Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.

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Objectives: Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9month period in a UK cohort. Methods: The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variablesfor vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.

Summary Background

Background The Gaucher Investigative Therapy Evaluation (GAUCHERITE) is a national clinical cohort of 250 patients aged 5–87 years with Gaucher disease - an ultra-rare genetic disorder. To inform clinical decision-making and improve pathophysiological understanding, we characterized the course of Gaucher disease and explored the influence of costly innovative medication and other interventions. Retrospective and prospective clinical, laboratory and radiological information including molecular analysis of the GBA1 gene and comprising > 2500 variables were collected systematically into a relational database with banking of collated biological samples in a central bioresource. Data for deep phenotyping and life-quality evaluation, including skeletal, visceral, haematological and neurological manifestations were recorded for a median of 17.3 years. Results At baseline, 223 of the 250 patients were classified as type 1 Gaucher disease. Intensive neurological phenotyping in a subgroup of 40 originally considered to have only systemic features, revealed neurological involvement in 18: two had Parkinson disease and 16 patients had other neuronopathic features. This revised the number affected by type 3 Gaucher disease to a total to 43. Skeletal manifestations occurred in most patients in the cohort (131 of 201 specifically reported bone pain). Symptomatic osteonecrosis and fragility fractures occurred respectively in 76 and 37 of all 250 patients and the first osseous events occurred significantly earlier in those with neuronopathic disease. Analysis of the longitudinal real-world data permitted stratification of Gaucher disease on the basis of exposure to advanced therapies and splenectomy. Splenectomy was associated with an increased hazard of fragility fractures, osteonecrosis and orthopaedic surgery; after splenectomy, there were marked gender differences in the risk of fragility fractures over time. Combined with associated surgical procedures, the skeletal manifestations represent a heavy burden of illness, especially in patients formerly unable to access disease-modifying therapies. Conclusion Gaucher disease has been explored during a period of transformation by disease-modifying interventions. With the introduction of advanced therapies, repeated longitudinal measures in this real-world cohort allowed the condition to be stratified into clear clinical endotypes. Our study reveals diverse and changing phenotypic manifestations with neurological, systemic and skeletal disease as inter-related sources of disability. Electronic Supplementary Material The online version of this article contains supplementary material, which is available to authorized users.