Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Immunisation is one of the most valuable, impactful and cost-effective public health interventions which delivers positive health, social and economic benefits. Globally, 4 million deaths worldwide are prevented by childhood vaccination every year. In Ethiopia, despite huge progress being made, the routine immunisation coverage has never reached the targeted figures and planned goals. Pastoralist communities are often disproportionately under-vaccinated, and there is often a confluence of interrelated factors that drive this outcome. This study enables us to identify factors affecting immunisation service utilisation in the pastoralist communities of Ethiopia, which helps to design effective and context-specific interventions.

This study aims to explore the behavioural and social drivers (BeSDs) of routine immunisation among the communities with high numbers of zero-dose and under-immunised children in Afar, Somali and Gambella regions of Ethiopia.

A qualitative exploratory study was conducted in three selected regions of Ethiopia (Gambella, Somali and Afar) from 9 November 2023 to 30 December 2023. Purposive sampling was used. A total of 33 interviews were conducted in the three regions. Sample size was determined based on idea saturation. Data was collected using interview guides. The interview guide was developed after reviewing relevant literature, desk review and using the journey to health and immunisation framework. A separate interview guide was developed for the journey mapping exercise, in-depth interview, healthcare workers discussion guide, focus group discussion and observation. Data was analysed thematically.

Behavioural (lack of awareness, lack of reminder/forgetting, misperception about vaccines, negative previous experience, lost card and fear of post-vaccination adverse events).

Structural (language barrier, long distance from home to facility, high cost of transportation, long waiting time, limited training of healthcare professionals and incentives, inconvenient service hours, shortage of health professionals, disrespect by the healthcare provider), Socio-cultural (competing priorities, low community engagement, lack of decision-making autonomy, limited husband involvement, workload, rural residence and larger family size were the commonly mentioned barriers to routine immunisation uptake. On the other hand, structural (house to house visit by health extension workers, counselling about adverse events, presence of outreach service, affordability (free of charge)), behavioural and socio-cultural (knowledge of adverse event management, and respect from community) were enablers to routine immunisation service uptake in pastoralist communities.

The study found several individual and contextual factors affecting routine immunisation uptake in pastoralist communities. Context-specific and tailored interventions which address zero dose drivers should be designed so as to enhance vaccine uptake. The findings suggested the need to design context-specific interventions to address the aforementioned barriers to immunisation.

Outcome measures used in sciatica research lack standardisation, making it difficult to combine data for analysis. This scoping review identified and categorised Patient Reported Outcome Measures (PROMs) employed in randomised controlled trials investigating sciatica interventions, providing a foundation for developing a consensus-based core outcome set.

Scoping review.

A systematic search was conducted across MEDLINE, Embase and Cochrane Central for research published between 1999 and 2024.

We included randomised controlled trials that involved patients with sciatica and used at least one PROM.

Screening and data extraction were performed independently by at least two reviewers. PROMs were categorised using the OMERACT Filter 2.0 framework, inductively sub-categorised into domains, and then the frequency was counted to identify patterns of use. Collection time points and intervention type were also assessed.

187 studies met the inclusion criteria. These studies employed 69 different PROMs, collected 548 times across all papers. The Visual Analogue Scale for pain (n=115), Oswestry Disability Index (n=109) and Numeric Pain Rating Scale (n=74) were most frequently used. PROMs predominantly addressed the pathophysiological (n=274) and life impact (n=262) domains, with minimal attention to resource use/economic impact (n=12). Injection-based interventions were the most studied treatment approach. Follow-up periods using the same PROMs varied considerably between studies, with trends by intervention type.

This review identified and categorised PROMs from numerous research studies, revealing substantial heterogeneity in outcome measurement for sciatica trials. This demonstrates the need for a standardised core outcome set. The predominance of use of non-sciatica-specific pain and disability measures suggests potential gaps in capturing sciatica-specific outcomes. Inconsistent follow-up durations and administration methods further highlight the requirement for standardisation.

Over 777 million COVID-19 infections have occurred globally, with data suggesting that 10%–20% of those infected develop Long COVID. Fatigue is one of the most common and disabling symptoms of Long COVID. We aim to assess the feasibility and safety of a new, remotely delivered, multimodal rehabilitation intervention, paced to prevent post-exertional malaise (PEM), to support the conduct of a future, definitive randomised trial.

We will conduct a randomised, two-arm feasibility trial (COVIDEx intervention vs usual care). Sixty participants with Long COVID will be recruited and randomised prior to giving informed consent under a modified Zelen design using 1:1 allocation with random permuted blocks via central randomisation to receive either the COVIDEx intervention or usual care. The 50-minute, remotely delivered, COVIDEx intervention will occur twice weekly for 8 weeks. All participants will wear a non-invasive device throughout their entire study participation, to track heart rate, blood oxygen saturation, steps, sleep and monitor PEM. The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness. Secondary objectives will include refined estimates for the standard deviation and correlation between baseline and follow-up measurements of fatigue. Feasibility and clinical outcomes will be collected at baseline, 4, 8, 12 and 24 weeks. Qualitative interviews with participants and physiotherapists will explore intervention acceptability and barriers/facilitators.

Ethical approval for this study was obtained by the Western University Health Sciences Research Ethics Board (REB# 123902). Dissemination plans include sharing of trial findings at conferences and through open access publications and patient/community channels.

NCT06156176

Community paramedicine services (CPSs) may alleviate the increasing pressure on emergency medical services (EMSs) but lack the capacity for patient transport. The study aims to determine whether a municipality implementing the CPS between periods (CPS_REGION) compared with a control municipality (CTR_REGION) served by EMS only affected patient flow and safety in a rural Norwegian setting.

A quasi-experimental study evaluating patient flow and safety before and after the introduction of CPS in one of two rural municipalities.

Two rural Norwegian municipalities that were served by EMS from nearby municipalities before the study started.

Before and after the introduction of CPS, a total of 604 and 650 patients, respectively, were included in CPS_REGION, and 367 and 408 patients, respectively, in CTR_REGION.

CPS was introduced in CPS_REGION between the two data collection periods, whereas CTR_REGION continued to be served by EMS.

The outcome of patient flow was assessed by the number of admissions to nearby hospitals, the number of patient contacts and the location for delivery and treatment. The outcome for safety was assessed as the need for medical recontact within 7 days and 30-day mortality.

Hospital admission rates increased over the two study periods, being insignificant in CPS_REGION (+4.7%, p=0.373) and significant in CTR_REGION (+23.2%, p

Introducing CPS resulted in fewer hospital admissions, with more patients being treated locally. No safety concerns with respect to medical recontacts and 30-day mortality were observed. We conclude that CPS can alter patient flow towards more local treatment without compromising safety.

Distal radius fractures are the most common fractures seen in the emergency department in children in the USA. However, no established or standardised guidelines exist for the optimal management of completely displaced fractures in younger children. The proposed multicentre randomised trial will compare functional outcomes between children treated with fracture reduction under sedation versus children treated with simple immobilisation.

Participants aged 4–10 years presenting to the emergency department with 100% dorsally translated metaphyseal fractures of the radius less than 5 cm from the distal radial physis will be recruited for the study. Those patients with open fractures, other ipsilateral arm fractures (excluding ulna), pathologic fractures, bone diseases, or neuromuscular or metabolic conditions will be excluded. Participants who agree to enrol in the trial will be randomly assigned via a minimal sufficient balance algorithm to either sedated reduction or in situ immobilisation. A sample size of 167 participants per arm will provide at least 90% power to detect a difference in the primary outcome of Patient-Reported Outcomes Measurement Information System Upper Extremity computer adaptive test scores of 4 points at 1 year from treatment. Primary analyses will employ a linear mixed model to estimate the treatment effect at 1 year. Secondary outcomes include additional measures of perceived pain, complications, radiographic angulation, satisfaction and additional procedures (revisions, refractures, reductions and reoperations).

Ethical approval was obtained from the following local Institutional Review Boards: Advarra, serving as the single Institutional Review Board, approved the study (Pro00062090) in April 2022. The Hospital for Sick Children (Toronto, ON, Canada) did not rely on Advarra and received separate approval from their local Research Ethics Board (REB; REB number: 1000079992) on 19 July 2023. Results will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings.

NCT05131685.

Despite the important role of healthcare services in trauma recovery, many survivors of violence do not seek help. This study aims to examine rates of healthcare utilisation, including differences for physical violence versus rape, gender and physical injury (vs no injury) and obstacles to seeking care within 6 months following incidents of physical violence and rape.

The participants were randomly chosen from the National Population Registry in Norway and invited to participate in a telephone survey on violence exposure and health between June 2021 and June 2022 (N=4299, 49% women).

The sample included 1768 violence-exposed individuals. Of the women (n=749), 82.1% had experienced physical violence and 40.3% had experienced forcible rape. Of the men, most had experienced physical violence (98.6%) and a small percentage had experienced rape (3.5%).

Logistic regression models were used to investigate whether healthcare seeking differed by gender, type of violence (rape vs physical violence) and severity (physical injury). Barriers to accessing healthcare were also investigated using descriptive statistics and content analysis.

Healthcare seeking rates were low after rape (16.9%) and physical violence (24.2%), with somewhat higher rates among individuals experiencing both types of violence (39.9%). There were no statistically significant differences in the odds of healthcare utilisation between the three types of violence exposures when we controlled for gender, physical injury, violence characteristics and sociodemographic factors. Men were more likely than women to have sought healthcare (adjusted OR (aOR): 1.37, 95% CI: 1.02 to 1.85, p=0.042). Physical injury was strongly associated with greater healthcare utilisation (aOR: 6.39, 95% CI: 4.85 to 8.41, p

Few victims seek healthcare shortly after experiencing rape or physical violence. Quantitative and qualitative findings indicate that many seek healthcare exclusively for severe physical injury. These results emphasise the need to improve health services’ outreach to victims of violence, who are at heightened risk of mental health issues and chronic illnesses.

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.

CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.

The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).

NCT05614349

Preoperative exercise training is recommended, when feasible, for people undergoing resection for lung cancer and has been shown to reduce the risk of postoperative pulmonary complications and improve preoperative exercise capacity. However, preoperative exercise training programmes are not commonly available in the Australian clinical practice setting due to a range of factors including resource and time restrictions. We aim to describe the protocol to evaluate the implementation of an existing preoperative exercise training programme in people undergoing lung cancer resection in an Australian setting.

This is an evaluation of a secondary objective of a study examining the effect of lung cancer resection on exercise capacity, lung function and symptoms of dyspnoea and quality of life. Participants will be prospectively recruited at the time of lung cancer diagnosis and planned surgical treatment through the lung cancer multidisciplinary team of a metropolitan hospital in Sydney, Australia. All participants will be offered the choice of participating in the preoperative exercise training programme which encompasses a hybrid gym and telerehabilitation programme of up to five sessions/week from baseline until surgical date. The programme will be evaluated using the Reach, Effectiveness, Adoption, Implementation, Maintenance Framework including both quantitative and qualitative measures which will be analysed using descriptive statistics and qualitative analysis coded inductively.

The study has received ethical approval through the Northern Sydney Local Health District reference 2023/ETH01643 and has been registered prospectively. Findings will be disseminated through peer-reviewed publication and scientific conference presentation.

ACTRN12624000359538.

To describe current levels of interest and action around decarbonisation in general practice settings, and awareness and use of currently available materials designed to support general practice teams undertake decarbonisation activity.

Cross-sectional, mixed methods, online survey.

473 general practices in three Integrated Care Board regions in England.

Multiprofessional general practice staff.

There were 328 responses from 163 (34.5%) practices. Most respondents were general practitioner (GP) partners (98; 29.9%), other clinical staff (93; 28.3%) or managerial staff (76; 23.2%). 229 (69.8%) respondents felt that acting to reduce carbon emissions from primary care is a legitimate part of general practice activity. However, only 44 (13.4%) felt that there is sufficient training and resources to support such activity, and only 59 (18.0%) agreed that there was sufficient leadership from higher levels within the health service to enable this. 58 (35.6%) practices had a lead for sustainability, generally managerial staff (22; 37.9%) or GP partners (17; 29.3%). Compared to other practices, those with a decarbonisation lead reported increased levels of decarbonisation actions currently being undertaken (mean = 5.2 vs 3.1; t(161) = 7.7, p2=31.9, p2=32.3, p

This survey provides insight into how English general practices and their staff regard decarbonisation activities. The findings highlight the importance of leadership, resources and incentives in driving such activities and have implications for initiatives to help achieve wider decarbonisation goals in healthcare.

To determine how high performing is defined in relation to a health system and chart the literature on the definitions and key concepts of high-performing healthcare systems.

Scoping review.

MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to July 2024. The grey literature was also searched.

Included studies reported on health systems and high performance to identify explicit definitions, research outcomes and knowledge gaps.

Two reviewers independently screened 5721 citations and 507 full-text articles, resulting in the inclusion of 35 primary articles and 47 companion documents in the review. Three independent definitions for a high-performance health system were identified. 24 research studies reported outcomes on the elements of a high-performing health system (58%), system evaluation (32%) and tool development or validation (10%). Knowledge gaps identified were the lack of a common definition, a lack of common indicators, strategies for moving evidence into policy and practice, and difficulties with comparisons across health systems.

We found limited definitions and a lack of empirical evidence on our topic. There is an opportunity for primary research in the area of health systems and high performance.