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Aim The aim of the study was to reach consensus on modifiable risk factors for a novel system of care to address Manifestations of Frailty in hospitalized older adults. Design Consensus study. Method A modified nominal group technique, incorporating expert group face‐to‐face interaction, review of existing evidence and pre/post‐meeting questionnaire completion was undertaken November 2019–February 2020. Results Seventy‐one risk factors, within seven risk factor domains (pain, medication, fluid and nutrition intake, mobility, elimination, infection, additional patient factors) were considered. It was agreed that 44 risk factors incorporating patient, organizational and environmental risk factors were modifiable and should be included in a novel system of care.

The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer–BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18–60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR–9nn3scw. Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8–30·1) in adults aged 18–60 years and 8·9% (4·2–16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67–88) for Ad26.COV2-S, 152 (134–173) for BNT162b2, 90 (77–104) for ChAdOx1 nCoV-19, and 12 (11–14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8–7·7) for Ad26.COV2-S, 13·4 (11·6–15·3) for BNT162b2, and 7·0 (6·1–8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9–12·9) for Ad26.COV2-S vaccine, 21·5 (14·5–31·9) for BNT162b2, and 10·6 (7·2–15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. Ministry of Health, Brazil.

The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12–18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2–10 years (PfPR2–10) and ranges from 3% to 65% PfPR2–10. Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815–333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868–405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4–48) in perennial settings and $6 (3–63) in seasonal settings and the incremental cost per DALY averted was $34 (29–139) in perennial settings and $30 (22–172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2–10. Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Paediatric COVID-19 vaccination programmes were initiated in response to the coronavirus pandemic declared by the World Health Organisation (WHO) in 2020. Ten COVID-19 vaccines received WHO Emergency Use Listing, however, only five were approved for use in children. ChAdOx1 nCoV-19 (AZD1222) was approved in adults in a two-dose regimen. We previously reported interim findings of a phase 2 study of ChAdOx1 nCoV-19 in children with immunogenicity, comparable with adults. Final results after 12 month follow-up are reported. Single-blind, randomised controlled trial across four UK centres, recruiting 261 children and adolescents (aged 6-17 years). Participants received either two doses of ChAdOx1 nCoV-19 or Bexsero vaccine (controls). The primary outcome was safety (adverse events for 28 days following vaccination and serious adverse events throughout), and secondary outcome was immunogenicity (measured by SARS-CoV-2 anti-spike enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISpot)). Five serious adverse events and four adverse events of special interest were reported. None were related to study vaccinations, and there were no deaths. Geometric mean titres (GMTs) from an anti-spike (Wuhan) ELISA in participants aged 6-11 years were 1 EU/ml (95% CI 1-2) at baseline versus 796 EU (95% CI 161-3948, n =4) at D364. In participants aged 12-17 years, GMTs were 1 EU/ml (95% CI 1-2, n=3) at baseline versus 1432 EU/ml (95% CI 2337-6083; n=6) at D364 (2 dose regimen at 112-day interval), compared to 3 EU/ml (95% CI 0-62) at baseline versus 392 EU/ml (95% CI 24, 6493; n=3) at D364 (2 dose regimen at a 28-day interval). A two-dose regimen of ChAdOx1 nCoV-19 was immunogenic and safe in the trial population. No vaccine-related serious adverse events were reported. Immune responses persisted to 12 months in participants who did not experience breakthrough infection, This trial was registered with ISRCTN, trial number 15638344. The study was funded by the Department of Health and Social Care, through the National Institute for Health Research, and AstraZeneca.

IntroductionAustralian Aboriginal and/or Torres Strait Islander (hereafter referred to as ‘Aboriginal’) adolescents (10–24 years) experience multiple challenges to their health and well-being. However, limited evidence is available on factors influencing their health trajectories. Given the needs of this group, the young age profile of the Aboriginal population and the long-term implications of issues during adolescence, reliable longitudinal data are needed.Methods and analysisThe ‘Next Generation: Youth Well-being Study’ is a mixed-methods cohort study aiming to recruit 2250 Aboriginal adolescents aged 10–24 years from rural, remote and urban communities in Central Australia, Western Australia and New South Wales. The study assesses overall health and well-being and consists of two phases. During phase 1, we qualitatively explored the meaning of health and well-being for adolescents and accessibility of health services. During phase 2, participants are being recruited into a longitudinal cohort. Recruitment is occurring mainly through community networks and connections. At baseline, participants complete a comprehensive survey and undertake an extensive age relevant clinical assessment. Survey and clinical data will be linked to various databases including those relating to health services; medication; immunisation; hospitalisations and emergency department presentations; death registrations; education; child protection and corrective services. Participants will receive follow-up surveys approximately 2 years after their baseline visit. The ‘Next Generation’ study will fill important evidence gaps by providing longitudinal data on the health and social well-being of Aboriginal adolescents supplemented with narratives from participants to provide context.Ethics and disseminationEthics approvals have been sought and granted. Along with peer-reviewed publications and policy briefs, research findings will be disseminated via reports, booklets and other formats that will be most useful and informative to the participants and community organisations.

In Richland Creek, Haywood County, North Carolina, the invasive species, Redbreast Sunfish, Lepomis auritus (Linnaeus 1758), dominates the fish assemblage. As part of a study of the feasibility of using backpack electrofishing to selectively remove the invasive, Redbreast Sunfish were removed from three reaches of Richland Creek. The sacrificed fish were used to gain insight into the population characteristics of this population. Data on total length, wet weight and age, were recorded. Stomach contents were identified to the lowest taxon feasible, and compared to standardized invertebrate samples collected near the time of fish sampling. Fish sacrificed ranged from total lengths of 31 mm to 168 mm. Fish were found from zero to three years old, with the majority of fish being in their first or second year of life. The fish collected in sites close to a small reservoir downstream were smaller than fish collected upstream, indicating that the river population was likely a sink population to the reservoir. This population of Redbreast Sunfish ate a variety of invertebrates, as well as a fish, supporting our hypothesis that they, as many invasive species, are generalists. They showed a slight preference for chironomids, and appeared to avoid mayflies.

Efficiency models have been generally applied to rank school performance nationwide. Efficiency models have not been used, however, to explore district-level internal efficiency in Ohio. That is the purpose of this study, which is focused on how well money within education maximizes educational outputs in Ohio school districts to raise student academic achievement for all students. Specifically this study: develops a research-based formula to measure efficiency of Ohio school districts, develops financial and student performance indicators based upon general theory, reviews current literature on the research question and examines the Ohio Department of Education's accountability system. This study begins with a pilot study that includes school districts from a select geographical region in all Ohio, calculates correlation statistics to measure the strength of relationships between financial inputs and student performance outputs in Ohio school districts, and further compares and contrasts financial inputs and student performance outputs among ten specific student groups from the total population. The interpretations that result from this research are based upon the state-wide student performance accountability movement mandated by the No Child Left Behind Act and supported by research conducted by leaders in this field of research including but not limited to: Bracey, Carnoy and Loeb, Figlio, Hanushek and Raymond, Jacob and Peterson and West. The empirical model evolves from analytical frameworks that were originally used to support the belief that money has no systematic effect on student academic performance. Throughout the growth of the pilot study the empirical model develops into a study that includes not only the previously stated theory-based approach that relied on Hanushek's body of literature, but also embodies a multitude of theories including those of Hedges, Laine and Greenwald, Heckman, Kain and Rivkin, Klitgaard and Hall, Murnane and Philips, Milanowski, Kimball and Odden, Murnane and Philips and Pritchard who all support the ideology that financial inputs directly impact student performance. The final empirical model and theoretical interpretations are concerned with district efficiency and maximizing student performance.