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How long is the arm immobilised after a conservatively managed displaced proximal humerus fracture and does early mobilisation effect complication rates: A systematic reviewBackground: Conservative management of displaced proximal humerus fractures involves a period of rest in a sling followed by physiotherapy. The aim of this review is to provide a narrative synthesis of how long immobilisation is used, types of slings, when and how exercises are introduced, and if complications may be associated with these components. Method: A systematic search of the literature was undertaken. Two researchers screened relevant articles using Covidence software, with a third reviewer consulted for consensus. Data was extracted and a narrative synthesis is presented. Results: Thirty-nine studies were included (3059 studies screened, 159 full-text reviews). This included a cohort of 2664 patients with a mean age of 70.9. Time immobilised in sling ranged from 1 to 6 weeks. Sling types were variable and were grouped into low, medium and higher levels of support. Exercises were introduced at variable timescales tending to introduce passive and pendular exercises first. Complications were reported in 243 incidences (9.1%). Discussion: There was vast variation in how long patients were immobilised for, types of slings used and when and how exercises were introduced and progressed. No relationship was found between complications and these components. Research to identify the most effective approach is required.
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The effectiveness of lifestyle interventions in heart failure with preserved ejection fraction: a systematic review and network meta-analysisAims: To perform a network meta-analysis to determine the effectiveness of lifestyle interventions on exercise tolerance and quality of life (QoL) in people with HFpEF. Methods: Ten databases were searched for randomised controlled trials that evaluated a diet and/or exercise intervention in people with HFpEF up until May 2022. The co-primary outcomes were peak oxygen uptake (V̇O2peak) and QoL as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). We synthesised data using network meta-analysis. Results: Thirteen trials were identified including a total of 869 participants and incorporated six different interventions. Improvements in V̇O2peak compared to controls were seen for all exercise interventions (2.88 [95%CI: 1.36; 4.39]ml/kg/min) for high intensity interval training (HIIT); 2.37 [95%CI: 1.02; 3.71] ml/kg/min for low intensity exercise (LIT) combined with a hypocaloric diet; 2.05 [95%CI: 0.81; 3.29]ml/kg/min for moderate intensity continuous training (MICT); 1.94 [95%CI: 0.59; 3.29] ml/kg/min for LIT; 1.85 [95%CI: 0.27; 3.44]ml/kg/min for MICT combined with resistance training) but not a hypocaloric diet alone (1.26 [95%CI: -0.08; 2.61]ml/kg/min). Only HIIT (-14.45 [95%CI: -24.81; -4.10] points) and LIT (95%CI: -11.05 [-20.55; -1.54] ml/kg/min) significantly improved MLHFQ score. Network meta-analysis indicated HIIT was the most effective intervention for improving both V̇O2peak (mean improvement 2.88 [95%CI: 1.36; 4.39]ml/kg/min, follow up (FU) range 4 weeks- 3 years) and QoL (-14.45 [95%CI: -24.81; -4.10] points, FU range 12-26 weeks) compared to usual care. Conclusions: This network meta-analysis indicates that HIIT is the most effective lifestyle intervention studied to improve exercise capacity and QoL with mean improvements exceeding the minimum clinically meaningful thresholds. HIIT is likely to be an underused management strategy in HFpEF, but further studies are needed to confirm long-term improvements in symptoms and clinical outcomes.
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A scoping review of artificial intelligence in medical education: BEME Guide No. 84Background: Artificial Intelligence (AI) is rapidly transforming healthcare, and there is a critical need for a nuanced understanding of how AI is reshaping teaching, learning, and educational practice in medical education. This review aimed to map the literature regarding AI applications in medical education, core areas of findings, potential candidates for formal systematic review and gaps for future research. Methods: This rapid scoping review, conducted over 16 weeks, employed Arksey and O'Malley's framework and adhered to STORIES and BEME guidelines. A systematic and comprehensive search across PubMed/MEDLINE, EMBASE, and MedEdPublish was conducted without date or language restrictions. Publications included in the review spanned undergraduate, graduate, and continuing medical education, encompassing both original studies and perspective pieces. Data were charted by multiple author pairs and synthesized into various thematic maps and charts, ensuring a broad and detailed representation of the current landscape. Results: The review synthesized 278 publications, with a majority (68%) from North American and European regions. The studies covered diverse AI applications in medical education, such as AI for admissions, teaching, assessment, and clinical reasoning. The review highlighted AI's varied roles, from augmenting traditional educational methods to introducing innovative practices, and underscores the urgent need for ethical guidelines in AI's application in medical education. Conclusion: The current literature has been charted. The findings underscore the need for ongoing research to explore uncharted areas and address potential risks associated with AI use in medical education. This work serves as a foundational resource for educators, policymakers, and researchers in navigating AI's evolving role in medical education. A framework to support future high utility reporting is proposed, the FACETS framework.
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Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK studyDuring the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.
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Hamstring muscle injuries in athleticsHamstring muscle injuries (HMI) are a common and recurrent issue in the sport of athletics, particularly in sprinting and jumping disciplines. This review summarizes the latest literature on hamstring muscle injuries in athletics from a clinical perspective. The considerable heterogeneity in injury definitions and reporting methodologies among studies still needs to be addressed for greater clarity. Expert teams have recently developed evidence-based muscle injury classification systems whose application could guide clinical decision-making; however, no system has been adopted universally in clinical practice, yet.The most common risk factor for HMI is a previously sustained injury, particularly early after return-to-sport. Other modifiable (e.g. weakness of thigh muscles, high-speed running exposure) and non-modifiable (e.g. older age) risk factors have limited evidence linking them to injury. Reducing injury may be achieved through exercise-based programs, but their specific components and their practical applicability remain unclear.Post-injury management follows similar recommendations to other soft tissue injuries, with a graded progression through stages of rehabilitation to full return to training and then competition, based on symptoms and clinical signs to guide the individual speed of the recovery journey. Evidence favoring surgical repair is conflicting and limited to specific injury sub-types (e.g. proximal avulsions). Further research is needed on specific rehabilitation components and progression criteria, where more individualized approaches could address the high rates of recurrent HMI. Prognostically, a combination of physical examination and magnetic resonance imaging (MRI) seems superior to imaging alone when predicting 'recovery duration,' particularly at the individual level.
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Late-onset mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and the role of serial imagingMitochondria are essential for human metabolic function. Over 350 genetic mutations are associated with mitochondrial diseases, which are inherited in a matrilineal fashion. In mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), defective mitochondrial function and resultant impaired cellular energy production compromise vascular perfusion in affected tissues. Early diagnostic criteria suggested the diagnosis should be considered in those under 40. However, a broader range of phenotypes are now recognised, including those that present for the first time later in life. The primary presenting feature in MELAS is a stroke-like episode invariably resulting in patients undergoing neuroradiological imaging. We present a case of a woman with a first presentation of a stroke-like episode and seizures in her 40s who was eventually diagnosed with MELAS. We detail her clinical presentation, treatment and diagnosis, emphasising the role of serial imaging in her diagnosis.
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Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heartCongenital heart disease (CHD) is the most common congenital anomaly, with an overall incidence of approximately 1% in the United Kingdom. Exome sequencing in large CHD cohorts has been performed to provide insights into the genetic aetiology of CHD. This includes a study of 1891 probands by our group in collaboration with others, which identified three novel genes-CDK13, PRKD1, and CHD4, in patients with syndromic CHD. PRKD1 encodes a serine/threonine protein kinase, which is important in a variety of fundamental cellular functions. Individuals with a heterozygous mutation in PRKD1 may have facial dysmorphism, ectodermal dysplasia and may have CHDs such as pulmonary stenosis, atrioventricular septal defects, coarctation of the aorta and bicuspid aortic valve. To obtain a greater appreciation for the role that this essential protein kinase plays in cardiogenesis and CHD, we have analysed a Prkd1 transgenic mouse model (Prkd1em1 ) carrying deletion of exon 2, causing loss of function. High-resolution episcopic microscopy affords detailed morphological 3D analysis of the developing heart and provides evidence for an essential role of Prkd1 in both normal cardiac development and CHD. We show that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects, and bicuspid aortic and pulmonary valves, and is lethal. Even in heterozygotes, cardiac differences occur. However, given that 97% of Prkd1 heterozygous mice display normal heart development, it is likely that one normal allele is sufficient, with the defects seen most likely to represent sporadic events. Moreover, mRNA and protein expression levels were investigated by RT-qPCR and western immunoblotting, respectively. A significant reduction in Prkd1 mRNA levels was seen in homozygotes, but not heterozygotes, compared to WT littermates. While a trend towards lower PRKD1 protein expression was seen in the heterozygotes, the difference was only significant in the homozygotes. There was no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT-qPCR. Overall, we demonstrate a vital role of Prkd1 in heart development and the aetiology of CHD.
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The indignities of shielding during the COVID-19 pandemic for people with sickle cell disorders: an interpretative phenomenological analysisThis article seeks to understand the first-hand experiences of people with sickle cell, a recessively inherited blood disorder, who were identified as clinically extremely vulnerable during the COVID-19 pandemic. Part of a larger sequential mixed-methods study, this article uses a selective sample of eight qualitative semi-structured interviews, which were analysed using interpretative phenomenological analysis (IPA). The first stage of IPA focused on practical concerns participants had correlated to understanding shielding and their feelings about being identified as clinically extremely vulnerable. In a secondary stage of analysis, we examined the emotions that it brought forth and the foundations of those based on discriminations. This article adds to our theoretical understanding of embodiment and temporality with respect to chronicity and early ageing. It explains how people with sickle cell disorders have an embodied ethics of crisis and expertise. It also elucidates how people's experiences during the pandemic cannot be seen in void but illustrates ableism, racism, and ageism in society writ large.
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Prevalence and clinical significance of electrocardiographic complete right bundle branch block in young individualsBackground and aims: There is limited information on the clinical significance of complete right bundle branch block (CRBBB) in young individuals. The aim of this study was to determine the prevalence and significance of CRBBB in a large cohort of young individuals aged 14-35 years old. Methods: From 2008 to 2018, 104,369 consecutive individuals underwent a cardiovascular assessment with a health questionnaire, electrocardiogram, clinical consultation, and selective echocardiography. Follow-up was obtained via direct telephone consultations. Mean follow-up was 7.3 ± 2.7 years. Results: CRBBB was identified in 154 (0.1%) individuals and was more prevalent in males compared with females (0.20% vs. 0.06%; p<0.05) and in athletes compared with non-athletes (0.25% vs. 0.14%; p<0.05). CRBBB-related cardiac conditions were identified in 7 (5%) individuals (4 with atrial septal defect, 1 with Brugada syndrome, 1 with progressive cardiac conduction disease and 1 with atrial fibrillation). Pathology was more frequently identified in individuals with non-isolated CRBBB compared with individuals with isolated CRBBB (14% vs 1%; p < 0.05) and in individuals with a QRS duration of ≥130 milliseconds (ms) compared with individuals with a QRS of <130ms (10% vs 1%; p<0.05). Conclusion: The prevalence of CRBBB in young individuals was 0.1% and was more prevalent in males and athletes. CRBBB-related conditions were identified in 5% of individuals and were more common in individuals with non-isolated CRBBB and more pronounced intraventricular conduction delay (QRS duration of ≥130ms). Secondary evaluation should be considered for young individuals with CRBBB with symptoms, concerning family history, additional electrocardiographic anomalies or significant QRS prolongation (≥130ms).
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Technological innovations to improve patient engagement in nephrologyTechnological innovation has accelerated exponentially over the last 2 decades. From the rise of smartphones and social media in the early 2000s to the mainstream accessibility of artificial intelligence (AI) in 2023, digital advancements have transformed the way we live and work. These innovations have permeated health care, covering a spectrum of applications from virtual reality training platforms to AI-powered clinical decision support tools. In this review, we explore fascinating recent innovations that have and can facilitate patient engagement in nephrology. These include integrated care mobile applications, wearable health monitoring tools, virtual/augmented reality consultation and education platforms, AI-powered appointment booking systems, and patient information tools. We also discuss potential pitfalls in implementation and paradigms to adopt that may protect patients from unintended consequences of being cared for in a digitalized health care system.
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Evidence for molecular subtyping in pancreatic ductal adenocarcinoma: a systematic reviewBackground: Pancreatic Ductal Adenocarcinoma (PDAC) patients exhibit varied responses to multimodal therapy. RNA gene sequencing has unravelled distinct tumour biology subtypes, forming the focus of this review exploring its impact on survival outcomes. Methods: A systematic search across PubMed, Medline, Embase, and CINAHL databases targeted studies assessing long-term overall and disease-free survival in PDAC patients with molecular subtyping. Results: Fifteen studies including 2731 patients were identified. Molecular subtyping was performed by RNA sequencing and Immunohistochemistry in 14 studies and by Mass Spectrometry in 1 study. Two main tumour subtypes were identified (classical and basal-like or squamous) with basal like associated with poorer outcomes. Further subtypes were identified in individual studies. Superior survival was seen with classical subtype in all other analyses that compared the classical and basal subtypes. High risk stromal subtypes were identified on further analysis of the stroma and were associated with a worse survival independent of the tumour subtype. Conclusion: Molecular subtyping of PDAC specimens can identify patients with high-risk tumour biology and poor survival outcomes. Routine subtyping is limited by the cost of RNA sequencing and the volume of raw data generated which has made its translation into routine clinical practice difficult.
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Long-term treatment with rilzabrutinib in patients with immune thrombocytopeniammune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87×109/L in all patients, 68×109/L in those who had rilzabrutinib monotherapy (n=5), and 156×109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n=11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 (69%) patients continued to receive rilzabrutinib. A platelet count of ≥50×109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts ≥30×109/L and ≥50×109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106×109/L at 3-6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals. This trial is registered at www.clinicaltrials.gov NCT03395210 and https://www.clinicaltrialsregister.eu EudraCT 2017-004012-19.
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Oral cavity cancers: ethnic differences in radiotherapy outcomes in a majority South Asian Leicester communityAims: Squamous cell carcinoma oral cavity cancers (SCCOCCs) have a higher reported incidence in South Asian countries. We sought to compare presenting stage and outcome by ethnicity in patients with SCCOCC treated with radical radiotherapy in a single centre in the UK. Materials and methods: All patients with SCCOCC treated with radical radiotherapy at an oncology department in Leicester (UK) between 2011 and 2017 were identified. Baseline demographic, clinical data and 2-year treatment outcomes were reported. Results: Of the 109 patients included, 40 were South Asian and 59 were non-South Asian. South Asians had significantly poorer 2-year disease-free survival compared with non-South Asians (54.6% versus 73%, P = 0.01). Conclusion: Our analysis suggests that South Asians with SCCOCC have poorer outcomes despite a younger age and similar disease characteristics. Environmental, social factors and differing biology of disease may be responsible and further research is required to inform targeted interventions.
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Early and mid-term outcomes after aortic valve replacement using a novel tissue bioprosthesis: a systematic reviewObjectives: While current data show a clear trend towards the use of bioprosthetic valves during aortic valve replacement (AVR), durability of bioprosthetic valves remains the most important concern. We conducted a 1st systematic review of all available evidence that analysed early and mid-term outcomes after AVR using the Inspiris RESILIA™ bioprosthesis. Methods: A systematic literature search was performed to identify all relevant studies evaluating early and mid-term outcomes after AVR using the Inspiris RESILIA bioprosthesis and including at least 20 patients with no restriction on the publication date. Subgroup meta-analysis was performed to compare Inspiris RESILIA and PERIMOUNT Magna Ease bioprosthesis and to pool the early postoperative mortality and stroke rates. Results: A total of 416 studies were identified, of which 15 studies met the eligibility criteria. The studies included a total of 3202 patients with an average follow-up of up to 5.3 years. The average age of patients across the studies was 52.2-75.1 years. Isolated AVR was performed in 39.0-86.4% of patients. In-hospital or 30-day postoperative mortality was 0-2.8%. At the mid-term follow-up, freedom from all-cause mortality was up to 85.4%. Among studies with mid-term follow-up, trace/mild paravalvular leak was detected in 0-3.0%, while major paravalvular leak was found only in up to 2.0% of patients. No statistically significant differences in terms of mortality (P = 0.98, odds ratio 1.02, 95% confidence interval 0.36-2.83) and stroke (P = 0.98, odds ratio 1.01, 95% confidence interval 0.38-2.73) between the Inspiris RESILIA bioprosthesis and PERIMOUNT Magna Ease bioprosthesis were observed in the subgroup meta-analysis. Conclusions: Mid-term data on the safety and haemodynamic performance of the novel aortic bioprosthesis are encouraging. Further comparative studies with other bioprostheses and longer follow-up are still required to endorse durability and safety of the novel bioprosthesis.
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Use of autogenous fascia lata slings in the surgical correction of ptosis: A systematic review of the literature and meta-analysisPtosis is an abnormally low-positioned upper eyelid. Management depends on severity, aetiology, and function of the levator palpebrae superioris muscle (LPS). This review evaluates the success of autogenous fascia lata slings (AFLS) in the surgical management of ptosis, together with complication and reoperation/revision rates. A literature search was conducted on PubMed, Google Scholar PROSPERO, Dynamed, DARE, EMBASE, Cochrane, and BMJ databases (PROSPERO registration: CRD42023475090), and 30 studies (3690 patients and 5059 eyes) were included. The average age of the patients was 14.2 years with a ratio of male:female patients of 1:0.7. A total of 2532 eyes had undergone a fascial sling with autogenous fascia lata. The average follow-up period was 32.6 months. Improvement in the margin to reflex distance 1 (MRD1) with fascial sling surgery was 2.79 mm. The rate of complications from surgery involving autogenous fascia lata was 21.3%. The most common complications included lagophthalmos (19.8%), residual ptosis (11.5%), and corneal damage (10.4%). The reoperation rate was 13.4%. Most common indications for reoperation were cosmetic, with asymmetry (18%), lid crease abnormalities (30%), and upper eyelid trimming (18%). The overall complication rate in AFLS patients was 20% (95% CI: 6 to 35, p < 0.01; I2 = 89%) versus 27% (95% CI: 14 to 40, p < 0.01; I2 = 90%) in non-AFLS patients. AFLSs are prudent in the surgical management of ptosis. The results of this review demonstrate that their use is associated with similar complication rates but fewer reoperations than other traditional techniques.
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Practical guide on left atrial appendage closure for the non-implanting physician. An international consensus paperA significant proportion of patients who suffer from atrial fibrillation and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well-known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with atrial fibrillation. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.
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A multicomponent intervention to reduce daily sitting time in office workers: the SMART Work & Life three-arm cluster RCTBackground: Office workers spend 70-85% of their time at work sitting. High levels of sitting have been linked to poor physiological and psychological health. Evidence shows the need for fully powered randomised controlled trials, with long-term follow-up, to test the effectiveness of interventions to reduce sitting time. Objective: Our objective was to test the clinical effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable workstation, compared with usual practice at 12-month follow-up. Design: A three-arm cluster randomised controlled trial. Setting: Councils in England. Participants: Office workers. Intervention: SMART Work & Life is a multicomponent intervention that includes behaviour change strategies, delivered by workplace champions. Clusters were randomised to (1) the SMART Work & Life intervention, (2) the SMART Work & Life intervention with a height-adjustable workstation (i.e. SMART Work & Life plus desk) or (3) a control group (i.e. usual practice). Outcome measures were assessed at baseline and at 3 and 12 months. Main outcome measures: The primary outcome was device-assessed daily sitting time compared with usual practice at 12 months. Secondary outcomes included sitting, standing, stepping time, physical activity, adiposity, blood pressure, biochemical measures, musculoskeletal issues, psychosocial variables, work-related health, diet and sleep. Cost-effectiveness and process evaluation data were collected. Results: A total of 78 clusters (756 participants) were randomised [control, 26 clusters (n = 267); SMART Work & Life only, 27 clusters (n = 249); SMART Work & Life plus desk, 25 clusters (n = 240)]. At 12 months, significant differences between groups were found in daily sitting time, with participants in the SMART Work & Life-only and SMART Work & Life plus desk arms sitting 22.2 minutes per day (97.5% confidence interval -38.8 to -5.7 minutes/day; p = 0.003) and 63.7 minutes per day (97.5% confidence interval -80.0 to -47.4 minutes/day; p < 0.001), respectively, less than the control group. Participants in the SMART Work & Life plus desk arm sat 41.7 minutes per day (95% confidence interval -56.3 to -27.0 minutes/day; p < 0.001) less than participants in the SMART Work & Life-only arm. Sitting time was largely replaced by standing time, and changes in daily behaviour were driven by changes during work hours on workdays. Behaviour changes observed at 12 months were similar to 3 months. At 12 months, small improvements were seen for stress, well-being and vigour in both intervention groups, and for pain in the lower extremity and social norms in the SMART Work & Life plus desk group. Results from the process evaluation supported these findings, with participants reporting feeling more energised, alert, focused and productive. The process evaluation also showed that participants viewed the intervention positively; however, the extent of engagement varied across clusters. The average cost of SMART Work & Life only and SMART Work & Life plus desk was £80.59 and £228.31 per participant, respectively. Within trial, SMART Work & Life only had an incremental cost-effectiveness ratio of £12,091 per quality-adjusted life-year, with SMART Work & Life plus desk being dominated. Over a lifetime, SMART Work & Life only and SMART Work & Life plus desk had incremental cost-effectiveness ratios of £4985 and £13,378 per quality-adjusted life-year, respectively. Limitations: The study was carried out in one sector, limiting generalisability. Conclusions: The SMART Work & Life intervention, provided with and without a height-adjustable workstation, was successful in changing sitting time. Future work: There is a need for longer-term follow-up, as well as follow-up within different organisations. Trial registration: Current Controlled Trials ISRCTN11618007.