Estimating meaningful change thresholds for Skin Pain-Numeric Rating Scale, Sleep-Numeric Rating Scale and Dermatology Life Quality Index in patients with prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is characterized by intensely itchy nodules/lesions and skin pain, which can have a substantial impact on health-related quality of life (HRQoL). Treatment benefits on such symptoms and impacts are best assessed in trials using patient-reported outcome (PROs) instruments such as Skin Pain Numerical Rating Scale (NRS), Sleep-NRS and Dermatology Life Quality Index (DLQI). However, no guidance exists for interpreting meaningful changes in scores using these PROs in patients with PN. OBJECTIVES: The main objective was to derive within-patient (responder definition) and between-group improvement thresholds for interpreting Skin Pain-NRS, Sleep-NRS and DLQI total scores in patients with PN. The measurement properties of the three PROs were also evaluated. METHODS: Intention-to-treat (ITT), blinded and pooled data were used from the Phase 3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN. Anchor- and distribution-based methods were applied to derive responder definition and between-group thresholds for Skin Pain-NRS, Sleep-NRS and DLQI. Data were additionally used to examine the instrument measurement properties, including reliability, validity and responsiveness. RESULTS: A total of 311 patients (mean age 49.5 years, 65.3% female) were included in the pooled ITT population. The within-patient improvement threshold for Skin Pain-NRS was estimated as 4.0 points, 2.0 points for Sleep-NRS and 9.0 points for DLQI total score. A 1.5-point improvement in Skin Pain-NRS scores, 1.0-point in Sleep-NRS and 4.0-point in DLQI indicated a between-group meaningful change. Adequate to good psychometric properties were demonstrated for all three instruments. CONCLUSIONS: The results of this study can aid interpretation of Skin Pain-NRS, Sleep-NRS and DLQI scores in patients with PN in both clinical trials and clinical practice to better understand and treat PN-related skin pain and the impact of PN on sleep quality and HRQoL.

A comparative evaluation of fluoride release and rechargeability in conventional GIC (type II), pediatric GIC (type IX), and Cention-N: an in vitro study.

PURPOSE: A comparative evaluation of fluoride release and re-chargeability in conventional glass ionomer cement (GIC) (type II), Pediatric GIC (type IX), and Cention-N-an in vitro study at an interval of first, fourteenth, and twenty first days. METHODS: Three groups of test materials, each with twenty samples, were prepared. Measurements of the cumulative fluoride release [parts per million (ppm)] and re-release measured on the first, fourteenth, and twenty first days. Analysis of variance (ANOVA) was used to compare the means for different readings, and Tukey's post hoc analysis was used to compare each group with each other. RESULTS: Initial and subsequent fluoride release of Cention-N at days one, fourteen, and twenty-one were all noticeably higher than those of conventional and pediatric GIC. CONCLUSION: Compared to the Conventional and Pediatric GIC restorative materials, Cention-N was more effective in the initial and fluoride re-release.

Googling "Anatomy dissection": Pre-pandemic, pandemic, and current scenario.

OBJECTIVES: The present study was proposed to assess if the online search behavior for Anatomy dissection was affected by actual dissection being performed in the labs. The interest in dissection was ascertained and compared between pre-pandemic, pandemic, and current times. METHODS: Online web search behavior for key terms related to "Anatomy dissection" was noticed worldwide using Google Trends Tool. Relative search volume (RSV) was downloaded for these keywords worldwide using all categories, and web search settings during a period from January 1, 2018, to July 31, 2022. RESULTS: There was almost a similar google trend for the first three months in years 2018 and 2020, with a slightly lower RSV in March and a noticeable RSV decrease from April onwards in 2020. During the pre-pandemic period, the peak for RSV in the month of May was noticed. These peaks were missing in 2020 and 2021. In May 2022, RSV again increased. The top five countries with the highest search hit for "Anatomy Dissection" web were the Philippines, the United States, Canada, Australia, and India. CONCLUSIONS: There was lower search trend for "Anatomy dissection" during the pandemic period as compared to pre-pandemic period. The search trends may be associated with the closure of dissection labs and it may be concluded that Anatomy learners search for this term more often, if they are actually performing the dissections. The future integrated multi-country data and analysis from different set-ups about their ways of dissection and labs before and after the pandemic may further clarify.

The effectiveness of prenatal and postnatal home visits by paramedical professionals and women's group meetings in improving maternal and child health outcomes in low and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of prenatal and postnatal home visits (HVs) and women group meetings (WGMs) by paramedical professionals to improve maternal and child health outcomes in low- and middle-income countries (LMICs). STUDY DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic review of trials published till December 2020, as per registered protocol in The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42018091968). Outcomes were neonatal mortality rate (NMR), maternal mortality ratio (MMR), the incidence of low birth weight, and still birth rate (SBR). The Cochrane Pregnancy and Childbirth Group's Trials Register, Cochrane Central Register of Controlled Trials, PubMed, and Excerpta Medica Database (EMBASE) were searched. Pooled results were estimated using random-effects meta-analysis in RevMan version 5.2. RESULTS: Twenty-five trials met the inclusion criteria. HVs were the key intervention in 12, WGMs in 11, and both interventions in 2 trials. The pooled estimates have shown that NMR was significantly reduced by HVs (OR 0.77, confidence interval [CI]: 0.67-0.90, P = 0.0007, I2 = 77%) and WGMs (OR 0.76, CI: 0.65-0.90, P = 0.001, I2 = 71%). SBR was significantly reduced by HVs (OR 0.77, CI: 0.70-0.85; P < 0.001, I2 = 0%). Subgroup analysis of studies in which more than 10% of pregnant women participated in the WGMs showed significant reduction in NMR (OR 0.67, CI 0.58-0.77, P = 0.00001, I2 = 31%) and MMR (OR 0.55, CI 0.36-0.84, P = 0.005, I2 = 27%). Two studies reported improvement in birth weight by HVs. CONCLUSIONS: HVs and WGMs (with >10% pregnant women) by paramedical professionals are effective strategies in reducing the NMR and MMR in LMICs. HVs were also effective in reducing SBR.

Prevalence and determinants of sexual abuse among adolescent girls during the COVID-19 lockdown and school closures in Ghana: A mixed method study.

BACKGROUND: In the wake of the COVID-19 pandemic, concerns have been raised that the pandemic may derail global efforts against child sexual abuse (CSA). OBJECTIVES: This study examines the prevalence and associated factors of sexual abuse among adolescent girls in the context of the COVID-19 pandemic in Ghana. PARTICIPANTS AND SETTING: The sample comprised 853 adolescent girls aged 13-19 (16.03 ± 2.04 years) in Ghana. METHODS: The study employed a concurrent mixed-method design. RESULTS: Overall, the prevalence of CSA during the COVID-19 lockdown and school closures was 32.5 %. Protective factors for CSA were feeling safe in neighbourhood (AOR = 0.526, 95 % CI = [0.325, 0.850]) and parents often listen to opinions (AOR = 0.446, 95 % CI = [0.241, 0.826]). Risk factors for CSA were physical activity (AOR = 1.649, OR = 1.783, 95 % CIAOR = [1.093, 2.487, 95 % CIOR = [1.241, 2.561]), parents sometimes listen to opinions (AOR = 1.199, OR = 1.924, 95 % CIAOR = [0.504, 2.853], 95 % CIOR = [1.034, 3.582]), living with another relative (AOR = 2.352, OR = 2.484, 95 % CIAOR = [0.270, 20.523], 95 % CIOR = [0.317, 19.475]), Akan ethnicity (AOR = 1.576, OR = 1.437, 95 % CIAOR = [0.307, 8.091], 95 % CIOR = [0.316, 6.534]), having no disability (AOR = 1.099, OR = 1.138, 95 % CIAOR = [0.679, 1.581], 95 % CIOR = [0.786, 1.649]) and having a close relationship with parents (AOR = 1.334, OR = 1.752, 95 % CIAOR = [0.746, 2.385], 95 % CIOR = [1.096, 2.802]). CONCLUSION: Knowledge of the risk and protective factors identified in this study can guide and inform the development of CSA prevention programmes during disruptive occurrences like school closures and lockdown.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Longstanding hypersensitivity pneumonitis and its response to roflumilast: A review of its likely immunological effects.

We describe the case of a 42yr old man with evidence of hypersensitivity pneumonitis referred with cough and breathlessness for several years which had further deteriorated in the prior 12 months. He had known atopic asthma without evidence of activation. A chest CT scan showed widespread ground glass change in his lung fields. He had feather bedding at home and in his youth cleaned aviaries. His forced vital capacity and lung volumes were reduced along with oxygen saturations at rest (92% on air), overnight (83% on air) and upon walking (78%). Steroids were commenced for a total of 6 months with little consistent improvement in symptoms or objective measures and with no change in his CT scan appearance. As a result, a trial of roflumilast (a phosphodiesterase-4 inhibitor) was commenced due to its range of immunological effects and in order to avoid long-term immune suppression with mycophenolate motefil in a young patient. On roflumilast treatment his cough and breathlessness improved at 4 weeks and the chest crackles cleared. An interval Chest CT scan showed resolution of the ground glass change with improved CT scores that are maintained 2 yrs. All oxygen measures improved and nocturnal oxygen was discontinued. His Lung function has remained largely stable on roflumilast and symptoms of cough and breathlessness have resolved. This case report reviews the immunology of hypersensitivity pneumonitis and the likely actions of Roflumilast relevant to this condition. It is the first published case report documenting its use in hypersensitivity pneumonitis.

Adjustment of publication bias using a cumulative meta-analytic framework.

OBJECTIVES: Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. METHODS: The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. RESULTS: Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. CONCLUSIONS: Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.

The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75-55·97; P < 0·001) and had ≥ 3-point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26-55·34; P < 0·001) and ≥ 4-point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69-45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment-emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. CONCLUSIONS: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.

Does closed treatment of paediatric mandibular condyle fractures result in restitutional remodelling?

The treatment of paediatric mandibular condylar fracture (PMCF) is typically non-operative. The purpose of this study was to determine if non-operative management of PMCF results in a new condylar process of normal morphology to regenerate after closed treatment (restitutional remodelling). The specific aim of the study was to observe restitutional remodelling (RM) in PMCF and review the literature. The investigators designed and implemented a retrospective study on paediatric patients (age<12) with unilateral or bilateral condyle fractures treated with non-operative treatment between January 2005 and July 2015. Patients with complete records and at least 1-year follow-up were included in the study. Primary outcome variable was RM and secondary outcome variables were occlusion, maximal incisal opening (MIO), displacement, infection, facial asymmetry, and signs of temporomandibular joint ankylosis (TMJA). The study evaluated 41 patients {n=57 PMCF, (m:f-35:6)} of unilateral (n=25) and bilateral (n=16) PMCF. Fractured condyles remodelled to normal morphology in all the cases at follow-up. The Wilcoxon test revealed a statistically significant difference in MIO from the preoperative value to postoperative (p=0.001). Occlusion (except 1) was satisfactory in all cases, at follow-up with no gross facial asymmetry. There was no sign of infection at the surgical site (anterior mandible). None of the patients showed signs of TMJA at follow-up. The result of the present study demonstrates that RM of condylar fracture occurs with non-operative management. Non-operative management should be the point of care in PMCF, owing to the rapid RM, bone regeneration, and satisfactory outcome. Review of the literature also supports closed treatment.

Verification and Validation of Digital Pathology (Whole Slide Imaging) for Primary Histopathological Diagnosis: All Wales Experience.

AIMS: The study is aimed to verify Aperio AT2 scanner for reporting on the digital pathology platform (DP) and to validate the cohort of pathologists in the interpretation of DP for routine diagnostic histopathological services in Wales, United Kingdom. MATERIALS METHODS AND RESULTS: This was a large multicenter study involving seven hospitals across Wales and unique with 22 (largest number) pathologists participating. 7491 slides from 3001 cases were scanned on Leica Aperio AT2 scanner and reported on digital workstations with Leica software of e-slide manager. A senior pathology fellow compared DP reports with authorized reports on glass slide (GS). A panel of expert pathologists reviewed the discrepant cases under multiheader microscope to establish ground truth. 2745 out of 3001 (91%) cases showed complete concordance between DP and GS reports. Two hundred and fifty-six cases showed discrepancies in diagnosis, of which 170 (5.6%) were deemed of no clinical significance by the review panel. There were 86 (2.9%) clinically significant discrepancies in the diagnosis between DP and GS. The concordance was raised to 97.1% after discounting clinically insignificant discrepancies. Ground truth lay with DP in 28 out of 86 clinically significant discrepancies and with GS in 58 cases. Sensitivity of DP was 98.07% (confidence interval [CI] 97.57-98.56%); for GS was 99.07% (CI 98.72-99.41%). CONCLUSIONS: We concluded that Leica Aperio AT2 scanner produces adequate quality of images for routine histopathologic diagnosis. Pathologists were able to diagnose in DP with good concordance as with GS. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths of this study - This was a prospective blind study. Different pathologists reported digital and glass arms at different times giving an ambience of real-time reporting. There was standardized use of software and hardware across Wales. A strong managerial support from efficiency through the technology group was a key factor for the implementation of the study. LIMITATIONS: This study did not include Cytopathology and in situ hybridization slides. Difficulty in achieving surgical pathology practise standardization across the whole country contributed to intra-observer variations.

Pro-poor policies and improvements in maternal health outcomes in India.

BACKGROUND: Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997-2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India. METHODS: This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015-16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India. RESULTS: On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors. CONCLUSIONS: The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India's impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.

A phase 2, open-label study of single-dose dupilumab in children aged 6 months to <6 years with severe uncontrolled atopic dermatitis: pharmacokinetics, safety and efficacy.

BACKGROUND: Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6-17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk-benefit profile in younger children remains a significant unmet need. OBJECTIVES: To determine the pharmacokinetics, safety and efficacy of single-dose dupilumab in children with severe AD aged ≥6 months to <6 years. METHODS: This open-label, multicenter, phase 2, sequential, two-age cohort, two-dose level study (LIBERTY AD PRE-SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4-week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low-to-medium potency topical corticosteroids was allowed. RESULTS: Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose-proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by -44.6% and -49.7% (older cohort) and -42.7% and -38.8% (younger cohort), and mean Peak Pruritus NRS scores by -22.9% and -44.7% (older cohort) and -11.1% and -18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children. CONCLUSIONS: Single-dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non-linear, consistent with previous studies in adults and adolescents.

Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study.

BACKGROUND: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking. OBJECTIVES: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. METHODS: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg-1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg-1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score. RESULTS: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg-1 , 61-77 mg L-1 ; 4 mg kg-1 , 143-181 mg L-1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg-1 , 47%; 4 mg kg-1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively. CONCLUSIONS: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD.

Cadaverless anatomy: Darkness in the times of pandemic Covid-19.

The pandemic Covid-19 is responsible for a major education crisis globally and has a drastic impact on medical training as well. The objective of the present study was to envision the present and future impact of Covid-19 on anatomy learning and research. The virtual education is the only mode of teaching in current scenario. Every anatomist is unlocking technology to deliver best education however understanding of the subject without dissections or other practical teaching aids like bones, specimens, embryology models, microscopic slides etc. is challenging. This approach misses the feel and human visual impacts. Potential educational disruption is felt currently and will be experienced even after the pandemic is over due to scarcity of cadavers. As the body donor may be carrier or died of Covid-19 and there is no proven screening to rule out this infection in donor, so the acceptance of body donations is not advisable for the safety of medical students and health care workers. To conclude, anatomy education is cadaverless currently due to Covid-19 lockdown and it is prophesied that after the pandemic, real cadavers will be replaced by virtual cadavers because of paucity of cadavers. Research in the field of anatomy will also be adversely affected.

Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension.

BACKGROUND: Dupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428). OBJECTIVES: To characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents. METHODS: This was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg-1 or 4 mg kg-1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg-1 or 4 mg kg-1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). RESULTS: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L-1 and 161 ± 60 mg L-1 for 2 mg kg-1 and 4 mg kg-1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg-1 ], 47% [4 mg kg-1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg-1 ) and -51% ± 29% (4 mg kg-1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg-1 ) and -84% ± 20% (4 mg kg-1 )]. CONCLUSIONS: In adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and efficacy data support long-term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate-to-severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options. Dupilumab (monoclonal antibody against interleukin-4 receptor α) is approved for the treatment of adolescents with moderate-to-severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union). A 16-week, randomized, placebo-controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long-term safety and efficacy of dupilumab in adolescents with moderate-to-severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16-week dupilumab phase III trial. The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16-week phase III monotherapy trial.

Extent of Surgical Resection in Lower-Grade Gliomas: Differential Impact Based on Molecular Subtype.

BACKGROUND AND PURPOSE: Diffuse lower-grade gliomas are classified into prognostically meaningful molecular subtypes. We aimed to determine the impact of surgical resection on overall survival in lower-grade glioma molecular subtypes. MATERIALS AND METHODS: For 172 patients with lower-grade gliomas (World Health Organization grade II or III), pre- and postsurgical glioma volumes were determined using a semiautomated segmentation software based on FLAIR or T2-weighted MR imaging sequences. The association of pre- and postsurgical glioma volume and the percentage of glioma resection with overall survival was determined for the entire cohort and separately for lower-grade glioma molecular subtypes based on isocitrate dehydrogenase (IDH) and 1p/19q status, after adjustment for age, sex, World Health Organization grade, chemotherapy administration, and radiation therapy administration. RESULTS: For the entire cohort, postsurgical glioma volume (hazard ratio, 1.80; 95% CI, 1.18-2.75; P = .006) and the percentage of resection (hazard ratio, 3.22; 95% CI, 1.79-5.82; P < .001) were associated with overall survival. For IDH-mutant 1p/19q-codeleted oligodendrogliomas, the percentage of resection (hazard ratio, 6.69; 95% CI, 1.57-28.46; P = .01) was associated with overall survival. For IDH-mutant 1p/19q-noncodeleted astrocytomas, presurgical glioma volume (hazard ratio, 3.20; 95% CI, 1.22-8.39; P = .018), postsurgical glioma volume (hazard ratio, 2.33; 95% CI, 1.32-4.12; P = .004), and percentage of resection (hazard ratio, 4.34; 95% CI, 1.74-10.81; P = .002) were associated with overall survival. For IDH-wild-type lower-grade gliomas, pre-/postsurgical glioma volume and percentage of resection were not associated with overall survival. CONCLUSIONS: The extent of surgical resection has a differential survival impact in patients with lower-grade gliomas based on their molecular subtype. IDH-mutant lower-grade gliomas benefit from a greater extent of surgical resection, with the strongest impact observed for IDH-mutant 1p/19q-noncodeleted astrocytomas.