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Nick A Francis,1 David Gillespie,2 Mandy Wootton,3 Patrick White,4 Janine Bates,2 Jennifer Richards,3 Hasse Melbye,5 Kerenza Hood,2 Christopher C Butler6 1Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, England, UK; 2Centre for Trials Research, Cardiff University, Cardiff, Wales, UK; 3Specialist Antimicrobial Chemotherapy Unit, Microbiology Cardiff, Public Health Wales, Cardiff, Wales, UK; 4School of Population Health and Environmental Sciences, King’s College London, London, England, UK; 5Department of Community Medicine, UIT the Arctic University of Norway, Tromsø, Norway; 6Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, UKCorrespondence: Nick A FrancisPrimary Care, Population Sciences and Medical Education, University of Southampton, Aldermoor Health Centre, Southampton SO16 5ST, UKEmail nick.francis@soton.ac.ukIntroduction: Identifying predictors of bacterial and viral pathogens in sputum from patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) may help direct management.Methods: We used data from a trial evaluating a C-reactive protein (CRP) point of care guided approach to managing COPD exacerbations in primary care. We used regression analyses to identify baseline clinical features, including CRP value in those randomized to testing, associated with bacterial, viral or mixed infections, defined by the presence of bacterial and viral pathogens in sputum, detected by culture or polymerase chain reaction (PCR), respectively.Results: Of 386 participants with baseline sputum samples, 79 (20.5%), 123 (31.9%), and 91 (23.6%) had bacterial, viral/atypical, and mixed bacterial/viral/atypical pathogens identified, respectively. Increasing sputum purulence assessed by color chart was associated with increased odds of finding bacterial and mixed (bacterial and viral/atypical) pathogens in sputum (area under the ROC curve (AUROC) for bacterial pathogens =0.739 (95% CI: 0.670, 0.808)). Elevated CRP was associated with increased odds of finding bacterial pathogens and mixed pathogens but did not significantly increase the AUROC for predicting bacterial pathogens over sputum color alone (AUROC for combination of sputum color and CRP = 0.776 (95% CI: 0.708, 0.843), p for comparison of models = 0.053). We found no association between the presence of sputum pathogens and other clinical or demographic features.Conclusion: Sputum purulence was the best predictor of sputum bacterial pathogens and mixed bacterial viral/atypical pathogens in patients with COPD exacerbations in our study. Elevated CRP was associated with bacterial pathogens but did not add to the predictive value of sputum purulence.Keywords: COPD, exacerbation, infection, bacteria, sputum, primary care

David Gillespie,1 Daniel Farewell,2 Lucy Brookes-Howell,1 Christopher C Butler,3 Samuel Coenen,4–6 Nick A Francis,2 Paul Little,7 Beth Stuart,7 Theo Verheij,8 Kerenza Hood1 On behalf of the GRACE consortium 1Centre for Trials Research, College of Biomedical & Life Sciences, 2Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, 3Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK; 4Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), 5Centre for General Practice, Department of Primary and Interdisciplinary Care (ELIZA), 6Clinical Epidemiology and Medical Statistics, Department of Epidemiology and Social Medicine (ESOC), University of Antwerp, Antwerp, Belgium; 7Aldermoor Health Centre, Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 8Department of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Aim: To investigate the determinants of adherence to amoxicillin in patients with acute lower respiratory tract infection.Materials and methods: Three European data sets were used. Adherence data were collected using self-reported diaries. Candidate determinants included factors relating to patient, condition, therapy, health care system/provider, and the study in which the patient participated. Logistic and Cox regression models were used to investigate the determinants of initiation, implementation, and discontinuation of amoxicillin.Results: Although initiation differed across samples, implementation and discontinuation were similar. Determinants of initiation were days waited before consulting, duration of prescription, and being in a country where a doctor-issued sick certificate is required for being off work for

Johanna Laue,1 Hasse Melbye,1 Peder A Halvorsen,1 Elena A Andreeva,2 Maciek Godycki-Cwirko,3 Anja Wollny,4 Nick A Francis,5 Mark Spigt,6 Kenny Kung,7 Mette Bech Risør1 1Department of Community Medicine, General Practice Research Unit, University of Tromsø – The Arctic University of Norway, Tromsø, Norway; 2Department of Family Medicine, Northern State Medical University, Arkhangelsk, Russia; 3Department of Family and Community Medicine, Medical University of Lodz, Lodz, Poland; 4Institute of General Practice, University Medical Center Rostock, Rostock, Germany; 5Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK; 6CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands; 7The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Purpose: To explore the decision-making of general practitioners (GPs) concerning treatment with antibiotics and/or oral corticosteroids and hospitalization for COPD patients with exacerbations.Methods: Thematic analysis of seven focus groups with 53 GPs from urban and rural areas in Norway, Germany, Wales, Poland, Russia, the Netherlands, and Hong Kong.Results: Four main themes were identified. 1) Dealing with medical uncertainty: the GPs aimed to make clear medical decisions and avoid unnecessary prescriptions and hospitalizations, yet this was challenged by uncertainty regarding the severity of the exacerbations and concerns about overlooking comorbidities. 2) Knowing the patient: contextual knowledge about the individual patient provided a supplementary framework to biomedical knowledge, allowing for more differentiated decision-making. 3) Balancing the patients’ perspective: the GPs considered patients’ experiential knowledge about their own body and illness as valuable in assisting their decision-making, yet felt that dealing with disagreements between their own and their patients’ perceptions concerning the need for treatment or hospitalization could be difficult. 4) Outpatient support and collaboration: both formal and informal caregivers and organizational aspects of the health systems influenced the decision-making, particularly in terms of mitigating potentially severe consequences of “wrong decisions” and concerning the negotiation of responsibilities.Conclusion: Fear of overlooking severe comorbidity and of further deteriorating symptoms emerged as a main driver of GPs’ management decisions. GPs consider a holistic understanding of illness and the patients’ own judgment crucial to making reasonable decisions under medical uncertainty. Moreover, GPs’ decisions depend on the availability and reliability of other formal and informal carers, and the health care systems’ organizational and cultural code of conduct. Strengthening the collaboration between GPs, other outpatient care facilities and the patients’ social network can ensure ongoing monitoring and prompt intervention if necessary and may help to improve primary care for COPD patients with exacerbations. Keywords: COPD exacerbation, antibiotics, oral corticosteroids, hospitalization, primary care, decision-making

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

Liberia developed an evidence-informed package of health services for Universal Health Coverage (UHC) based on the Disease Control Priorities 3 evidence. This paper describes the policy decisions, methods and processes adopted for prioritisation, key features of the package and lessons learnt, with special emphasis on feasibility of implementation. Package design was led by the Ministry of Health. Prioritisation of essential services was based on evidence on disease burden, cost-effectiveness, financial risk, equity, budget impact, and feasibility of implementation. Fiscal space analysis was used to assess package affordability and options for expanding the budget envelope. The final adopted package focuses on primary healthcare and comprises a core subpackage of 78 publicly financed interventions and a complementary subpackage of 50 interventions funded through cost-sharing. The estimated per capita cost to the government is US$12.28, averting around 1.2 million DALYs. Key lessons learnt are described: (1) priority setting is essential for designing affordable packages of essential services; (2) the most realistic and affordable option when domestic resources are critically limited is to focus on basic, high-impact primary health services; (3) Liberia and many other countries will continue to rely on donor funding to expand the range of essential services until more domestic resources become available; (4) national leadership and effective engagement of key stakeholders are critical for a successful package design; (5) effective implementation is less likely unless the package cost is affordable and the health system gaps are assessed and addressed. A framework of action was employed to assess the consistency with the prerequisites for an appropriate package design. Based on the framework, Liberia developed a transparent and affordable package for UHC, but the challenges to implementation require further action by the government.

This paper assessed factors influencing participation in agricultural production by government workers in the Upper West Regions of Ghana. A cross-sectional survey design was employed, using purposive and simple random sampling techniques to select 400 respondents across four (4) municipalities in the Upper West Region (UWR) for interview. Data were analyzed using the Heckman two-stage model to determine the extent to which factors critical to the participation in agricultural production by government workers. Results show that the majority (85.2 %) of government workers participate in one form or the other in agricultural production. They are specifically involved in crop production that is; food, and cash crops production as well as animal production. The need to supplement family food needs and to earn extra income was seen to condition their choice to participate in agriculture. The first and second stage predicting factors are income, access to extension, knowledge in agriculture and government policies; these were found to be statistically significant at 1 %. Time availability was significant at 5 %, however, sex, age, household size, credit availability, access to credit, passion for agriculture, scarcity of food, market access and cost of food were all found to be statistically significant at 10 %. We recommend that MoFA and its development partners in agriculture, effectively use local media and community visits to create more awareness among government workers on agricultural programmes and policies, since extension and knowledge in agriculture influence participation in agriculture production as revealed by the study in the UWR.

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT 04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

O encarceramento feminino é permeado por inúmeras problemáticas estruturais e pela ineficiência na garantia de direitos fundamentais e assistência psicológica às mulheres. Neste artigo, analisam-se os efeitos de oficinas de intervenção para a promoção do autoconceito, da empatia e de valores básicos em mulheres encarceradas. Participaram do estudo 56 mulheres, em uma Cadeia Pública, com idades entre 18 e 63 anos (M = 32,23; DP = 9,25). Quinze destas mulheres participaram do programa de intervenção, enquanto que o restante da amostra compôs o grupo controle. Ambos os grupos foram avaliados no período pré e pós-intervenção, por meio da Escala de Autoconceito, o Interpersonal Reactivity Index e o Questionário de Valores Básicos. Notas de campo e a observação participante foram utilizadas para descrever experiências significativas vivenciadas durante os encontros. Não foram encontradas variações estatisticamente significativas nos escores das escalas empregadas, o que pode estar relacionado à necessidade de adequação desses instrumentos para públicos com baixa escolarização. Em contrapartida, avalia-se que o uso de oficinas possibilitou a construção de um espaço pedagógico, com contingências muito distintas do ambiente carcerário, no qual as mulheres foram estimuladas a experimentar suas emoções e sentimentos.

Background & Aims: Prophylaxis with nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) has decreased the rate of HBV recurrence after orthotopic liver transplantation (OLT), but the duration of this prophylaxis remains debated. Our aim was to investigate the recurrence of both intrahepatic and serum HBV markers after OLT in patients receiving long-term NUC and HBIG prophylaxis. Methods: A total of 31 HBV-positive patients benefiting from OLT were prospectively enrolled in five French centres between 2012 and 2015. Tissue samples from the native liver, liver reperfusion biopsy, and 12-month post-OLT (M12) biopsy were collected. Intrahepatic HBV markers were quantified using Droplet Digital PCR. Serum hepatitis B core-related antigen (HBcrAg) and HBsAg were quantified using the Lumipulse platform. Results: Among the 31 patients, 26 were HBeAg negative and 28 had undetectable serum HBV DNA at OLT. All patients received HBIG and NUC after OLT, and serum HBV DNA was undetectable at M12. Of the 27 available native livers, 26 had detectable total HBV DNA (median, 0.045 copies/cell), 21 were positive for cccDNA (0.001 copies/cell), and 19 were positive for 3.5-kb HBV RNA (0.0004 copies/cell). Among the 14 sequential reperfusion and M12 biopsies, seven were positive for HBV markers on the reperfusion sampling, and six of them were also positive at M12. Of the 27 patients with available serum samples at M12, eight were positive for HBcrAg and five were positive for HBsAg by ultrasensitive quantification, although they were negative by conventional techniques. Overall, among the 17 patients having a matched biopsy and serum sample at M12, only one had undetectable HBV markers in both the liver and serum. Conclusions: Our results demonstrate a very early detection of viral genome in the graft and intrahepatic viral recurrence despite NUC and HBIG prophylaxis. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT02602847). Impact and Implications: In this work, we show that, despite the recommended prophylaxis based on NUC and HBIG, HBV can infect the new liver very rapidly after transplantation. Twelve months after transplantation, the majority of patients had at least one HBV marker detected in either serum or the liver. Therefore, our results demonstrate early intrahepatic viral recurrence despite NUC and HBIG therapy and underline the importance of an optimal patient compliance to the antiviral prophylaxis to prevent viral rebound.

The relationship between coach and athlete has been identified as a key factor for several positive outcomes in the sports context. Thus, the aims of this study were to analyze the association between the quality of the coach-athlete relationship (CAR) and the perception of team cohesion of youth athletes. Participants were 301 athletes, aged 15 to 17 years, who participated in the School Games of Pernambuco, Brazil. The instruments used were the Coach-Athlete Relationship Questionnaire (CART-Q) and the Group Environment Questionnaire (GEQ). Data analysis was conducted through the Structural Equation Modeling (p< .05) with team cohesion, explaining 25% of the variance of task cohesion and 15% of social cohesion. Specifically, the effect of CAR on task (β = 0.50) and social (β = 0.39) cohesion was significant (p

O presente ensaio tem como objetivo contextualizar e discutir a partir da literatura revisada os fatores que influenciaram os ingressos a optarem pelo curso de Educação Física, sobretudo a Licenciatura, à luz do quadro teórico de Pierre Bourdieu e Bernard Lahire. Metodologicamente, empregou-se uma revisão de literatura narrativa de natureza exploratória, descritiva e crítica de 24 artigos no indexador Google Scholar conjuntamente aos quadros teóricos previamente citados. Concluiu-se que esses fatores se referem ao gosto por esportes e/ou atividades físicas seguido da influência do professor de Educação Física da Educação Básica.

Modern perioperative medicine has dramatically altered the care for patients undergoing major surgery. Anaesthetic and surgical practice has been directed at mitigating the surgical stress response and reducing physiological insult. The development of standardised enhanced recovery programmes combined with minimally invasive surgical techniques has lead to reduction in length of stay, morbidity, costs, and improved outcomes. The enhanced recovery after surgery (ERAS) society and its national chapters provide a means for sharing best practice in this field and developing evidence based guidelines. Research has highlighted persisting challenges with compliance as well as ensuring the effectiveness and sustainability of ERAS. There is also a growing need for increasingly personalised care programmes as well as complex geriatric assessment of frailer patients. Continuous collection of outcome and process data combined with machine learning, offers a potentially powerful solution to delivering bespoke care pathways and optimising individual management. Long-term data from ERAS programmes remain scarce and further evaluation of functional recovery and quality of life is required.

Abstract Background The propensity of different Anopheles mosquitoes to bite humans instead of other vertebrates influences their capacity to transmit pathogens to humans. Unfortunately, determining proportions of mosquitoes that have fed on humans, i.e. Human Blood Index (HBI), currently requires expensive and time-consuming laboratory procedures involving enzyme-linked immunosorbent assays (ELISA) or polymerase chain reactions (PCR). Here, mid-infrared (MIR) spectroscopy and supervised machine learning are used to accurately distinguish between vertebrate blood meals in guts of malaria mosquitoes, without any molecular techniques. Methods Laboratory-reared Anopheles arabiensis females were fed on humans, chickens, goats or bovines, then held for 6 to 8 h, after which they were killed and preserved in silica. The sample size was 2000 mosquitoes (500 per host species). Five individuals of each host species were enrolled to ensure genotype variability, and 100 mosquitoes fed on each. Dried mosquito abdomens were individually scanned using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectrometer to obtain high-resolution MIR spectra (4000 cm−1 to 400 cm−1). The spectral data were cleaned to compensate atmospheric water and CO2 interference bands using Bruker-OPUS software, then transferred to Python™ for supervised machine-learning to predict host species. Seven classification algorithms were trained using 90% of the spectra through several combinations of 75–25% data splits. The best performing model was used to predict identities of the remaining 10% validation spectra, which had not been used for model training or testing. Results The logistic regression (LR) model achieved the highest accuracy, correctly predicting true vertebrate blood meal sources with overall accuracy of 98.4%. The model correctly identified 96% goat blood meals, 97% of bovine blood meals, 100% of chicken blood meals and 100% of human blood meals. Three percent of bovine blood meals were misclassified as goat, and 2% of goat blood meals misclassified as human. Conclusion Mid-infrared spectroscopy coupled with supervised machine learning can accurately identify multiple vertebrate blood meals in malaria vectors, thus potentially enabling rapid assessment of mosquito blood-feeding histories and vectorial capacities. The technique is cost-effective, fast, simple, and requires no reagents other than desiccants. However, scaling it up will require field validation of the findings and boosting relevant technical capacity in affected countries.

This study assessed the perception of consumers on the safety of fresh coconut in the New Juaben South Municipality of Ghana. A study was conducted with 35 coconut vendors and 210 consumers using purposive and accidental sampling techniques. Officials of the municipal food safety regulatory bodies were interviewed to get the institutional regulatory aspects of coconut vending. Descriptive statistics were processed from the survey data. Post-harvest, marketing and servicing activities of coconut vendors were identified as a major threat to food safety in the municipality. High awareness of the health benefits of tender coconut water accounts for its continuous consumption among consumers. A majority (36.2%) of consumers were of the view that vendor operations are likely to result in malaria outbreaks followed by Covid-19 infections (26.2%), cholera (20%) and dysentery (17.6%). Increased awareness through education for vendors and consumers and improved regulatory functions are recommended because of the cultural significance and health benefits of coconut consumption.

Abstract Genetically-modified animal models have significantly increased our understanding of the complex central nervous system circuits. Among these models, inducible transgenic mice whose specific gene expression can be modulated through a Cre recombinase/LoxP system are useful to study the role of specific peptides and proteins in a given population of cells. In the present study, we describe an efficient approach to selectively deliver a Cre-GFP to dorsal root ganglia (DRG) neurons. First, mice of different ages were injected in both hindpaws with a recombinant adeno-associated virus (rAAV2/9-CBA-Cre-GFP). Using this route of injection in mice at 5 days of age, we report that approximately 20% of all DRG neurons express GFP, 6 to 8 weeks after the infection. The level of infection was reduced by 50% when the virus was administered at 2 weeks of age. Additionally, the virus-mediated delivery of the Cre-GFP was also investigated via the intrathecal route. When injected intrathecally, the rAAV2/9-CBA-Cre-GFP virus infected a much higher proportion of DRG neurons than the intraplantar injection, with up to 51.6% of infected lumbar DRG neurons. Noteworthy, both routes of injection predominantly transduced DRG neurons over spinal and brain neurons.

Background: Delayed antibiotic prescribing is promoted as a strategy to reduce antibiotic consumption, but its use and its effect on antibiotic consumption in routine care is poorly described.Aim: To quantify delayed antibiotic prescribing in adults presenting in primary care with acute cough/lower respiratory tract infection (LRTI), duration of advised delay, consumption of delayed antibiotics, and factors associated with consumption.Design and Setting: Prospective observational cohort in general practices in 14 primary care networks in 13 European countries.Method: GPs recorded clinical features and antibiotic prescribing for adults presenting with an acute infective illness with cough as the dominant symptom. Patients recorded their consumption of antibiotics from any source during the 28-day follow up.Results: Two hundred and ten (6.3%) of 3368 patients with usable consultation data were prescribed delayed antibiotics. The median recommended delay period was 3 days. Seventy-five (44.4%) of the 169 with consumption data consumed the antibiotic course and a further 18 (10.7%) took another antibiotic during the study period. 50 (29.6%) started their delayed course on the day of prescription. Clinician diagnosis of upper respiratory tract/viral infection and clinician's perception of patient's wanting antibiotics were associated with less consumption of the delayed prescription. Patient's wanting antibiotics was associated with greater consumption.Conclusion: Delayed antibiotic prescribing was used infrequently for adults presenting in general practice with acute cough/LRTI. When used, the effect on antibiotic consumption was less than found in most trials. There are opportunities for standardising the intervention and promoting wider uptake. [ABSTRACT FROM AUTHOR]

ABSTRACT OBJECTIVE To evaluate the active health Ombudsman service as an instrument to evaluate the quality of delivery and birth care in the Cegonha Network of the Federal District of Brazil. METHODS This is a cross-sectional study of the telephone survey type carried out with 1,007 mothers with deliveries between October 15, 2013 and November 19, 2013 in the twelve public maternity hospitals that make up the Cegonha Network of the Federal District of Brazil. The instrument has 25 multiple choice or Likert scale questions, including sociodemographic data and acceptability evaluation in five domains: accessibility, relationship between the patient and health professionals, conditions of the structure of the service, information to the patient, and equity and opinion of the patient. We have studied qualitative or categorical variables according to the frequency and distribution of proportions. We have used the score transformed into a scale from zero to 100 for the analysis of the Likert-type scale questions. Results have been expressed as mean and standard deviation. RESULTS Access to prenatal appointments was evaluated as good or excellent by 86.1% of the participants and laboratory tests was evaluated as good or excellent by 85.2% of them. The access to imaging tests was evaluations as good or excellent by 45.7% of the women; 79.5% of the interviewees had their delivery in the maternity hospital where they sought initial care and 18.3% received a home visit by a community health agent after discharge. Most women reported that newborns were placed skin-to-skin immediately after birth, 48.9% had a companion at the time of the delivery, 76.3% were advised about the first appointment of the newborn, and 94.8% were advised on breastfeeding in the maternity hospital. Regarding the evaluation of health professionals, 85.9% of the women considered reception and cordiality as good or excellent at the prenatal care and 94.8% considered it as good or excellent at the maternity hospital. CONCLUSIONS The active health Ombudsman service has contributed to evaluate the quality of public management by allowing the incorporation of the perspective of users of the health service in the evaluation of the acceptability of the Cegonha Network in the Federal District of Brazil.

INTRODUCTION: On 19 March 2017, an outbreak of unknown etiology was reported among students at a college in Lusaka, Zambia. We investigated to confirm the outbreak, identify exposures, determine the aetiological agent, and implement preventive measures. METHODS: we conducted an unmatched case-control study. Cases and controls were selected conveniently. A suspected case was diarrhea or abdominal pains in any student at College A and Controls were asymptomatic students at College A during 18-23 March. We interviewed cases and controls about exposures to suspected food and water and collected saved food samples and swabs from food-handlers' hands and kitchen surfaces for culture. We analyzed data using Epi-info v 7.2 (Atlanta, Georgia). RESULTS: we identified 59 suspected case-patients. Predominant symptoms were diarrhea (n = 51.83%) and abdominal pains (n = 44.75%). The outbreak started on 18 March, peaked on 19, and concluded on 20 March. We interviewed 30 case-patients and 71 controls. Exposures associated with increased odds of illness included eating food served at dinner on Saturday (18 March) in school cafeteria (OR = 5.8, 95% CI = 2.0-16.7); specifically, eating beans at Saturday dinner (OR = 21.6, 95% CI = 4.5-104) and drinking water supplied at school (OR = 8.8, 95% CI = 1.45-53.6). Samples from all food-handlers (n = 13) yielded Staphylococcus aureus and all food samples (n = 3) yielded Escherichia coli, Staphylococcus aureus and fecal coliforms. CONCLUSION: the results suggest a foodborne outbreak caused by consumption of contaminated food served at dinner on 18 March at College A. We educated the food handlers and school management about the importance of disinfection of preparation surfaces, supervision of food handling and handwashing practices.

Abstract AIMS to diagnose continuing education initiatives and training needs of physical education teachers. The frequency, limitations and alternatives to continuing education were characterized and self-assessment areas of knowledge essential to teaching were analyzed. METHODS Data were obtained from 18 beginning teachers, using the Professional Career Characterization Questionnaire, an inventory of needs and characterization of continuing training and self-assessment of skills in areas of knowledge essential to teaching. Qualitative data were systematized and quantitative data analyzed by descriptive statistics. RESULTS Teachers performed 78 continuing training activities over the last four years, 43 in the technical area of physical education and 28 in school-based Physical Education. The most attended subjects were short-duration and graduate courses. The main limitations identified were the financial and time constraints to training. Self-assessment of the teaching areas was deemed to be sufficient, indicating a margin for new learning. CONCLUSION The teachers showed commitment to their training, with a focus on teaching and awareness of its importance in professional development.

Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation.

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. The benefits from antibiotic treatment for common RTIs have been shown to be largely overstated. Nevertheless, serious infections do occur. Currently, no clinical features or diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Consultation rate and prescribing rate trends are described, evidence of increasing rates of complications are discussed, and studies and the association with antibiotic prescribing are examined. Methods of improving diagnosis and identifying those patients who are at increased risk of complications from RTIs, using clinical scoring systems, biomarkers, and point of care tests are also discussed. The evidence for alternative management options for RTIs are summarised and the methods for changing public and clinicians' beliefs about antibiotics, including ways in which we can improve clinician-patient communication skills for management of RTIs, are described. [ABSTRACT FROM AUTHOR]

BACKGROUND: Respiratory tract infections in children result in more primary care consultations than any other acute condition, and are the most common reason for prescribing antibiotics (which are largely unnecessary). About a fifth of children consult again for the same illness episode. Providing parents with written information on respiratory tract infections may result in a reduction in re-consultation rates and antibiotic prescribing for these illnesses. Asking clinicians to provide and discuss the information during the consultation may enhance effectiveness. This paper outlines the protocol for a study designed to evaluate the use of a booklet on respiratory tract infections in children within primary care consultations. METHODS/DESIGN: This will be a cluster randomised controlled trial. General practices will be randomised to provide parents consulting because their child has an acute respiratory tract infection with either an interactive booklet, or usual care. The booklet provides information on the expected duration of their child's illness, the likely benefits of various treatment options, signs and symptoms that should prompt re-consultation, and symptomatic treatment advice. It has been designed for use within the consultation and aims to enhance communication through the use of specific prompts. Clinicians randomised to using the interactive booklet will receive online training in its use. Outcomes will be assessed via a telephone interview with the parent two weeks after first consulting. The primary outcome will be the proportion of children who re-consult for the same illness episode. Secondary outcomes include: antibiotic use, parental satisfaction and enablement, and illness costs. Consultation rates for respiratory tract infections for the subsequent year will be assessed by a review of practice notes. DISCUSSION: Previous studies in adults and children have shown that educational interventions can result in reductions in re-consultation rates and use of antibiotics for respiratory tract infections. This will be the first study to determine whether providing parents with a booklet on respiratory tract infections in children, and discussing it with them during the consultation, reduces re-consultations and antibiotic use for the same illness without reducing satisfaction with care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46104365. [ABSTRACT FROM AUTHOR]

RESUMO: O processo de formação do profissional de saúde tem se modificado na busca de educar profissionais com uma visão integral e que proponham mudanças na sociedade. Dentro desse contexto, a saúde da pessoa com deficiência merece destaque, tendo em vista que essas pessoas têm mais barreiras de acessos aos serviços prestados por esses profissionais, tais como dificuldade de comunicação, empatia do profissional, barreiras arquitetônicas, instrumentais, entre outras. Logo, este estudo objetiva analisar como duas universidades públicas discutem a saúde da pessoa com deficiência dentro do currículo do profissional de saúde. Para isso, analisaram-se projetos pedagógicos de oito cursos de Saúde. Concluiu-se que os projetos analisados não garantem uma formação integral no que tange à atenção à saúde da pessoa com deficiência.

RESUMO: O processo de formação do profissional de saúde tem se modificado na busca de educar profissionais com uma visão integral e que proponham mudanças na sociedade. Dentro desse contexto, a saúde da pessoa com deficiência merece destaque, tendo em vista que essas pessoas têm mais barreiras de acessos aos serviços prestados por esses profissionais, tais como dificuldade de comunicação, empatia do profissional, barreiras arquitetônicas, instrumentais, entre outras. Logo, este estudo objetiva analisar como duas universidades públicas discutem a saúde da pessoa com deficiência dentro do currículo do profissional de saúde. Para isso, analisaram-se projetos pedagógicos de oito cursos de Saúde. Concluiu-se que os projetos analisados não garantem uma formação integral no que tange à atenção à saúde da pessoa com deficiência.

Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted two-photon imaging experiments in auditory cortex of awake mice and collected video of free-roaming mouse behavior, both at baseline and during psilocybin treatment. In comparison with pre-dose neural activity, a 2 mg/kg ip dose of psilocybin initially increased the amplitude of neural responses to sound. Thirty minutes post-dose, behavioral activity and neural response amplitudes decreased, yet functional connectivity increased. In contrast, control mice given intraperitoneal saline injections showed no significant changes in either neural or behavioral activity across conditions. Notably, neuronal stimulus selectivity remained stable during psilocybin treatment, for both tonotopic cortical maps and single-cell pure-tone frequency tuning curves. Our results mirror similar findings regarding the effects of serotonergic psychedelics in visual cortex and suggest that psilocybin modulates the balance of intrinsic versus stimulus-driven influences on neural activity in auditory cortex. NEW & NOTEWORTHY Recent studies have shown promising therapeutic potential for psychedelics in treating neuropsychiatric conditions. Musical experience during psilocybin-assisted therapy is predictive of treatment outcome, yet little is known about how psilocybin affects auditory processing. Here, we conducted two-photon imaging experiments in auditory cortex of awake mice that received a dose of psilocybin. Our results suggest that psilocybin modulates the roles of intrinsic neural activity versus stimulus-driven influences on auditory perception.

Background: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic., Aim: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-β1a (SNG001) in this setting., Design & Setting: Randomised, double-blind, parallel-group study, which was conducted remotely., Method: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely., Results: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related., Conclusion: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser., (Copyright © 2023, The Authors.)

Background: Sore throat is a common problem and a common reason for the overuse of antibiotics. A web-based tool that helps people assess their sore throat, through the use of clinical prediction rules, taking throat swabs or saliva samples, and taking throat photographs, has the potential to improve self-management and help identify those who are the most and least likely to benefit from antibiotics., Objective: We aimed to develop a web-based tool to help patients and parents or carers self-assess sore throat symptoms and take throat photographs, swabs, and saliva samples for diagnostic testing. We then explored the acceptability and feasibility of using the tool in adults and children with sore throats., Methods: We used the Person-Based Approach to develop a web-based tool and then recruited adults and children with sore throats who participated in this study by attending general practices or through social media advertising. Participants self-assessed the presence of FeverPAIN and Centor score criteria and attempted to photograph their throat and take throat swabs and saliva tests. Study processes were observed via video call, and participants were interviewed about their views on using the web-based tool. Self-assessed throat inflammation and pus were compared to clinician evaluation of patients' throat photographs., Results: A total of 45 participants (33 adults and 12 children) were recruited. Of these, 35 (78%) and 32 (71%) participants completed all scoring elements for FeverPAIN and Centor scores, respectively, and most (30/45, 67%) of them reported finding self-assessment relatively easy. No valid response was provided for swollen lymph nodes, throat inflammation, and pus on the throat by 11 (24%), 9 (20%), and 13 (29%) participants respectively. A total of 18 (40%) participants provided a throat photograph of adequate quality for clinical assessment. Patient assessment of inflammation had a sensitivity of 100% (3/3) and specificity of 47% (7/15) compared with the clinician-assessed photographs. For pus on the throat, the sensitivity was 100% (3/3) and the specificity was 71% (10/14). A total of 89% (40/45), 93% (42/45), 89% (40/45), and 80% (30/45) of participants provided analyzable bacterial swabs, viral swabs, saliva sponges, and saliva drool samples, respectively. Participants were generally happy and confident in providing samples, with saliva samples rated as slightly more acceptable than swab samples., Conclusions: Most adult and parent participants were able to use a web-based intervention to assess the clinical features of throat infections and generate scores using clinical prediction rules. However, some had difficulties assessing clinical signs, such as lymph nodes, throat pus, and inflammation, and scores were assessed as sensitive but not specific. Many participants had problems taking photographs of adequate quality, but most were able to take throat swabs and saliva samples., (©Mark Lown, Kirsten A Smith, Ingrid Muller, Catherine Woods, Emma Maund, Kirsty Rogers, Taeko Becque, Gail Hayward, Michael Moore, Paul Little, Margaret Glogowska, Alastair Hay, Beth Stuart, Efi Mantzourani, Christopher R Wilcox, Natalie Thompson, Nick A Francis. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.12.2023.)

Measures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity-that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations., (© 2023. The Author(s).)

Background: Clinical uncertainty in primary care regarding the prognosis of children with respiratory tract infections contributes to the unnecessary use of antibiotics. Improved identification of children at low risk of future hospitalisation might reduce clinical uncertainty. A National Institute for Health and Care Research-funded 5-year programme (RP-PG-0608-10018) was used to develop and feasibility test an intervention., Objectives: The aim of the children with acute cough randomised controlled trial was to reduce antibiotic prescribing among children presenting with acute cough and respiratory tract infection without increasing hospital admission., Design: An efficient, pragmatic open-label, two-arm trial (with embedded qualitative and health economic analyses) using practice-level randomisation using routinely collected data as the primary outcome., Setting: General practitioner practices in England., Participants: General practitioner practices using the Egton Medical Information Systems ® patient-record system for children aged 0-9 years presenting with a cough or upper respiratory tract infection. Recruited by Clinical Research Networks and Clinical Commissioning Groups., Intervention: Comprised: (1) elicitation of parental concerns during consultation; (2) a clinician-focused prognostic algorithm to identify children with acute cough and respiratory tract infection at low, average or elevated risk of hospitalisation in the next 30 days accompanied by prescribing guidance, (3) provision of a printout for carers including safety-netting advice., Main Outcome Measures: Co-primaries using the practice list-size for children aged 0-9 years as the denominator: rate of dispensed amoxicillin and macrolide items at each practice (superiority comparison) from NHS Business Services Authority ePACT2 and rate of hospital admission for respiratory tract infection (non-inferiority comparison) from Clinical Commissioning Groups, both routinely collected over 12 months., Results: Of the 310 practices required, 294 (95%) were recruited (144 intervention and 150 controls) with 336,496 registered 0-9-year-olds (5% of all 0-9-year-old children in England) from 47 Clinical Commissioning Groups. Included practices were slightly larger than those not included, had slightly lower baseline dispensing rates and were located in more deprived areas (reflecting the distribution for practice postcodes nationally). Twelve practices (4%) subsequently withdrew (six related to the pandemic). The median number of times the intervention was used was 70 per practice (by a median of 9 clinicians) over 12 months. There was no evidence that the antibiotic dispensing rate in the intervention practices [0.155 (95% confidence interval 0.135 to 0.179)] differed to controls [0.154 (95% confidence interval 0.130 to 0.182), relative risk= 1.011 (95% confidence interval 0.992 to 1.029); p = 0.253]. There was, overall, a reduction in dispensing levels and intervention usage during the pandemic. The rate of hospitalisation for respiratory tract infection in the intervention practices [0.019 (95% confidence interval 0.014 to 0.026)] compared to the controls [0.021 (95% confidence interval 0.014 to 0.029)] was non-inferior [relative risk = 0.952 (95% confidence interval 0.905 to 1.003)]. The qualitative evaluation found the clinicians liked the intervention, used it as a supportive aid, especially with borderline cases but that it, did not always integrate well within the consultation flow and was used less over time. The economic evaluation found no evidence of a difference in mean National Health Service costs between arms; mean difference -£1999 (95% confidence interval -£6627 to 2630)., Conclusions: The intervention was feasible and subjectively useful to practitioners, with no evidence of harm in terms of hospitalisations, but did not impact on antibiotic prescribing rates., Future Work and Limitations: Although the intervention does not appear to change prescribing behaviour, elements of the approach may be used in the design of future interventions., Trial Registration: This trial is registered as ISRCTN11405239 (date assigned 20 April 2018) at www.controlled-trials.com (accessed 5 September 2022). Version 4.0 of the protocol is available at: https://www.journalslibrary.nihr.ac.uk/ (accessed 5 September 2022)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (NIHR award ref: 16/31/98) programme and is published in full in Health Technology Assessment ; Vol. 27, No. 32. See the NIHR Funding and Awards website for further award information.

Background: Antibiotics are commonly prescribed for children with lower respiratory tract infections (LRTIs), fuelling antibiotic resistance, and there are few prognostic tools available to inform management., Aim: To externally validate an existing prognostic model (STARWAVe) to identify children at low risk of illness progression, and if model performance was limited to develop a new internally validated prognostic model., Design and Setting: Prospective cohort study with a nested trial in a primary care setting., Method: Children aged 6 months to 12 years presenting with uncomplicated LRTI were included in the cohort. Children were randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or if not randomised they participated in a parallel observational study to maximise generalisability. Baseline clinical data were used to predict adverse outcome (illness progression requiring hospital assessment)., Results: A total of 758 children participated ( n = 432 trial, n = 326 observational). For predicting illness progression the STARWAVe prognostic model had moderate performance (area under the receiver operating characteristic [AUROC] 0.66, 95% confidence interval [CI] = 0.50 to 0.77), but a new, internally validated model (seven items: baseline severity; respiratory rate; duration of prior illness; oxygen saturation; sputum or a rattly chest; passing urine less often; and diarrhoea) had good discrimination (bootstrapped AUROC 0.83, 95% CI = 0.74 to 0.92) and calibration. A three-item model (respiratory rate; oxygen saturation; and sputum or a rattly chest) also performed well (AUROC 0.81, 95% CI = 0.70 to 0.91), as did a score (ranging from 19 to 102) derived from coefficients of the model (AUROC 0.78, 95% CI = 0.67 to 0.88): a score of <70 classified 89% ( n = 600/674) of children having a low risk (<5%) of progression of illness., Conclusion: A simple three-item prognostic score could be useful as a tool to identify children with LRTI who are at low risk of an adverse outcome and to guide clinical management., (© The Authors.)

Objective: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents., Methods: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin., Results: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home., Discussion: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions., Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses., Design: We will develop deeper understanding of 'burdensomeness' and 'complexity' through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential 'preventable moments', defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee, member of the NICE Decision Support Unit (DSU), and associate member of the NICE Technical Support Unit (TSU). She has served as a paid consultant to the pharmaceutical industry, providing unrelated methodological advice. She reports teaching fees from the Association of British Pharmaceutical Industry (ABPI) and the University of Bristol., (© The Author(s) 2023.)

Background: Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath)., Objectives: To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups., Design: Placebo-controlled trial with qualitative, observational and cost-effectiveness studies., Setting: UK general practices., Participants: Children aged 1-12 years with acute uncomplicated lower respiratory tract infections., Outcomes: The primary outcome was the duration in days of symptoms rated moderately bad or worse (measured using a validated diary). Secondary outcomes were symptom severity on days 2-4 (0 = no problem to 6 = as bad as it could be); symptom duration until very little/no problem; reconsultations for new or worsening symptoms; complications; side effects; and resource use., Methods: Children were randomised to receive 50 mg/kg/day of oral amoxicillin in divided doses for 7 days, or placebo using pre-prepared packs, using computer-generated random numbers by an independent statistician. Children who were not randomised could participate in a parallel observational study. Semistructured telephone interviews explored the views of 16 parents and 14 clinicians, and the data were analysed using thematic analysis. Throat swabs were analysed using multiplex polymerase chain reaction., Results: A total of 432 children were randomised (antibiotics, n = 221; placebo, n = 211). The primary analysis imputed missing data for 115 children. The duration of moderately bad symptoms was similar in the antibiotic and placebo groups overall (median of 5 and 6 days, respectively; hazard ratio 1.13, 95% confidence interval 0.90 to 1.42), with similar results for subgroups, and when including antibiotic prescription data from the 326 children in the observational study. Reconsultations for new or worsening symptoms (29.7% and 38.2%, respectively; risk ratio 0.80, 95% confidence interval 0.58 to 1.05), illness progression requiring hospital assessment or admission (2.4% vs. 2.0%) and side effects (38% vs. 34%) were similar in the two groups. Complete-case ( n = 317) and per-protocol ( n = 185) analyses were similar, and the presence of bacteria did not mediate antibiotic effectiveness. NHS costs per child were slightly higher (antibiotics, £29; placebo, £26), with no difference in non-NHS costs (antibiotics, £33; placebo, £33). A model predicting complications (with seven variables: baseline severity, difference in respiratory rate from normal for age, duration of prior illness, oxygen saturation, sputum/rattly chest, passing urine less often, and diarrhoea) had good discrimination (bootstrapped area under the receiver operator curve 0.83) and calibration. Parents found it difficult to interpret symptoms and signs, used the sounds of the child's cough to judge the severity of illness, and commonly consulted to receive a clinical examination and reassurance. Parents acknowledged that antibiotics should be used only when 'necessary', and clinicians noted a reduction in parents' expectations for antibiotics., Limitations: The study was underpowered to detect small benefits in key subgroups., Conclusion: Amoxicillin for uncomplicated lower respiratory tract infections in children is unlikely to be clinically effective or to reduce health or societal costs. Parents need better access to information, as well as clear communication about the self-management of their child's illness and safety-netting., Future Work: The data can be incorporated in the Cochrane review and individual patient data meta-analysis., Trial Registration: This trial is registered as ISRCTN79914298., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 27, No. 9. See the NIHR Journals Library website for further project information.

Objective: To assess whether an easy-to-use multifaceted intervention for children presenting to primary care with respiratory tract infections would reduce antibiotic dispensing, without increasing hospital admissions for respiratory tract infection., Design: Two arm randomised controlled trial clustered by general practice, using routine outcome data, with qualitative and economic evaluations., Setting: English primary care practices using the EMIS electronic medical record system., Participants: Children aged 0-9 years presenting with respiratory tract infection at 294 general practices, before and during the covid-19 pandemic., Intervention: Elicitation of parental concerns during consultation; a clinician focused prognostic algorithm to identify children at very low, normal, or elevated 30 day risk of hospital admission accompanied by antibiotic prescribing guidance; and a leaflet for carers including safety netting advice., Main Outcome Measures: Rate of dispensed amoxicillin and macrolide antibiotics (superiority comparison) and hospital admissions for respiratory tract infection (non-inferiority comparison) for children aged 0-9 years over 12 months (same age practice list size as denominator)., Results: Of 310 practices needed, 294 (95%) were randomised (144 intervention and 150 controls) representing 5% of all registered 0-9 year olds in England. Of these, 12 (4%) subsequently withdrew (six owing to the pandemic). Median intervention use per practice was 70 (by a median of 9 clinicians). No evidence was found that antibiotic dispensing differed between intervention practices (155 (95% confidence interval 138 to 174) items/year/1000 children) and control practices (157 (140 to 176) items/year/1000 children) (rate ratio 1.011, 95% confidence interval 0.992 to 1.029; P=0.25). Pre-specified subgroup analyses suggested reduced dispensing in intervention practices with fewer prescribing nurses, in single site (compared with multisite) practices, and in practices located in areas of lower socioeconomic deprivation, which may warrant future investigation. Pre-specified sensitivity analysis suggested reduced dispensing among older children in the intervention arm (P=0.03). A post hoc sensitivity analysis suggested less dispensing in intervention practices before the pandemic (rate ratio 0.967, 0.946 to 0.989; P=0.003). The rate of hospital admission for respiratory tract infections in the intervention practices (13 (95% confidence interval 10 to 18) admissions/1000 children) was non-inferior compared with control practices (15 (12 to 20) admissions/1000 children) (rate ratio 0.952, 0.905 to 1.003)., Conclusions: This multifaceted antibiotic stewardship intervention for children with respiratory tract infections did not reduce overall antibiotic dispensing or increase respiratory tract infection related hospital admissions. Evidence suggested that in some subgroups and situations (for example, under non-pandemic conditions) the intervention slightly reduced prescribing rates but not in a clinically relevant way., Trial Registration: ISRCTN11405239ISRCTN registry ISRCTN11405239., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the NIHR Health Technology Assessment programme; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; AH is a member of the NIHR Efficacy and Mechanism Evaluation Committee; JAL is a member of a clinical trials unit in receipt of NIHR support funding; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Non-pharmaceutical interventions (NPIs), such as handwashing, social distancing and face mask wearing, have been widely promoted to reduce the spread of COVID-19. This study aimed to explore the relationship between self-reported use of NPIs and COVID-19 infection., Methods: We conducted an online questionnaire study recruiting members of the UK public from November 2020 to May 2021. The association between self-reported COVID-19 illness and reported use of NPIs was explored using logistic regression and controlling for participant characteristics, month of questionnaire completion, and vaccine status. Participants who had been exposed to COVID-19 in their household in the previous 2 weeks were excluded., Results: Twenty-seven thousand seven hundred fifty-eight participants were included and 2,814 (10.1%) reported having a COVID-19 infection. The odds of COVID-19 infection were reduced with use of a face covering in unadjusted (OR 0.17 (95% CI: 0.15 to 0.20) and adjusted (aOR 0.19, 95% CI 0.16 to 0.23) analyses. Social distancing (OR 0.27, 95% CI: 0.22 to 0.31; aOR 0.35, 95% CI 0.28 to 0.43) and handwashing when arriving home (OR 0.57, 95% CI 0.46 to 0.73; aOR 0.63, 95% CI: 0.48 to 0.83) also reduced the odds of COVID-19. Being in crowded places of 10-100 people (OR 1.89, 95% CI: 1.70 to 2.11; aOR 1.62, 95% CI: 1.42 to 1.85) and > 100 people (OR 2.33, 95% CI: 2.11 to 2.58; aOR 1.73, 95% CI: 1.53 to 1.97) were both associated with increased odds of COVID-19 infection. Handwashing before eating, avoiding touching the face, and cleaning things with virus on were all associated with increased odds of COVID-19 infections., Conclusions: This large observational study found evidence for strong protective effects for individuals from use of face coverings, social distancing (including avoiding crowded places) and handwashing on arriving home on developing COVID-19 infection. We also found evidence for an increased risk associated with other behaviours, possibly from recall bias., (© 2023. The Author(s).)

Background: There is a lack of evidence regarding post-consultation symptom trajectories for patients with respiratory tract infections (RTIs) and whether patient characteristics can be used to predict illness duration., Aim: To describe symptom trajectories in patients with RTIs, and assess baseline characteristics and adverse events associated with trajectories., Design and Setting: The study included data about 9103 adults and children from 12 primary care studies., Method: A latent class-informed regression analysis of individual patient data from randomised controlled trials and observational cohort studies was undertaken. Post-consultation symptom trajectory (severity and duration), re-consultation with same or worsening illness, and admission to hospital were assessed., Results: In total, 90% of participants recovered from all symptoms by 28 days, regardless of antibiotic prescribing strategy (none, immediate, and delayed antibiotics). For studies of RTI with cough as a dominant symptom ( n = 5314), four trajectories were identified: 'rapid (6 days)' (90% of participants recovered within 6 days) in 52.0%; 'intermediate (10 days)' (28.9%); 'slow progressive improvement (27 days)' (12.5%); and 'slow improvement with initial high symptom burden (27 days)' (6.6%). For cough, being aged 16-64 years (odds ratio [OR] 2.57, 95% confidence interval [CI] = 1.72 to 3.85 compared with <16 years), higher presenting illness baseline severity (OR 1.51, 95% CI = 1.12 to 2.03), presence of lung disease (OR 1.78, 95% CI = 1.44 to 2.21), and median and above illness duration before consultation (≥7 days) (OR 1.99, 95% CI = 1.68 to 2.37) were associated with slower recovery (>10 days) compared with faster recovery (≤10 days). Re-consultations and admissions to hospital for cough were higher in those with slower recovery (ORs: 2.15, 95% CI = 1.78 to 2.60 and 7.42, 95% CI = 3.49 to 15.78, respectively)., Conclusion: Older patients presenting with more severe, longer pre-consultation symptoms and chronic lung disease should be advised they are more likely to experience longer post-consultation illness durations, and that recovery rates are similar with and without antibiotics., (© The Authors.)

Background: Antibiotics are commonly prescribed for children with chest infections but there is little randomised evidence and trials commonly recruit selected populations, which undermines their applicability., Aim: To document the effectiveness of antibiotics for chest infections in children., Design and Setting: This was a prospective cohort study with nested trial in primary care., Method: Children aged 1-12 years presenting with uncomplicated lower respiratory tract infections were included in the cohort. Children were either randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or participated in a parallel observational study, where propensity scores controlled for confounding by indication. The outcomes were duration of symptoms rated moderately bad or worse (primary outcome) and illness progression requiring hospital assessment., Results: A total of 764 children participated (438 trial, 326 observational), and children were more unwell than in previous cohorts (more sputum, fever, shortness of breath). Children had been unwell for a median of 5-6 days, and symptoms rated moderately bad or worse lasted another 6 days when no antibiotics were given.With antibiotics there was a non-significant reduction of approximately 1 day in duration of symptoms rated moderately bad or worse for the whole cohort (hazard ratio [HR] 1.16, 95% confidence interval [CI] = 0.95 to 1.41), similar to the trial alone (HR 1.13, 95% CI = 0.90 to 1.43). The effect of antibiotic treatment on secondary outcomes was also non-significant., Conclusion: Antibiotics for uncomplicated chest infections, even in a sample of more unwell children, are unlikely to be clinically very effective., (© The Authors.)