ± 2619; p = 0.227) and psoriasis-related costs (US$2950 ± 1332 vs US$2899 ± 1152; p = 0.447). After applying ICER and adherence adjustments, index drug costs were similar between IXE and SEC users (US$3794 ± 1822 vs US$3766 ± 1973; p = 0.795)., Conclusions: All-cause and psoriasis-related costs were comparable between IXE and SEC users after ICER adjustments; index drug costs were similar after ICER and adherence adjustments., (© 2022. The Author(s).)

Background: Despite the potential for ethical violations when research is conducted with conflict-affected populations, there is limited information on how and the extent to which ethical considerations specific to doing research with these populations are integrated into national and international ethics guidelines and, in turn, how these guidelines translate into practice. This study aims to fill this gap by systematically analyzing the existing research ethics guidance of humanitarian donor countries, conflict-affected countries, United Nations (UN) agencies, and funding agencies, as well as ethics reporting in research articles on conflict-affected populations published in peer-reviewed journals., Methods: A review of 32 research ethics guidelines and granting regulations from UN agencies, donor agencies, and governments was conducted, and the reporting of ethics procedures and practices of 498 articles published in peer-reviewed journals was analyzed., Results: Of the reviewed guidelines and regulations, 87.5% did not mention conflict-affected populations, and only one guideline (3.1%) catalogued any of the complexities of conducting research with conflict-affected populations. Among the reviewed published research articles on conflict-affected populations, obtaining ethics approval or a waiver was reported in only 48.2% of articles, and obtaining informed consent was reported in only 46.6% of studies. In the subset of articles that did not report receiving ethics approval, 88.5% were published in journals that required reporting of ethics approval., Conclusions: This study highlighted a gap in current research guidelines and granting regulations on the ethical conduct of research with conflict-affected populations and illustrated the need for such guidance to be integrated into governing documents and research practices. Moreover, this study demonstrated that there is a need for stricter enforcement of reporting requirements by journals to ensure that research with conflict-affected populations meets the required ethical standard. Partnerships among institutional ethics committees, donor agencies, and journals can ensure that the rights of conflict-affected populations are protected., (Copyright 2022 American Medical Association. All Rights Reserved.)

Importance: About 1% of children and adolescents worldwide are affected by plaque psoriasis., Objective: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis., Design, Setting, and Participants: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021., Interventions: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60., Main Outcomes and Measures: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation., Results: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection., Conclusions and Relevance: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT03073200.

Background: There is a paucity of long-term real-world evidence comparing the effectiveness of ixekizumab (IXE) and adalimumab (ADA). We compared real-world treatment patterns of IXE-treated and ADA-treated patients with psoriasis over 24 months in the United States., Methods: A retrospective observational study was conducted using IBM Watson Health MarketScan&reg; databases. Adult patients with psoriasis having &ge;1 claim for IXE or ADA from March 1, 2016 &ndash; October 31, 2019 were identified. Inverse probability of treatment weighting (IPTW) was used to address cohort imbalances. Cox proportional hazards models were used to estimate the risks of non-persistence, discontinuation, and switching. Logistic regression was used to estimate odds of high adherence. Persistence, adherence, discontinuation, reinitiation, and dosing and switching rates were also analyzed., Results: The final cohorts comprised 475 IXE users and 3159 ADA users over 24 months. IXE users demonstrated higher adherence (36.3% vs 28.8%; P&lt;0.001) and persistence rates (35.2% vs 28.8%; P=0.004), and a lower discontinuation rate (59.1% vs 65.3%; P=0.007) compared to ADA users. IXE users had a higher likelihood of being treatment-adherent compared to ADA users (OR=1.52, 95% CI: 1.24&ndash;1.87), a lower risk of non-persistence (HR=0.84, 95% CI: 0.75&ndash;0.95), and a lower risk of discontinuation (HR=0.83, 95% CI: 0.74&ndash;0.94), respectively. Switching rates were similar in both groups (31.2% vs 30.0%; P=0.608)., Conclusion: IXE users had better treatment adherence and persistence, and a lower risk of discontinuation compared to ADA users over 24 months. There was no difference in the risk of switching between IXE and ADA. J Drugs Dermatol. 2022;21(4):399-407. doi:10.36849/JDD.6336.

The real-world data on short course of immune checkpoint inhibitor (ICI) use are sparse and merit exploration. A multicentric observational study on the safety and efficacy of ICI in oncology patients between August 2014 and October 2020 involves 1011 patients across 13 centers in India. The median age was 59 (min 16-max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles was 5 (95% confidence interval [CI] 1-27), and the median duration of therapy was 3 (95% CI 0.5-13) months. ICIs were used commonly in the second and third line setting in our study (66.4%, n = 671). Objective response rate (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease, and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n = 906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow-up of 14.1 (95% CI 12.9-15.3) months, there were 616 events of progression and 443 events of death, and the median progression free survival and overall survival were 6.4 (95% CI 5.5-7.3) and 13.6 (95% CI 11.6-15.7) months, respectively, in the overall cohort. Among the immune-related adverse events, autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy have comparable efficacy/safety to international literature with standard ICI therapy., (© 2021 UICC.)

Introduction: Music-based interventions are used to improve well-being in individuals who are psychologically vulnerable and have long-term illnesses. To date, no study has systematically assessed the literature on music-based interventions aimed at improving well-being in people who have a vision impairment (VI). The purpose of the current protocol is to provide the methodology for a scoping review, to explore the therapeutic outcomes and strategies used in music-based interventions aimed specifically at people with a VI., Methods and Analysis: This scoping review protocol was developed according to the Joanna Briggs Institute methodology and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist and guidelines. The anticipated start date for this study was July 2021. The proposed review will include studies that use music therapeutically as part of a treatment intervention for all VI populations. Studies that meet the inclusion criteria with regards to population, concept and context will be included. Electronic database searches will be conducted independently by two researchers and include MEDLINE, EMBASE, CINAHL Plus, PsycINFO and Web of Science. Further searches will include the reference lists of included studies and grey literature. A narrative synthesis will be conducted to map out the types of therapeutic music interventions undertaken and to compare therapeutic outcomes., Ethics and Dissemination: As the methodology of this study consists of collecting data from publicly available articles, it does not require ethics approval. The findings of the planned scoping review are important to guide the development of future interventions, or strategies, that will attempt to use music to improve well-being in people with a VI. The results will be disseminated through a peer-reviewed publication and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Real-world data on long-term treatment patterns associated with interleukin-17A inhibitors in plaque psoriasis are lacking., Objective: To compare ixekizumab or secukinumab treatment patterns over a 24-month period among plaque psoriasis patients., Methods: Adult patients with psoriasis who had 1 or more claims for ixekizumab or secukinumab between March 1, 2016, and October 31, 2019, and with 24 months of follow-up after starting treatment were identified from IBM MarketScan claims databases. Inverse probability of treatment weighting and multivariable models were employed to balance cohorts and estimate the risks of nonpersistence, discontinuation, and switching and odds of highly adherent treatment (proportion of days covered ≥ 80%)., Results: A total of 471 ixekizumab and 990 secukinumab users were included. Compared to secukinumab, ixekizumab use was associated with a 20% lower risk of nonpersistence (hazard ratio, 0.80; 95% CI, 0.70-0.92), a 17% lower risk of discontinuation (hazard ratio, 0.83; 95% CI, 0.72-0.96), and a 42% higher odds of being highly adherent to treatment (odds ratio, 1.42; 95% CI, 1.12-1.80). No difference in risk of switching was observed (hazard ratio, 0.83; 95% CI, 0.68-1.01)., Limitations: Disease severity and clinical outcomes were unavailable., Conclusion: Over 24 months, ixekizumab users exhibited better persistence and adherence, and a lower risk of discontinuation than secukinumab users in real-world settings., Competing Interests: Conflicts of interest Dr Blauvelt had received honoraria as a scientific adviser/clinical study investigator from AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma, but none related to this work. Drs Shi and Lew and Author Zimmerman are employees of IBM Watson Health, which was compensated by Eli Lilly and Company for conducting this research. Drs Somani, Burge, Zhu, Atiya, and Murage, and Author Ridenour are employees of Eli Lilly and Company and hold stock in Eli Lilly and Company., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to investigate and compare the efficacy of corticosteroids, NSAIDs, and colchicine in treating postoperative pericardial effusion (PPE) following cardiac surgery in the pediatric setting, on the basis of available literature. To investigate and compare the efficacy of corticosteroids, NSAIDs, and colchicine in treating postoperative pericardial effusion (PPE) following cardiac surgery in the pediatric setting, on the basis of available literature. A systematic review was conducted by carrying out a database search in PubMed on April 20th, 2021. An English language filter was added, but no time restrictions were applied. Lack of pediatric literature prompted a broadening of the search to include adult literature. One pediatric and four adult studies were included, but the pediatric evidence was not found to be of satisfactory quality, and the findings of adult literature could not be readily generalized to the pediatric setting. No well-founded conclusions could be drawn regarding the efficacy of corticosteroids, NSAIDs, or colchicine in treating PPE, as a striking lack of evidence for their efficacy in the pediatric setting were revealed. A knowledge gap was found in the literature, indicating a need for good-quality randomized controlled trials to bridge this gap., (© 2022. The Author(s).)

Aims: To compare long-term healthcare resource utilization (HCRU) and costs among patients who initiated ixekizumab (IXE) or adalimumab (ADA) for treatment of psoriasis in the United States., Methods: Adult patients with psoriasis who had ≥1 claim for IXE or ADA were identified from IBM MarketScan claims databases prior to the COVID-19 pandemic (1 March 2016-31 October 2019). The index date was the date of first claim for the index drug of interest. Inverse probability of treatment weighting was employed to balance treatment cohorts. All-cause and psoriasis-related HCRU and costs were examined for 24 months of follow-up. Costs were reported as per patient per month. Costs of psoriasis-related biologics were adjusted using published Institute for Clinical and Economic Review (ICER) discount factors. Index drug costs were adjusted for adherence and ICER discount rates., Results: The analyses included 407 IXE and 2,702 ADA users. IXE users had significantly higher inpatient admission rate (all-cause HCRU: 14.9% vs. 11.0%; p  =0.012) and greater mean length of stay per admission (days, 6.6 vs. 4.1; p  =0.004) than ADA users. ICER-adjusted costs were significantly higher in IXE than ADA users (all-cause costs: $4,132 vs. $3,610; p  <0.001; psoriasis-related costs $3,077 vs. $2,700; p  <0.001). After adjusting for ICER and adherence, IXE and ADA drug costs were comparable ($3,636 vs. $3,677; p  =0.714)., Limitations: Study relied on administrative claims data, subjected to data coding limitations and data entry errors. Rebates, patient assistance programs, and commission to wholesalers are not always captured in claims. Adjustment made by ICER discount factors may lead to double-discounting if the discounts have been applied in claim payments., Conclusions: All-cause HCRU was higher in IXE than ADA users. Healthcare costs were also higher in IXE than ADA users after ICER adjustment, over 24 months. Cost differences were largely driven by higher treatment adherence associated with IXE. Index drug costs were comparable after ICER and adherence adjustments.

Background/objectives: Information is limited on the relationship between skin clearance, resolution of challenging body areas, and improvement of patient-reported outcomes (PROs) in pediatric psoriasis. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe psoriasis in patients aged 6 to <18 years. This study examines improvement in psoriasis clearance in challenging body areas in pediatric patients relative to health-related quality of life., Methods: Data from the IXORA-PEDS trial (NCT03073200) were analyzed, and changes from baseline were measured for overall Psoriasis Area and Severity Index (PASI), static Physicians' Global Assessment of psoriasis (sPGA), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (PPASI), and Nail Psoriasis Severity Index. Rates of Dermatology Life Quality Index (DLQI), or Children's DLQI (CDLQI), scores of 0 or 1 were evaluated using the Cochran-Armitage trend test., Results: Higher rates of DLQI/CDLQI (0,1) scores were significantly associated with greater PASI and PSSI responses at both Week 12 and Week 48 (p < .0001). A significant association was also observed between DLQI/CDLQI (0,1) and sPGA scores (p < .0001). Significantly higher rates of DLQI/CDLQI (0,1) scores were achieved in patients with greater levels of palmoplantar clearance as measured by PPASI at Week 12 (p = .0139), but significance was not sustained at Week 48 (p = .0896)., Conclusions: Greater skin clearance and scalp resolution are associated with better PROs over a short-term (12-week) and long-term (48-week) period. This demonstrates that greater improvement of skin clearance and scalp resolution may benefit quality of life in pediatric patients with psoriasis., (© 2021 Eli Lilly and Company. Pediatric Dermatology published by Wiley Periodicals LLC.)

Introduction: Real-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA., Methods: A retrospective observational study using administrative claims data from IBM ® Watson Health MarketScan ® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching., Results: Overall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05-1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68-0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68-0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60-0.93)., Conclusion: This study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment., (© 2021. The Author(s).)

In electrical discharge machining (EDM), the machined surface quality can be affected by the excessive temperature generation during the machining process. To achieve a longer life of the finished part, the machined surface quality plays a key role in maintaining its overall integrity. Surface roughness is an important quality evaluation of a material's surface that has considerable influence on mechanical performance of the material. Herein, a sintered cermet tooltip with 75% copper and 25% titanium carbide was used as tool electrode for processing H13 steel. The experiments have been performed to investigate the effects of EDM parameters on the machined surface roughness. The findings show that, as the pulse current, pulse length, and pulse interval are increased, the surface roughness tends to rise. The most significant determinant for surface roughness was found to be pulse current. A semi-empirical surface roughness model was created using the characteristics of the EDM technique. Buckingham's theorem was used to develop a semi-empirical surface roughness prediction model. The semi-empirical model's predictions were in good agreement with the experimental studies, and the built empirical model based on physical features of the cermet tooltip was tested using dimensional analysis.

Purpose: Vision impairment (VI) may impact a person's functional ability resulting in a loss of independence, anxiety, depression, social isolation and reduced quality of life. Caregivers also experience similar problems due to the increased burden placed on them. Support to address these difficulties encountered by those with VI and their caregivers may not always be accessible. An internet-based intervention may provide more accessible support. The aim of this study was to obtain consensus regarding the content and accessibility features required to design an internet-based intervention to promote wellbeing for people with VI and their caregivers., Method: A three-round Delphi review was conducted with a panel of 30 stakeholders. Three stakeholder groups were included, namely individuals with vision loss, experts in the field of vision loss and mental health and carers of individuals with vision loss. Conceptual wellbeing ideas were examined in round 1, the intervention modules and module content were proposed in round 2 and refined in round 3., Results: Consensus of 75% or more was reached to include 18 modules into the intervention. These were divided into seven sections: understanding vision loss, emotional wellbeing, functional wellbeing, social wellbeing, physical wellbeing, wellbeing for carers and maintaining wellbeing. The accessibility features deemed most important were font size, colour and contrast options, compatibility with low vision aids and layout of the intervention., Conclusions: The Delphi process positively informed the design of an internet-based intervention for individuals with acquired VI and their caregivers. Suggestions provided by stakeholders should now be incorporated into the intervention. Future evaluation of efficacy and cost-effectiveness of such an intervention are necessary., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Aim and Objective: This study aims to compare the resistance to fracture in maxillary incisors which were fractured in two different oblique patterns and then were re-attached and reinforced using anatomic fiber-reinforced composite (FRC) post., Materials and Methods: Sixty extracted and intact human maxillary incisors were obtained and divided into two groups (A and B; n = 30). "Labiopalatal" and "palatolabial" fractures were induced in group A and group B, respectively. These two groups were further subdivided into two subgroups ( n = 15). In subgroup I Ribbond fiber (Ribbond Inc., Seattle, WA, USA) and in subgroup II Everstick post (everStick Post™, GC Corporation, Tokyo, Japan) were used. Fractured fragments were re-attached using resin and tested for fracture resistance in universal testing machine. Statistical analysis was done with ANOVA one-way test and post hoc test., Results: The labiopalatal fracture pattern of group A showed significantly increased resistance to fracture than the palatolabial fracture pattern of group B in both the subgroups. Similarly, subgroup II with Everstick post exhibited significantly higher fracture resistance than subgroup I with Ribbond in both groups A and B ( p value < 0.05)., Clinical Significance: The study simulates a clinical scenario of coronal fracture of a tooth and focuses on the techniques and materials which can be used for successful management of such cases., How to Cite This Article: Khurana D, Prasad AB, Raisingani D, et al. Comparison of Ribbond and Everstick Post in Reinforcing the Re-attached Maxillary Incisors Having Two Oblique Fracture Patterns: An In Vitro Study. Int J Clin Pediatr Dent 2021;14(5):689-692., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Ti-6Al-4V is an alloy that has a high strength-to-weight ratio. It is known as an alpha-beta titanium alloy with excellent corrosion resistance. This alloy has a wide range of applications, e.g., in the aerospace and biomedical industries. Examples of alpha stabilizers are aluminum, oxygen, nitrogen, and carbon, which are added to titanium. Examples of beta stabilizers are titanium-iron, titanium-chromium, and titanium-manganese. Despite the exceptional properties, the processing of this titanium alloy is challenging when using conventional methods as it is quite a hard and tough material. Nonconventional methods are required to create intricate and complex geometries, which are difficult with the traditional methods. The present study focused on machining Ti-6Al-4V using wire electrical discharge machining (WEDM) and conducting numerous experiments to establish the machining parameters. The optimal setting of the machining parameters was predicted using a multiresponse optimization technique. Experiments were planned using the response surface methodology (RSM) technique and analysis of variance (ANOVA) was used to determine the significance and contribution of the input parameters to changes in the output characteristics (cutting speed and surface roughness). The cutting speed obtained during the processing of the annealed titanium alloy using WEDM was quite large as compared to the cutting speed obtained in the case of processing the pure, quenched, and hardened titanium alloys using WEDM. The maximum cutting speed obtained while processing the annealed titanium alloy was 1.75 mm/min.

Purpose: Limited treatment options are available for patients with advanced non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. The treatment of recurrent advanced NSCLC progressed with the arrival of nivolumab and other immunotherapeutic agents. Our single-center prospective study aimed to present the effectiveness and safety of nivolumab in second-line setting after first-line platinum doublet in Indian patients with advanced NSCLC., Patients and Methods: Twenty-nine adult patients with stage IV NSCLC treated with nivolumab after failure of first-line platinum-based chemotherapy at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, India, between October 2016 and January 2018, were included in the study. Overall survival (OS), hematological, and nonhematological toxicities were evaluated., Results: A total of 29 patients (mean age of 59.6 years at enrollment) were evaluated. Histological evaluation revealed adenocarcinoma (44.8%) and squamous (55.2%) type of cancer. The Eastern Cooperative Oncology Group performance score was II in 7 patients (24.1%) and I in 22 (75.9%) patients. Patients received an average of four cycles of nivolumab. The median survival duration was 101 days, and OS rate in the study was 51.7%. Six patients (20.7%) had stable disease response, five patients (17.2%) had partial response, and three patients (10.3%) were lost to follow-up. Asthenia and cough were the most common nonhematological toxicities. Only three patients developed hematological toxicities (anemia and thrombocytopenia)., Conclusion: Data from our study suggest nivolumab is well-tolerated and effective in Indian patients with recurrent advanced NSCLC after failure of the multiple first lines of platinum-based combination chemotherapy., Competing Interests: None

Background: Missing health care appointments without canceling in advance results in a no show, a vacant appointment slot that cannot be offered to others. No show can be reduced by reminding patients about their appointment in advance. In this regard, mobile health (mHealth) strategy is to use text messaging (short message service, SMS), which is available on all cellular phones, including cheap low-end handsets. Nonattendance for appointments in health care results in wasted resources and disturbs the planned work schedules., Objectives: The purpose of this study is to evaluate the efficacy of the current text messaging (SMS) and call-based reminder system and further explore how to improve the attendance at the pediatric outpatient clinics. The primary objectives are to (1) determine the efficacy of the current clinic appointment reminder service at pediatric outpatient clinics at Aga Khan University Hospital, (2) assess the mobile phone access and usage among caregivers visiting pediatrics consultant clinics, and (3) explore the perception and barriers of parents regarding the current clinic appointment reminder service at the pediatric outpatient clinics at Aga Khan University Hospital., Methods: The study uses a mixed-method design that consists of 3 components: (1) retrospective study (component A) which aims to determine the efficacy of text messaging (SMS) and phone call-based reminder service on patient's clinic attendance during January to June 2017 (N=58,517); (2) quantitative (component B) in which a baseline survey will be conducted to assess the mobile phone access and usage among parents/caregivers of children visiting pediatrics consultant clinics (n=300); and (3) qualitative (component C) includes in-depth interviews and focus group discussion with parents/caregivers of children visiting the pediatric consultancy clinic and with health care providers and administrative staff. Main constructs will be to explore perceptions and barriers related to existing clinic appointment reminder service. Ethics approval has been obtained from the Ethical Review Committee, Aga Khan University, Pakistan (4770-Ped-ERC-17)., Results: Results will be disseminated to pediatric quality public health and mHealth communities through scientific meetings and through publications, nationally and internationally., Conclusions: This study will provide insight regarding efficacy of using mHealth-based reminder services for patient's appointments in low- and middle-income countries setup. The finding of this study will be used to recommend further enhanced mHealth-based solutions to improve patient appointments and decrease no show., (©Sana Saeed, Noureen Somani, Fatima Sharif, Abdul Momin Kazi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.04.2018.)

Cleft palate fistula is defined as a breakdown in the primary surgical repair of the palate resulting in oronasal communication, which can create symptomatic regurgitation for fluids/solids and affect speech, manifested by airflow escape during phonation. With the reported postoperative occurrence rate of 33-37% postfistula repair, it remains a challenging problem. The primary aim of this study was to describe our experience in the management of 7 consecutive cases of recalcitrant palatal fistula, all secondary to primary cleft palate repair. Pure cancellous bone graft was harvested in a standard fashion in sufficient quantity based on size of fistula from the iliac crest and was morselized and was kept mixed with the patient's blood. After flap turnover for nasal closure, the graft was packed over the raw surface on the oral aspect and was secured by placing an oxidized regenerated cellulose sheet fixed to the surrounding mucosa. As per the Papineau technique, no oral closure was performed. Six-month follow-up showed complete epithelization of the oral raw surface in 6 of the 7 patients. In the diverse spectra of cleft surgeries, management of recalcitrant cleft palate fistula remains a surgical challenge. Repurposing Papineau's concept of open cancellous bone grafting in cleft palate fistula is a novel attempt with a sound scientific basis. In our experience, this technique has proved to be very effective in managing recalcitrant palatal fistulae.