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Study protocol for evaluating delayed antibiotic prescribing to promote rational antibiotic use in primary healthcare institutions in China: a pragmatic, multicentre, open-label, clustered-randomised controlled trial

Por: Chen · S. · Ko · W. · Li · W. · Xiao · R. · Du · F. · Zhang · J. · Wu · S. · Zheng · B. · Zhu · N. J. · Ahmad · R. · Little · P. · Guan · X. · Shi · L. · Wushouer · H.
Introduction

Delayed antibiotic prescribing (DAP) has demonstrated efficacy in reducing inappropriate antibiotic use for uncomplicated respiratory tract infections (uRTIs) in primary care across high-income countries. However, evidence regarding its effectiveness in low-income and middle-income countries remains limited. This cluster-randomised controlled trial (cRCT) aims to evaluate the effectiveness of DAP for optimising antibiotic use in primary healthcare institutions (PHIs) in China.

Methods and analysis

We designed a pragmatic, multicentre, open-label, three-arm cRCT in adult patients with uRTIs. The study will involve 12 PHIs in Korla City of China. Participating institutions will be randomised at a 1:1:1 ratio to three parallel arms: (1) DAP-intervention arm, (2) Immediate antibiotic prescribing comparator arm and (3) Usual care (observational arm). The primary outcome is symptom duration. Secondary outcomes include symptom severity, antibiotic use, adverse events, patient satisfaction and patient belief regarding antibiotic efficacy.

Ethics and dissemination

Ethics committee approval of this study was obtained from Peking University Institution Review Board (IRB00001052-24169). The findings will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Trial registration number

ChiCTR2500097330.

Two years and counting: a prospective cohort study on the scope and severity of post-COVID symptoms across diverse patient groups in the Netherlands--insights from the CORFU study

Por: Klein · D. O. · Waardenburg · S. F. · Janssen · E. B. N. J. · Wintjens · M. S. J. N. · Imkamp · M. · Heemskerk · S. C. M. · Birnie · E. · Bonsel · G. J. · Warle · M. C. · Jacobs · L. M. C. · Hemmen · B. · Verbunt · J. · van Bussel · B. C. T. · van Santen · S. · Kietelaer · B. L. J.
Importance

Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).

Objective

We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.

Design

The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).

Setting

In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.

Participants

Former COVID-19 patients and controls participated in this cohort study.

Main outcomes and measures

Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Results

A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p

Conclusions

Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.

Trial registration number

The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).

Socioeconomic diversity of doctors in the United Kingdom: a cross-sectional study of 10 years of Labour Force Survey social mobility data

Por: Cheetham · N. J. · Cantle · F. · Guise · A. · Steves · C. J.
Objectives

To estimate the association between socioeconomic background (derived from household main earner occupation when the survey respondent was aged 14 years old) and likelihood of working as a doctor in adulthood in the UK, and estimate how associations varied over time for respondents who turned 18 years old in different decades.

Design

Observational study of 10 years of pooled data from a nationally representative government survey.

Setting

The United Kingdom (UK).

Participants

358 934 respondents to the UK Office for National Statistics Labour Force Survey between July 2014 and September 2023. Respondents aged 22 years old or below or retired respondents aged 65 years old and above were excluded.

Main outcome measures

Whether the respondent was currently working as a medical practitioner (doctor).

Results

2772 respondents were currently working as doctors (0.8% of respondents). 13% of doctors were from working-class backgrounds (National Statistics Socio-economic Classification 5–8), compared with 43% of non-doctor respondents, while 69% of doctors came from professional backgrounds (vs 32% of non-doctors) (unadjusted proportions). From multivariable Poisson regression models adjusting for year of survey, the year the respondent turned 18, sex, country of birth and ethnic group, the likelihood of being a doctor varied largely according to socioeconomic background, with those from professional backgrounds 3 times and 6 times more likely to become doctors than those from intermediate backgrounds and working class backgrounds, respectively (average predicted probability: 1.6% vs 0.5% vs 0.3%). Respondents growing up in households where the main earner was a doctor were by far the most likely to themselves report working as a doctor (average predicted probability: 10.1%), 15-fold more likely than all respondents with non-doctor backgrounds (risk ratio=15.0, 95% CIs 13.4 to 16.7), and between 3 times and 100 times more likely when compared with other specific occupation groups. Stratified analyses suggested socioeconomic inequalities were highly stable over time among respondents who turned 18 between the 1960s and the 2000s, and then weak evidence of decreasing diversity from 2010 to 2018.

Conclusions

There are large, persistent and potentially widening inequalities in the socioeconomic background of doctors working in the UK between 2014 and 2023, leading to doctors being highly socioeconomically unrepresentative of the general UK population. New data collections on the socioeconomic background of working doctors are needed to monitor this inequality and understand its effects on patient care. Increased and/or alternative efforts may be needed to address this entrenched inequality and improve social mobility into medicine.

Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study: a protocol for a multicentre phase 1 safety trial of melatonin to augment therapeutic hypothermia for moderate/severe hypoxic ischaemic encephalopathy

Por: Pang · R. · Macneil · A. · Wadke · A. · Jaami · Y. · Marlow · N. · Standing · J. F. · Dehbi · H.-M. · Tranter · P. · Robertson · N. J. · on behalf of the ACUMEN Consortium · Allegaert · Becher · Boardman · Boylan · Cowan · Dehbi · Foran · Hunt · Jaami · Kendall · MacNeil · Mahaveer
Introduction

Neonatal death and later disability remain common sequelae of hypoxic-ischaemic encephalopathy (HIE) despite the now standard use of therapeutic hypothermia (HT). New therapeutic approaches to brain protection are required. Melatonin is an indolamine hormone with free-radical scavenging, antiapoptotic, anti-inflammatory and gene regulatory neuroprotective properties, which has extensive preclinical evidence of safety and efficacy. Pharmacokinetic (PK) data suggest it is necessary to reach melatonin levels of 15–30 mg/L within 6–8 hours of hypoxia-ischaemia for brain protection. We developed a novel Good Manufacturing Practice (GMP) grade melatonin in ethanol 50 mg/mL solution for intravenous use. In preclinical studies, ethanol is an adjuvant excipient with additional neuroprotective benefit; optimised dosing protocols can achieve therapeutic melatonin levels while limiting blood alcohol concentrations (BACs).

Methods and analysis

The Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study is a first-in-human, international, multicentre, phase 1 safety study of intravenous melatonin in babies with moderate/severe HIE receiving HT. Sixty babies will be studied over two phases: a dose escalation study including four dose levels to establish the recommended phase 2 dose (RP2D), followed by a 6-month cohort expansion study of RP2D to further characterise PKs and affirm safety. Participants will receive a 2-hour intravenous infusion of melatonin within 6 hours of birth, followed by five maintenance doses every 12 hours to cover the period of HT. Plasma melatonin and BACs will be monitored. The RP2D will be based on the attainment of therapeutic melatonin levels while limiting BACs and the frequency of dose-limiting events (DLEs). A Bayesian Escalation with Overdose Control approach will be used to estimate the risk of DLE per dose level, with a target level of

Ethics and dissemination

Approval has been given by the London Central National Health Service Health Research Authority Ethics Committee (25/LO/0170) and UK Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. Separate approvals have been sought in Ireland and Australia. Dissemination will be via peer-reviewed journals, conference presentations, public registries and plain language summaries for parent/legal guardian(s), in accordance with national requirements.

Trial registration number

ISRCTN61218504. EU CT: 2025-520538-49-00.

Protocol version

Publication based on the UK protocol V.3.0, 08 May 2025

Hospital discharge communication problems in 10 high-income nations: a secondary analysis of an international health policy survey

Por: Ambade · P. N. · Hoffman · Z. · Mehra · K. · Gunja · M. · Yi · M. · MacKinnon · B. H. · MacKinnon · N. J.
Objectives

We aimed to determine the prevalence of hospital discharge communication problems in adults of 10 high-income nations and the associated factors.

Design

Secondary analysis of cross-sectional survey data.

Setting

2023 Commonwealth Fund International Health Policy Survey for Adults, including data from residents of Australia, Canada, France, Germany, the Netherlands, New Zealand, Sweden, Switzerland, the UK and the USA.

Participants

3763 survey respondents aged 18 and older who reported hospitalisation at least one time in the past 2 years.

Primary and secondary outcome measures

Our primary outcome measure is poor discharge communication (PDC), which is a composite variable comprising three questions regarding the provision of written information, follow-up arrangement and discussion of medications at time of discharge.

Results

The overall PDC rate was 17.1%, with the highest in Germany (19.7%) and the lowest in the Netherlands (9.2%). No follow-up arrangement was the most commonly reported problem (22.8%). Respondents who concerned about social service needs and mental health issues were more likely to report PDC.

Conclusions

Providers should consider factors which impact PDC at hospital discharge and tailor communication appropriately. Hospitals, communities and countries should work towards policies that address underlying issues related to social determinants of health, including support for lower-income patients, improved treatment access for patients with physical and mental health conditions, and food and housing stability.

Interventions with milk proteins supplementation combined with exercise on musculoskeletal function in older adults with sarcopenia, osteoporosis and osteosarcopenia: a systematic review protocol of randomised controlled trials

Por: Brito · M. D. · Neto · N. J. · Gomes · C. d. S. · Barbosa Sales · W. · Guerra · G. C. B. · Guerra · R. O.
Introduction

Sarcopenia, osteoporosis and osteosarcopenia are conditions prevalent in ageing that impair muscle strength and bone density, increasing the risks of fractures, falls, disability and mortality. Recent studies highlight the benefits of milk protein supplementation (MPS) combined with exercises to improve musculoskeletal health in the older population. This systematic review protocol will enable the production of a compilation of evidence that will elucidate the effects of MPS combined with aerobic exercise, resistance exercise or both on the musculoskeletal function of older individuals with these three conditions.

Methods/analysis

Studies will be selected from electronic databases, including PubMed/MEDLINE, EMBASE, Scopus, Web of Science and the Cochrane Library, without restrictions on language or publication date. The outcomes evaluated will include muscle mass, muscle strength, BMD and physical performance after combined interventions of MPS and physical exercise of any type. The risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to classify the certainty of the evidence into four levels: high, moderate, low and very low. Meta-analysis will be performed given the homogeneity of the studies, using random effects methods in the face of the expected heterogeneity. The standardised mean difference (SMD) will be used for continuous data, and the I² index will assess heterogeneity (I² > 50%). Sensitivity analysis, ‘leave one out’ and a strategy for dealing with missing data will be carried out. Statistical analysis will be conducted using the STATA 18 software with a 95% CI and p

Ethics and dissemination

Formal ethical approval will not be required as primary data collection will not be performed. The results will be disseminated through peer-reviewed publications and presentations at conferences dedicated to the relevant field of study.

PROSPERO registration number

CRD42024555933.

Diverse diagnostic and management approaches for acute rheumatic fever in Australia and New Zealand: findings of a prospective clinical study

Por: Peiris · R. · Webb · R. · Bennett · J. · Yan · J. · Francis · J. R. · Remenyi · B. · Chan Mow · F. · Burgess · R. · Wilson · N. J. · Stanley · A. · Francis · L. · Holloway · R. · Westbury · R. · Lawrence · S. · Hernandez-Gomez · Y. · Broadhurst · D. · Moreland · N. J. · McGregor · R. · Mot
Objectives

To describe diagnostic and management characteristics of acute rheumatic fever (ARF) among participants in the ‘Searching for a Technology-Driven Acute Rheumatic Fever Test’ study, in order to answer clinical questions and determine epidemiological and practice differences in different settings.

Design

Multisite, prospective cohort study.

Setting

One hospital in northern Australia and two hospitals in New Zealand, 2018–2021.

Participants

143 episodes of definite, probable or possible ARF among 141 participants (median age 10 years, range 5–23; 98% Indigenous).

Primary and secondary outcome measures

Participant characteristics, clinical, biochemical and echocardiographic data were explored using descriptive data. Associations with length of stay were determined using multivariable regression analysis.

Results

ARF presentations were heterogeneous with the most common ARF ‘phenotype’ in 19% of cases being carditis with joint manifestations (polyarthritis, monarthritis or polyarthralgia), fever and PR prolongation. The total proportion of children with carditis was 61%. Australian compared with New Zealand participants more commonly had ARF recurrence (22% vs 0%), underlying RHD (48% vs 0%), possible/probable ARF (23% vs 9%) and were underweight (64% vs 16%). Erythrocyte sedimentation rate (ESR) provided an incremental diagnostic yield of 21% compared with C reactive protein. No instances of RHD were diagnosed among participants in New Zealand. Positive throat Group A Streptococcus culture was more common in New Zealand than in Australian participants (69% vs 3%). Children often required prolonged hospitalisation, with median hospital length-of-stay being 7 days (range 2–66). Significant predictors for length of stay in a multivariable regression model were valve disease (adjusted OR (aOR) 1.56, 95% CI 1.23 to 1.98, p

Conclusions

This study provides new knowledge on ARF characteristics and management and highlights international variation in diagnostic and management practice. Differing approaches need to be aligned. Meanwhile, locally specific information can help guide patient expectations after ARF diagnosis.

Impact of a community-based asynchronous review clinic on appointment attendance delays across an eye hospital network in London, UK: an interrupted time series analysis

Por: Ndwandwe · S. · Fu · D. J. · Adesanya · J. · Bazo-Alvarez · J. C. · Ramsay · A. I. G. · Fulop · N. J. · Magnusson · J. · Napier · S. · Cammack · J. · Baker · H. · Kumpunen · S. · Alarcon Garavito · G. A. · Elphinstone · H. · Mills · G. · Scully · P. · Symons · A. · Webster · P. · Wilson
Objective

To assess the impact of opening a large community-based asynchronous review ophthalmic clinic on attendance delays among patients with stable chronic eye disease attending a London teaching eye hospital network.

Design

Interrupted time-series analysis of routine electronic health records of appointment attendances.

Setting

A large eye hospital network with facilities across London, UK, between June 2018 and April 2023.

Participants

We analysed 69 257 attendances from 39 357 patients, with glaucoma and medical retina accounting for 62% (n=42 982) and 38% (n=26 275) of visits, respectively. Patients over 65 made up 54% (n=37 824) of attendances, while 53% (n=37 014) were from the more deprived half of the population, and 51% (n=35 048) were males.

Intervention

An asynchronous review clinic opened in a shopping centre in London, in autumn 2021, following the COVID-19 lockdown in spring 2020.

Main outcome measures

Average attendance delays (days), calculated as the difference between follow-up attendance date and the latest clinically appropriate date determined at the preceding attendance.

Results

Pre-COVID-19, attendance delays for chronic eye disease monitoring were increasing by 0.9 days per week (95% CI, 0.8 to 0.9) on average, worsening to 2.0 days per week (95% CI, 2.0 to 2.0) after the first COVID-19 national lockdown, mid-March 2020. Opening the asynchronous review clinic increased appointment capacity, with delays decreasing on average by 8.1 days per week (95% CI, 8.1 to 8.2) shortly after opening. The rate of decrease slowed to 0.3 days per week (95% CI, 0.3 to 0.3) after 5 months. We found no significant differences in average attendance delays by age, gender or level of deprivation.

Conclusion

The asynchronous review clinic significantly reduced attendance delays across the hospital network, addressing pre-existing backlog for stable chronic eye diseases. The reduction appeared to be maintained after the initial backlog had been cleared.

Developing and studying an outcome-focused measure of mental healthcare quality based on patient-reported symptoms in the USA: a study protocol

Por: Young · A. S. · Cai · L. · Jackson · N. J. · Leung · L. B. · Thames · A. D.
Introduction

Various psychological, cognitive, behavioural, medication and neurostimulation treatments can improve the outcomes of people with depressive and anxiety disorders. However, in usual practice, there is large variability in treatment delivery and treatments are poorly characterised. The effectiveness and quality of mental health services in the community are not accurately monitored and are poorly understood. At present, healthcare organisations, payers and policy makers know little about the quality of care they support. Similarly, patients and families have limited information on quality to guide choice of provider or organisation. It will be necessary to implement monitoring of treatment quality so that treatment and outcomes can be improved. This study develops, tests and validates a new, transdiagnostic outcome-focused mental health quality measure. This measure is based on routine, regular patient reports of their symptoms. It is designed to be aggregated at the provider, clinic, organisation or plan level; inform choice of provider; and be used to improve routine delivery of services and quality of care among patients with common psychiatric disorders.

Methods and analysis

The project analyses existing data with responses to a wide variety of items that are known to assess depression or anxiety and empirically selects symptom items for a transdiagnostic outcome-focused quality measure. The project informs risk adjustment and benchmarking of the quality measure by studying how patient, provider and practice factors, including health-related social needs, baseline symptom severity and diagnoses, affect outcomes. Drawing on these, the project specifies an outcome-focused quality measure that includes risk adjustment and benchmarks for improvement; and studies, at practices nationally, its feasibility and psychometric properties, the effect of treatment characteristics on the quality of care, and the effect of quality on health-related quality of life.

Ethics and dissemination

Results will be published. The quality measure is designed to be broadly relevant across community settings and populations and to be submitted for endorsement by regulatory and governing bodies.

Scoping review of guidance on safe non-consultant medical staffing recommendations for UK acute hospitals

Por: Gower · H. · Doran · N. J. · Hamza · N. · Smith · S.
Objectives

Modern healthcare is delivered by an increasingly multidisciplinary team, complicating workforce management. Patient safety inquiries have led to reports such as the Francis and Berwick reports (2013), which consistently emphasise the need for proper staffing to ensure patient safety. While nursing has seen progress with safe staffing guidelines, there remains a significant gap in guidance for medical staff. In the UK, consultants are the senior members of the medical profession who have achieved a Certification of Completion of Training (CCT) and are able to practice independently. The number of required consultants is based on population needs, and future consultant numbers are used to determine the number of doctor training positions. However, this approach often overlooks the specific staffing needs of individual hospitals, particularly regarding patient safety. Although a named consultant is responsible for patient care, the medical workforce that handles day-to-day operations in acute hospitals consists of a diverse group of staff who require varying degrees of supervision based on their competency and seniority. This group includes medical associates, such as physician associates, and resident doctors (formerly known as junior doctors) who themselves are a heterogeneous group needing different levels of oversight. As a result, the previous focus solely on consultant staffing requirements must be broadened to address the realities of patient care. At present, no single resource provides a comprehensive summary of staffing recommendations that includes all groups within the non-consultant medical workforce. This research aims to identify existing guidance for this part of the medical workforce to support healthcare management. The objectives of this study are, therefore, to identify guidance and recommendations for safe staffing levels from a patient safety perspective for non-consultant medical staff in UK acute hospitals.

Design

A scoping literature review was conducted and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Data sources

This used five search strategies: internal website searches, Google Scholar searches, general Google searches, medical database searches via Ovid and a snowballing strategy.

Eligibility criteria

English-language resources published from 2015 to 2024 that provide specific guidance on safe medical staffing levels for National Health Service acute hospitals in the UK.

Data extraction and synthesis

Thematic analysis was employed to identify patterns in the diverse guidance discovered, using a hybrid approach that combined human and AI methods. The benefits and limitations of this method are discussed.

Results

The review yielded 10 703 resources, of which 10 met all eligibility criteria for analysis. Identified themes include staffing requirements, staffing recommendations and a tiered system approach.

Conclusions

Medical staffing is complex due to the varying roles and competencies involved. While some guidance exists, there is a clear need for more comprehensive recommendations that go beyond specific specialities. Future research should focus on developing a medical safe staffing tool and addressing the barriers to comprehensive guidance, both of which would enhance patient care.

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