Long-term efficacy and safety of baricitinib in patients with severe alopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2.

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.

Correction to "A Templating Approach to Controlling the Growth of Coevaporated Halide Perovskites".

[This corrects the article DOI: 10.1021/acsenergylett.3c01368.].

A Templating Approach to Controlling the Growth of Coevaporated Halide Perovskites.

Metal halide perovskite semiconductors have shown significant potential for use in photovoltaic (PV) devices. While fabrication of perovskite thin films can be achieved through a variety of techniques, thermal vapor deposition is particularly promising, allowing for high-throughput fabrication. However, the ability to control the nucleation and growth of these materials, particularly at the charge-transport layer/perovskite interface, is critical to unlocking the full potential of vapor-deposited perovskite PV. In this study, we explore the use of a templating layer to control the growth of coevaporated perovskite films and find that such templating leads to highly oriented films with identical morphology, crystal structure, and optoelectronic properties independent of the underlying layers. Solar cells incorporating templated FA0.9Cs0.1PbI3-xClx show marked improvements with steady-state power conversion efficiency over 19.8%. Our findings provide a straightforward and reproducible method of controlling the charge-transport layer/coevaporated perovskite interface, further clearing the path toward large-scale fabrication of efficient PV devices.

Incidence and prevalence of alopecia areata in the Australian primary care setting: A retrospective analysis of electronic health record data.

BACKGROUND: Alopecia areata (AA) is a common immune-mediated non-scarring hair loss, with a worldwide incidence between 0.57% and 3.8%. The incidence and prevalence of AA in the Australian general population have not been previously reported. OBJECTIVE: To describe the incidence and prevalence of AA in Australia using primary care data. A secondary objective was to identify common demographic characteristics, comorbidities and treatment patterns among Australians living with AA. METHODS: We analysed electronic health record data captured from a national clinical practice management software over a 10-year index period between 2011 and 2020 calendar years, inclusive. The incidence of new-onset AA and the prevalence of active records with AA were estimated. Differences in incidence by sociodemographic groups, and patterns of treatment were also evaluated. RESULTS: There were 976 incident AA records. The incidence of new-onset AA in the total study cohort was 0.278 per 1000 person-years (95% CI 0.26-0.295). By age, the incidence was highest in the 19- to 34-year-old age bracket (0.503 per 1000 person-years: 95% CI 0.453-0.554). AA incidence was lower among females than males (IRR 0.763, p < 0.001, 95% CI 0.673-0.865). Among active records, 520 were prevalent AA records. AA point prevalence at 31/12/2020 was 0.13% (1.26 per 1000 persons; 95% CI 1.15-1.37). CONCLUSION: This is the first study to describe the epidemiology (incidence and point prevalence) and management of AA in the Australian primary health-care population through large-scale database analysis. Incidence and prevalence findings were consistent with earlier estimates from other regions.

Overcoming Nanoscale Inhomogeneities in Thin-Film Perovskites via Exceptional Post-annealing Grain Growth for Enhanced Photodetection.

Antisolvent-assisted spin coating has been widely used for fabricating metal halide perovskite films with smooth and compact morphology. However, localized nanoscale inhomogeneities exist in these films owing to rapid crystallization, undermining their overall optoelectronic performance. Here, we show that by relaxing the requirement for film smoothness, outstanding film quality can be obtained simply through a post-annealing grain growth process without passivation agents. The morphological changes, driven by a vaporized methylammonium chloride (MACl)-dimethylformamide (DMF) solution, lead to comprehensive defect elimination. Our nanoscale characterization visualizes the local defective clusters in the as-deposited film and their elimination following treatment, which couples with the observation of emissive grain boundaries and excellent inter- and intragrain optoelectronic uniformity in the polycrystalline film. Overcoming these performance-limiting inhomogeneities results in the enhancement of the photoresponse to low-light (<0.1 mW cm-2) illumination by up to 40-fold, yielding high-performance photodiodes with superior low-light detection.

Athena: Speciality Certificate Examination case for Paediatrics and Genetics: a case of brittle hair.

Genetic hair disorders can be an isolated phenomenon or part of a multisystem syndrome. Microscopic examination of scalp hair can provide useful information to aid diagnosis. This article describes several hair-shaft abnormalities, outlines genetic hair disorders with their associated genetic mutations, and clinical/hair phenotypes.

Clinicopathological characteristics and treatment outcomes of fibrosing alopecia in a pattern distribution: A retrospective cohort study.

BACKGROUND: Fibrosing alopecia in a pattern distribution (FAPD) is a primary cicatricial alopecia considered a subtype of lichen planopilaris (LPP). OBJECTIVE: The clinical and histopathological features, and treatment response of 24 female patients with FAPD were evaluated. METHODS: Demographic, clinical, histopathological and treatment data of patients with FAPD were retrospectively collected. RESULTS: Twenty-four women were included (mean age 60.7 years). The mean Lichen Planopilaris Activity Index score was 1.50, and the median Sinclair grade was 3. Twelve patients had diffuse alopecia in the centroparietal region, four had frontal accentuation and eight had vertex accentuation of hair loss. Eight had associated loss of facial hair. Predominant trichoscopic features included hair shaft diameter variability (100%), perifollicular erythema and/or scaling (95%) and loss of follicular ostia (95%). Histopathological examination revealed features of scarring alopecia with interface changes in follicular epithelia mainly targeting terminal and intermediate hairs, and less frequently, vellus hairs. Treatment with hair growth-promoting, anti-inflammatory and anti-androgen agents arrested disease progression in 14 patients and resulted in hair regrowth in two patients. Six patients had progression of their hair loss in spite of treatment. LIMITATIONS: Referral bias to a specialist hair clinic, retrospective design and small sample size. CONCLUSIONS: We present clinicopathological features of FAPD which can aid in the diagnosis of this insidious scarring alopecia. Our findings suggest a more favourable outcome if treatment is initiated in early stages of the disease.

Determining Out-of-Plane Hole Mobility in CuSCN via the Time-of-Flight Technique To Elucidate Its Function in Perovskite Solar Cells.

Copper(I) thiocyanate (CuSCN) is a stable, low-cost, solution-processable p-type inorganic semiconductor used in numerous optoelectronic applications. Here, for the first time, we employ the time-of-flight (ToF) technique to measure the out-of-plane hole mobility of CuSCN films, enabled by the deposition of 4 µm-thick films using aerosol-assisted chemical vapor deposition (AACVD). A hole mobility of ∼10-3 cm2/V s was measured with a weak electric field dependence of 0.005 cm/V1/2. Additionally, by measuring several 1.5 µm CuSCN films, we show that the mobility is independent of thickness. To further validate the suitability of our AACVD-prepared 1.5 µm-thick CuSCN film in device applications, we demonstrate its incorporation as a hole transport layer (HTL) in methylammonium lead iodide (MAPbI3) perovskite solar cells (PSCs). Our AACVD films result in devices with measured power conversion efficiencies of 10.4%, which compares favorably with devices prepared using spin-coated CuSCN HTLs (12.6%), despite the AACVD HTLs being an order of magnitude thicker than their spin-coated analogues. Improved reproducibility and decreased hysteresis were observed, owing to a combination of excellent film quality, high charge-carrier mobility, and favorable interface energetics. In addition to providing a fundamental insight into charge-carrier mobility in CuSCN, our work highlights the AACVD methodology as a scalable, versatile tool suitable for film deposition for use in optoelectronic devices.

Emergency Laparotomy Follow-Up Study (ELFUS): prospective feasibility investigation into postoperative complications and quality of life using patient-reported outcome measures up to a year after emergency laparotomy.

BACKGROUND: Emergency laparotomy carries a significant risk profile around the time of surgery. This research aimed to establish the feasibility of recruitment to a study using validated scoring tools to assess complications after surgery; and patient-reported outcome measures (PROMs) to assess quality of life and quality of recovery up to a year following emergency laparotomy (EL). METHODS: We used our local National Emergency Laparotomy Audit (NELA) register to identify potential participants at a single NHS centre in England. Complications were assessed at 5, 10 and 30 days after EL. Patient-reported outcome measures were collected at 1, 3, 6 and 12 months after surgery using EQ5D and WHODAS 2.0 questionnaires. RESULTS: Seventy of 129 consecutive patients (54%) agreed to take part in the study. Post-operative morbidity survey data was recorded from 63 and 37 patients at postoperative day 5 and day 10. Accordion Complication Severity Grading data was obtained from 70 patients. Patient-reported outcome measures were obtained from patients at baseline and 1, 3, 6 and 12 months after surgery from 70, 59, 51, 48, to 42 patients (100%, 87%, 77%, 75% and 69% of survivors), respectively. CONCLUSIONS: This study affirms the feasibility of collecting PROMs and morbidity data successfully at various time points following emergency laparotomy, and is the first longitudinal study to describe quality of life up to a year after surgery. This finding is important in the design of a larger observational study into quality of life and recovery after EL.

Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Dual Orbital Degeneracy Lifting in a Strongly Correlated Electron System.

The local structure of NaTiSi_{2}O_{6} is examined across its Ti-dimerization orbital-assisted Peierls transition at 210 K. An atomic pair distribution function approach evidences local symmetry breaking preexisting far above the transition. The analysis unravels that, on warming, the dimers evolve into a short range orbital degeneracy lifted (ODL) state of dual orbital character, persisting up to at least 490 K. The ODL state is correlated over the length scale spanning ∼6 sites of the Ti zigzag chains. Results imply that the ODL phenomenology extends to strongly correlated electron systems.

Proof of concept for the clinical effects of oral rilzabrutinib, the first Bruton tyrosine kinase inhibitor for pemphigus vulgaris: the phase II BELIEVE study.

BACKGROUND: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in the pathophysiology of pemphigus, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus. OBJECTIVES: To evaluate the efficacy and safety of oral rilzabrutinib in patients with pemphigus vulgaris in a multicentre, proof-of-concept, phase II trial. METHODS: Patients with Pemphigus Disease Area Index severity scores 8-45 received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12 weeks of follow-up. Patients initially received between 0 and ≤ 0·5 mg kg-1 prednisone-equivalent corticosteroid (CS; i.e. 'low dose'), tapered after control of disease activity (CDA; no new lesions, existing lesions healing). The primary endpoints were CDA within 4 weeks on zero-to-low-dose CS and safety. RESULTS: In total, 27 patients with pemphigus vulgaris were included: nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate disease (41%) and 16 moderate to severe (59%). The primary endpoint, CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71): 11 using low-dose CS and three using no CS. Over 12 weeks of treatment, mean CS doses reduced from 20·0 to 11·8 mg per day for newly diagnosed patients and from 10·3 to 7·8 mg per day for relapsing patients. Six patients (22%) achieved complete response by week 24, including four (15%) by week 12. Treatment-related adverse events were mostly mild (grade 1 or 2); one patient experienced grade 3 cellulitis. CONCLUSIONS: Rilzabrutinib alone, or with much lower CS doses than usual, was safe, with rapid clinical activity in pemphigus vulgaris. These data suggest that BTK inhibition may be a promising treatment strategy and support further investigation of rilzabrutinib for the treatment of pemphigus.