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To assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).

This phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 11 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.

269 patients were randomised and treated tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.

In adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.

NCT03502616.

NCT03502616.

To estimate household cost of illness (COI) for children with severe pneumonia in Bangladesh.

An incidence-based COI study was performed for one episode of childhood severe pneumonia from a household perspective. Face-to-face interviews collected data on socioeconomic, resource use and cost from caregivers. A micro-costing bottom-up approach was applied to calculate medical, non-medical and time costs. Multiple regression analysis was applied to explore the factors associated with COI. Sensitivity analysis explored the robustness of cost parameters.

Four urban and rural study sites from two districts in Bangladesh.

Children aged 2-59 months with severe pneumonia.

1472 children with severe pneumonia were enrolled between November 2015 and March 2019. The mean age of children was 12 months (SD ±10.2) and 64% were male. The mean household cost per episode was US$147 (95% CI 141.1 to 152.7). Indirect costs were the main cost drivers (65%, US$96). Household costs for the poorest income quintile were lowe household economic burden.

To analyse the impact of blood enterovirus and human parechovirus PCR (ev-PCR) testing in young infants with fever without a source (FWS).

Observational study, subanalysis of a prospective registry.

Paediatric emergency department.

Infants ≤90 days of age with FWS seen between September 2015 and August 2019 with blood ev-PCR, blood and urine cultures and urine dipstick test performed.

Prevalence of invasive bacterial infection (IBI bacterial pathogen in blood or cerebrospinal fluid) in infants with positive or negative ev-PCR test results. Secondarily, we also compared length of stay and antibiotic treatment in hospitalised infants.

Of 703 infants, 174 (24.7%) had a positive blood ev-PCR and none of them were diagnosed with an IBI (vs 2.6% (95% CI 1.3% to 4.0%) of those with a negative result, p=0.02). Prevalence of non-IBI (mainly urinary tract infection) was also lower among infants with a positive blood ev-PCR (2.3% (95% CI 0.1% to 4.5%) vs 17.6% (95% CI 14.3% to 20.8%), p<0.01).Overall, 258 infants were hospitalised (36.6%) and 193 (74.8%) of them received antibiotics. Length of hospital stay and antibiotic treatment were shorter in those with a positive blood ev-PCR (median 3 days vs 5 days and 1 day vs 5 days, respectively; p<0.01). Differences remained statistically significant among well-appearing infants >21 days old with normal urine dipstick.

Blood ev-PCR identifies a group of infants under 90 days of age with FWS at very low risk of IBI. Tamoxifen This test may help to guide clinical decision making in young febrile infants.

Blood ev-PCR identifies a group of infants under 90 days of age with FWS at very low risk of IBI. This test may help to guide clinical decision making in young febrile infants.After more than 30 years of efforts to eliminate polio, India was certified polio free by WHO in 2014. The final years prior to polio elimination were characterised by concentrated efforts to vaccinate hard-to-reach groups in the state of Uttar Pradesh, including migrant workers, religious minority Muslims and impoverished communities with poor pre-existing social support systems. This article aims to describe the management strategies employed by India to improve the deployment and acceptance of vaccines among hard-to-reach groups in Uttar Pradesh in the final years prior to polio elimination.Three main management principles contributed to polio elimination among the hardest to reach in Uttar Pradesh bundling of health services, local stakeholder engagement and accountability mechanisms for public health initiatives. In an effort to market the polio campaign as an authentic health-oriented programme, vaccine acceptance was improved by packaging other basic healthcare services such as routine check-ups and essential medications. India also prioritised local stakeholder engagement by using influential community leaders to reach vaccine hesitant groups. Lastly, the accountability mechanisms developed between non-profit organisations and decision-makers in the field ensured accurate reporting and identified deficiencies in healthcare worker training. The lessons learnt from India's polio vaccination programme have important implications for the implementation of future mass vaccination initiatives, particularly when trying to reach vulnerable communities.

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