Palo Alto Medical Foundation

No repigmentation treatments are approved for vitiligo affecting > 10% body surface area. To assess efficacy and safety of povorcitinib (oral, selective Janus kinase 1 inhibitor) in extensive nonsegmental vitiligo. This double-blinded, placebo-controlled, dose-ranging phase 2 study (NCT04818346) randomized adult patients 1:1:1:1 to once-daily povorcitinib 15, 45, or 75 mg or placebo for 24 weeks. Subsequently, patients received povorcitinib 45 mg (initially randomized to 45 mg) or 75 mg (initially randomized to placebo, 15, or 75 mg) until week 52, followed by 24-week post-treatment follow-up. Primary endpoint was percentage change from baseline in total Vitiligo Area Scoring Index (T-VASI) at week 24. Of 171 patients (mean total body surface area/T-VASI, 28.2%/25.5) randomized, 82.5% completed the 24-week treatment. At week 24, povorcitinib significantly improved T-VASI from baseline (15 mg, 19.1%; 45 mg, 17.8%; 75 mg, 15.7%) versus placebo (-2.3%; least squares mean povorcitinib vs placebo, P < .01). Continuous improvement was observed through week 52. Incidence of grade ≥ 3 treatment-emergent adverse events was similar across treatment groups, with no new safety signals. Limited demographic diversity. Povorcitinib demonstrated substantial total body and facial repigmentation in adult patients with extensive nonsegmental vitiligo and was generally well tolerated through 52 weeks of treatment.

Chronic hepatitis B (CHB) with indeterminate phase comprises a heterogeneous group of patients. We determined the prevalence of indeterminate CHB overall and characterised novel types and phase transition probabilities of novel types of indeterminate CHB. CHB patients were enrolled retrospectively from 24 centres (9 countries/regions). Indeterminate phase was defined based on the AASLD 2018 guidance. The cohort included 8375 patients with a mean age of 45.0 ± 13.7 years, 22.5% HBeAg-positive, and median ALT and HBV DNA of 30 U/L and 4.3 ± 2.2 log10IU/mL, respectively. Of the total cohort, half (47.2%) were in the indeterminate phase; and of these, the most prevalent group among HBeAg-positive patients was Type 2 (ALT 1-2 × ULN, HBV DNA≥ 20,000 IU/mL; 12.6%), while in HBeAg-negative patients it was Type 6 (ALT<ULN, HBV DNA≥ 2000 IU/mL; 30.1%). Among the 1530 indeterminate patients with long-term follow-up, the 10-year cumulative incidence of phase transition to immune tolerant, immune active and immune inactive phases were 6.5%, 32.1% and 64.3%, respectively. The majority (73.2%) of Type 2 indeterminate patients transitioned to the immune active phase, while only 16.5% of Type 8 (HBeAg-negative, ALT 1-2 × ULN, HBV DNA < 2000 IU/mL) did. Indeterminate CHB can be classified into 10 types, with the most prevalent type being those with HBeAg-negative, HBV DNA ≥ 2000 IU/mL and ALT<ULN (30.1%). The most prevalent HBeAg-positive patients with ALT 1-2 × ULN and HBV DNA ≥ 20,000 IU/mL type was also the most likely to transition to the immune-active phase (73.2% by year-10). The monitoring and management of CHB patients with the indeterminate phase should be individualised according to their types.

Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Open-label trial with 2 treatment arms. Pediatric Endocrine Clinic at Stanford. A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.

Background and Objectives: Clinical practice guidelines (CPGs) have significantly influenced medical practice worldwide. Nevertheless, the authorship of CPGs produced by several medical societies has not been representative of the field and population they address, as women and individuals from racial and ethnic minority groups have been underrepresented as authors. We hypothesized that women and individuals from minoritized racial and ethnic groups would also be underrepresented as authors of CPGs produced by the American Academy of Pediatrics (AAP). Methods: In this cross-sectional study, the gender, race, and ethnic composition of authors and subcommittee participants of AAP-produced CPGs published from January 2010 through May 2023 were analyzed and compared to the 2010 and 2021 U.S. population and 2010 and 2022 U.S. medical school pediatric faculty. Results: Women (39.7%, 127/320 of all positions, and 42.5%, 85/200 of named author positions) and women physicians (35.2%, 101/287 of all positions, and 36.4%, 64/176 of named author positions) were significantly underrepresented-while men and men physicians were significantly overrepresented-from their respective composition in the U.S. Census and pediatric faculty. Women and women physicians from all racial and ethnic groups and men and men physicians from minority racial and ethnic groups were significantly underrepresented-from their respective composition in the U.S. Census and pediatric faculty. No Black man was identified as an author. Conclusions: Medical societies that produce CPGs should be cognizant of these inequities and ensure appropriate authorship diversity.