UNASSIGNED: Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person\'s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations.Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation.
UNASSIGNED: The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics.
UNASSIGNED: The iFraP trial will answer important questions about the effectiveness of the new \'iFraP\' osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines.
UNASSIGNED: 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407.
Background: For people with osteoporosis, broken bones (called ‘fragility fractures’) can occur from low or no trauma and cause significant disability. Medicines can strengthen bone and lower the chance of fragility fractures. However, many people who experience a fragility fracture do not start or continue taking osteoporosis medicines. People commonly choose not to take osteoporosis medicines because they are unsure what medicines are for, confused about fracture ‘risk’ and/or worried about side-effects. To address this, we developed the ‘iFraP intervention’: 1. The iFraP ‘decision-support tool’: to support patients and healthcare professionals talk together to make decisions about medicines2. iFraP training for healthcare professionals to:a. use the tool in appointments with patientsb. give understandable, clear and consistent information c. listen to and address patient concerns This trial investigates whether the iFraP intervention makes decision-making about osteoporosis medicines easier, and whether it is cost-effective, acceptable and practical to deliver. Methods: 380 patients will take part who will be 50 years and older and referred to a fracture prevention service, because they have broken a bone. Patients taking part will be allocated to receive either a usual NHS appointment or an appointment using the iFraP intervention. Patients will complete a questionnaire before their appointment, and 2 weeks and 3 months afterwards. Some patients will be asked if they consent to have their appointment recorded and/or be interviewed, to understand how the decision-support tool is being used, and patient’s views of the iFraP intervention. Outputs: If successful, the iFraP intervention will benefit patients and the NHS by helping patients make decisions about osteoporosis medicine. If the iFraP intervention increases the number of people with osteoporosis that start and continue taking osteoporosis medicines, iFraP will lower the number of future fractures, and reduce the negative outcomes that result from fractures (e.g. significant disability).

OBJECTIVE: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.
METHODS: Phase III double blind randomised controlled trial.
METHODS: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic.
METHODS: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG.
METHODS: Randomised 1:1 using a web-based procedure to receive a single 0.1mL intradermal dose of BCG-Denmark (BCG group, n=1999) or saline (placebo group, n=1989).
METHODS: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12-months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion).
RESULTS: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6% to 24.5%) compared with the placebo group (19.6%; 95%CI 17.6% to 21.5%); adjusted difference +3.0 percentage points (95%CI 0.2% to 5.8%; p=0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95%CI 9.5% to 12.4%) compared with 9.6% in the placebo group (95%CI 8.3% to 11.1%); adjusted difference +1.3 percentage points (95%CI -0.7% to 3.3%, p=0.2). Breakthrough COVID-19 (post COVID-19 vaccination), and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95%CI 0.60 to 4.02, p=0.4) and two deaths due to COVID-19, both in the placebo group.
CONCLUSIONS: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among health care workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19.
BACKGROUND: ClinicalTrials.gov NCT04327206.

BACKGROUND: There is a critical global shortage of nurses in mental health, with workforce attrition due in large part to workplace stressors. Proactive strengths-based interventions to strengthen nurses\' capacity to manage stress and improve mental health, wellbeing and resilience may also support workforce retention.
OBJECTIVE: To determine the effects of a resilience-building programme on mental health nurses\' coping self-efficacy (primary outcome), and psychological distress, wellbeing, resilience, posttraumatic growth, emotional intelligence behaviours, workplace belonging, and turnover intention (secondary outcomes).
METHODS: Partially clustered randomised controlled trial.
METHODS: Large tertiary metropolitan mental health service in Australia.
METHODS: A total of 144 registered and enrolled nurses working clinically ≥0.6 full-time equivalent (73/intervention, 71/control), with 122 completing 3-month follow-up.
METHODS: The Promoting Resilience in Nurses programme is an evidence-based workplace intervention delivered by trained facilitators across two workshops. Surveys were administered online upon registration and prior to randomisation (Time 1) into Intervention or Control (no intervention) arms, and immediately after the final workshop (Time 2), and at three months follow-up (Time 3). Linear mixed models for outcome measures were fitted to Time 2 and 3 responses.
RESULTS: There were seven intervention groups, with seven to 13 participants per group. Coping self-efficacy improved at Time 2 (estimated intervention effect 21.2 units, 95 % Confidence Intervals: 13.3 to 29.0) and Time 3 (12.1 units, 4.7 to 19.6), as well as wellbeing (Time 2: 9.2 units, 5.0 to 13.4), resilience (Time 2: 0.24 units, 0.01 to 0.46) and posttraumatic growth (Time 2: 16.1 units, 7.0 to 25.3). Psychological distress reduced (Time 2: -3.7 units, -6.2 to -1.31). All were sustained at three months. Emotional intelligence behaviours were improved (Time 2: 3.5 units, 0.6 to 6.5) but not sustained. Workplace belonging improved at Time 3 (0.34 units, 0.02 to 0.65) only. No statistically significant effects for turnover intention.
CONCLUSIONS: Despite major contextual challenges, the Promoting Resilience in Nurses programme achieved the aims of promoting nurses\' efficacy to cope with stress and regulate their emotions and improving mental health and wellbeing. The findings support the programme as a feasible and successful intervention for nurses across other settings and contexts.
BACKGROUND: Australian New Zealand Clinical Trials Registry (ACTRN12620001052921). Registered 15/10/2020. First recruitment 04/02/2021.
CONCLUSIONS: Promoting Resilience in Nurses intervention improved coping self-efficacy, wellbeing, resilience, posttraumatic growth, emotional intelligence and psychological distress.

BACKGROUND: The Phosphoinositide 3-kinase (PI3K) inhibitors may be used in cancer progression and mortality along with standard therapy to improve therapeutic efficacy of Advanced Breast Cancer (ABC).
OBJECTIVE: This systematic review and meta- analysis were conducted to understand the therapeutic and toxicity profile of PI3K inhibitors in ABC.
METHODS: The electronic databases were searched for suitable trials as per the criteria. The outcomes assessed were Progression- Free Survival, Objective Response Rate and Disease Control Rate. The data were systematically reviewed and meta-analyzed by Mantele- Haenszel method.
RESULTS: Seven studies were included in the systematic review and meta- analysis. The co- administration of PI3K inhibitors with standard therapy improved the Progression- Free Survival significantly, while a marginal improvement was observed in Objective Response Rate, no difference in Disease Control Rate and toxicity significantly increased.
CONCLUSIONS: The addition of PI3K inhibitors decreased the risk of progression but increased the risk of toxicity.

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BACKGROUND: Poverty, HIV and perinatal depression represent a triple threat to public health in sub-Saharan Africa because of their combined negative effects on parenting and child development. In the resource-constrained context of low-income and middle-income countries, a lay-counsellor-delivered intervention that combines a psychological and parenting intervention could offer the potential to mitigate the consequences of perinatal depression while also optimising scarce resources for healthcare.Measuring the cost-effectiveness of such a novel intervention will help decision-makers to better understand the relative costs and effects associated with replicating the intervention, thereby supporting evidence-based decision-making. This protocol sets out the methodological framework for analysing the cost-effectiveness of a cluster randomised controlled trial (RCT) that compares a combined intervention to enhanced standard of care when treating depressed, HIV-positive pregnant women and their infants in rural South Africa.
METHODS: This cost-effectiveness analysis (CEA) protocol complies with the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. A societal perspective will be chosen.The proposed methods will determine the cost and efficiency of implementing the intervention as per the randomised control trial protocol, as well as the cost of replicating the intervention in a non-research setting. The costs will be calculated using an appropriately adjusted version of the Standardised Early Childhood Development Costing Tool.Primary health outcomes will be used in combination with costs to determine the cost per improvement in maternal perinatal depression at 12 months postnatal and the cost per improvement in child cognitive development at 24 months of age. To facilitate priority setting, the incremental cost-effectiveness ratios for improvements in child cognitive development will be ranked against six other child cognitive-development interventions according to Verguet et al\'s methodology (2022).A combination of activity-based and ingredient-based costing approaches will be used to identify, measure and value activities and inputs for all alternatives. Outcomes data will be sourced from the RCT team.
BACKGROUND: The University of Oxford is the sponsor of the CEA. Ethics approval has been obtained from the Human Sciences Research Council (HSRC, #REC 5/23/08/17), South Africa and the Oxford Tropical Research Ethics Committee (OxTREC #31-17), UK.Consent for publication is not applicable since no participant data are used in this protocol.We plan to disseminate the CEA results to key policymakers and researchers in the form of a policy brief, meetings and academic papers.
UNASSIGNED: ISRCTN registry #11 284 870 (14/11/2017) and SANCTR DOH-27-102020-9097 (17/11/2017).

The present study aimed to determine whether a remotely delivered intervention, based on an individual case management, can reduce falls and their consequences in community-dwelling older people with a history of multiple falls. In this randomized controlled trial, 32 participants were randomized to the intervention group, which comprised a 16-week case management program involving a multidimensional assessment, targeted interventions according to the identified fall risk factors, and development of individualized care plans. The intervention was performed by trained gerontologists, under weekly supervision of professionals with experience in falls. The control group (n = 30) received usual care. Falls were monitored over 12 months with monthly falls calendars and telephone calls. Remotely delivered case management presented an 82 % uptake of recommendations. There was a trend toward a reduced fall incidence in the intervention vs control group, with lower fall, fall injury and fracture rates in the intervention group compared with the control group at both the 16-week and 12-month time-points, with the difference statistically significant for injurious fall rates at 12 months - IRR=0.18 (95 % CI = 0.04 to 0.74).

OBJECTIVE: To assess the added value of caregiver-mediated exercises combined with telerehabilitation in addition to usual care compared to usual care alone on the self-reported mobility outcome after subacute stroke.
METHODS: Multicentre, observer-blinded, parallel randomised controlled trial. An off-site researcher allocated treatments using minimisation.
METHODS: Four rehabilitation centres in the Netherlands.
METHODS: Forty-one patient-caregiver dyads within 3 months poststroke.
METHODS: Eight-week blended care program with caregiver-mediated mobility exercises for 2.5 h per week supported by telerehabilitation and four face-to-face sessions in addition to usual care.
METHODS: Self-reported mobility domain of the Stroke Impact Scale postintervention. Secondary outcomes were functional outcome, dyads\' psychosocial wellbeing, care transition to the community postintervention and after 6 months.
RESULTS: Forty-one dyads (21 intervention, 20 control) were randomised, and 37 (N = 18; N = 19) were analysed following intention-to-treat. The Stroke Impact Scale mobility was not significantly different between groups postintervention (B 0.8, 95% CI -6.8-8.5, p = 0.826). The secondary outcomes, namely, (a) caregivers\' quality of life postintervention (p = 0.013), (b) caregivers\' symptoms of depression postintervention (p = 0.025), and (c) independence in leisurely activities at 6 months (p = 0.024), showed significant benefits in favour of caregiver-mediated exercises with telerehabilitation. A significant difference favouring controls was found in self-reported muscle strength at 6 months (p = 0.002).
CONCLUSIONS: Caregiver-mediated exercises combined with telerehabilitation yielded no differential effect on our primary outcome self-reported mobility. Although the trial is underpowered, current findings are in line with previous trials. Future studies should further explore beneficial effects of caregiver involvement in stroke rehabilitation targeting psychosocial wellbeing.

BACKGROUND: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional \'step-up\' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis.
METHODS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure.
BACKGROUND: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences.
BACKGROUND: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.

UNASSIGNED: The Tranexamic acid for IntraCerebral Haemorrhage-2 (TICH-2) trial reported no significant improvement in death and dependency at day 90 despite reductions in haematoma expansion, early neurological deterioration and early death. However, significant recovery after stroke, particularly intracerebral haemorrhage (ICH), may take more than 3 months. Here we report the participant outcomes at 1 year after stroke.
UNASSIGNED: TICH-2 was a prospective randomised controlled trial that tested the efficacy and safety of tranexamic acid in spontaneous ICH when given within 8 h of onset. Patients with ICH on anticoagulation were excluded. Centralised blinded telephone follow up was performed for patients from the United Kingdom at 1 year. The primary outcome was modified Rankin Scale at 1 year. Secondary outcomes included Barthel index, Telephone Interview Cognitive Status-modified, EuroQoL-5D and Zung Depression Scale. This was a prespecified secondary analysis of the TICH-2 trial.
UNASSIGNED: About 2325 patients were recruited into the trial (age 68.9 ± 13.8 years; 1301 male, 56%). About 1910 participants (82.2%) were eligible for day 365 follow up. 57 patients (3.0%) were lost to follow up. Tranexamic acid did not reduce the risk of poor functional outcome at 1 year (adjusted OR 0.91 95% CI 0.77-1.09; p = 0.302). However, Cox proportional hazard analysis revealed significant survival benefit in the tranexamic acid group (adjusted HR 0.83, 95% CI 0.70-0.99; p = 0.038).
UNASSIGNED: There was no difference in functional outcome at 1 year after ICH. Tranexamic acid may reduce mortality at 1 year without an increase in severely dependent survivors. But this should be interpreted with caution as this is a result of secondary analysis in a neutral trial.