METHODS: This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare.

FINDINGS: From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 [64%] of 123) or White (44 [36%]). Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR]=0·16, 95% CI 0·05-0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14-0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21-1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation.

INTERPRETATION: High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life.

OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.

METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.

RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.

OBJECTIVES: To assess the effectiveness of influenza vaccine in reducing the occurrence of acute otitis media in infants and children.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, LILACS, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov (15 February 2017). We also searched the reference lists of included studies to identify any additional trials.

SELECTION CRITERIA: Randomised controlled trials comparing influenza vaccine with placebo or no treatment in infants and children aged younger than six years. We included children of either sex and of any ethnicity, with or without a history of recurrent AOM.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, assessed trial quality, and extracted data. We performed statistical analyses using the random-effects and fixed-effect models and expressed the results as risk ratio (RR), risk difference (RD), and number needed to treat for an additional beneficial outcome (NNTB) for dichotomous outcomes, with 95% confidence intervals (CI).

MAIN RESULTS: We included 11 trials (6 trials in high-income countries and 5 multicentre trials in high-, middle-, and low-income countries) involving 17,123 children aged 6 months to 6 years. Eight trials recruited participants from a healthcare setting. Ten trials (and all four trials that contributed to the primary outcome) declared funding from vaccine manufacturers. Four trials reported adequate allocation concealment, and 10 trials reported adequate blinding of participants and personnel. Attrition was low for eight trials included in the analysis.The primary outcome showed a small reduction in at least one episode of AOM over at least six months of follow-up (4 trials, 3134 children; RR 0.84, 95% CI 0.69 to 1.02; RD -0.04, 95% CI -0.08 to -0.00; NNTB 25, 95% CI 12.5 to 100; low-quality evidence).The subgroup analyses (i.e. number of courses and types of vaccine administered) showed no differences.There was a reduction in the use of antibiotics in vaccinated children (2 trials, 1223 children; RR 0.70, 95% CI 0.59 to 0.83; RD -0.11, 95% CI -0.16 to -0.06; moderate-quality evidence).We were unable to demonstrate whether there was any difference in the utilisation of health care. The use of influenza vaccine resulted in a significant increase in fever (7 trials, 10,615 children; RR 1.15, 95% CI 1.06 to 1.24; RD 0.02, 95% CI 0.00 to 0.04; low-quality evidence), rhinorrhoea (6 trials, 10,563 children; RR 1.17, 95% CI 1.07 to 1.29; RD 0.09, 95% CI 0.01 to 0.16; low-quality evidence), but no difference in pharyngitis. No major adverse events were reported.Differing from the protocol, the original publication of the review included a subgroup analysis of AOM episodes by season, and the secondary outcome 'types of influenza vaccine' was changed to a subgroup analysis. For this update, we removed the subgroup analyses for trial setting, season, and utilisation of health care due to the small number of trials involved. We removed Belshe 2000 from primary and secondary outcomes (courses of vaccine and types of vaccine) because it reported episodes of AOM per person. We did not perform a subgroup analysis by type of adverse event. We have reported each type of adverse event as a separate analysis.

Methods: This retrospective study involved 215 children aged 12 years and below with the initial diagnosis of AA and PA. Clinical factors studied were demographics, presenting symptoms, body temperature on admission (BTOA), white cell count (WCC), absolute neutrophil count (ANC), platelet count and urinalysis. Simple and multiple logistic regressions were used to determine the odds ratio of the statistically significant clinical factors. Results: The mean age of the included children was 7.98 ± 2.37 years. The odds of AA increased by 2.177 times when the age was ≥ 8 years (P = 0.022), 2.380 times when duration of symptoms ≥ 2 days (P = 0.011), 2.447 times with right iliac fossa (RIF) pain (P = 0.007), 2.268 times when BTOA ≥ 38 °C (P = 0.020) and 2.382 times when neutrophil percentage was ≥ 76% (P = 0.045). It decreased by 0.409 times with non-RIF pain (P = 0.007). The odds of PA was increased by 4.672 times when duration of symptoms ≥ 2 days (P = 0.005), 3.611 times when BTOA ≥ 38 °C (P = 0.015) and 3.678 times when neutrophil percentage ≥ 76% (P = 0.016). There was no significant correlation between WCC and ANC with AA and PA.