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Fluoxetine and fractures after stroke: an individual patient data meta-analysis of three large randomised controlled trials of fluoxetine for stroke recovery
Get PDFBackground
Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimised in randomised controlled trials (RCTs).
Aim
Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin score (mRS) at six months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20mg for six months) for stroke recovery.
Methods
We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis) and context, then performed multivariable analyses to explore independent predictors of fractures. We explored whether the trend towards a poorer mRS at 6 months was explained by a fracture excess. Risk of bias was assessed using GRADE.
Results
Among 5907 patients randomised at a mean of 6.6 days (SD3.6) post-stroke onset and followed for six months, the number with fractures at 6 months was 93 (3.15%) in the fluoxetine group vs 41 (1.39%) in the control group (difference 1.76%, 95% CI 0.10 to 2.51%). 128 patients with fractures were suitable for further analyses. Of these 102 (80%) were in sites typically affected by osteoporosis; 115 (90%) were associated with falls and one (1%) with a seizure. Independent fracture risk factors were female sex (hazard ratio (HR) 1.96; 95% CI 1.37 to 2.81, p=0.0002), age>70 years (HR 2.30, 95% CI 1.52 to 3.49, p<0.001), previous fractures (HR 0.63 for no previous fractures, 95% CI 0.42 to 0.94, p=0.0227), and randomised treatment (fluoxetine) (HR 2.39; 95% CI 1.64 to 3.49, p<0.001). The common odds ratio for the effect of fluoxetine on mRS at 6 months was unchanged after excluding fracture patients. Risk of bias was high for imprecision.
Conclusion
Fractures were more common in the fluoxetine group but the absolute risk of fractures was small and risk estimates were imprecise. Most fractures occurred with a fall, and in osteoporotic locations. Fractures did not modify the effect of fluoxetine on functional outcome
Integrating biochemical and functional assessments in equine joint research: A study of gait asymmetry and synovial fluid biomarkers
No full textInjection of recombinant interleukin-1β (reIL-1β) is commonly used in equine joint research to evaluate the clinical and biological outcomes of inflammation, often tracking changes over time to assess the effects of the experimental model. Incorporating functional assessments, such as gait asymmetry analysis, in conjunction with biological assessments, is essential for capturing the real-world impact of joint interventions and ensuring findings translate to meaningful improvements in equine health and locomotion. This study aimed to examine the relationship between synovial fluid biochemical changes and symmetry analysis (inertial measurement unit; IMU) following a 75-ng injection of recombinant interleukin-1β (reIL-1β) into the left intercarpal joint of 11 horses Synovial fluid samples were collected at 0 h (pre-injection; control) and at 6 h and 12 h post-injection and analyzed for prostaglandin E2 (PGE2), glycosaminoglycan (GAG), nitric oxide (NO), chondroitin sulfate epitope 846 (CS846), and resolvin D1 (RvD1). The IMU data were collected at baseline (hour 0) and 6 and 12 h post-injection to assess poll and pelvic movement during in-hand trot trials, with MinDiff (loading asymmetry) and MaxDiff (push-off asymmetry) values calculated. A linear mixed model was used to assess the association between biochemical outcomes and asymmetry measures with significance set at P ≤ 0.05. Increased synovial PGE2 significantly contributed to greater poll MinDiff (estimate = 0.007, SE = 0.003, P = 0.006), whereas elevated CS846 was a key contributor to increased poll MaxDiff (estimate = 0.006, SE = 0.003, P = 0.036). Additionally, higher PGE2 was linked to lower pelvis MaxDiff (estimate = −0.002, SE = 0.001, P = 0.024), whereas increased CS846 was associated with higher pelvis MinDiff (estimate = 0.003, SE = 0.001, P = 0.026). This research emphasizes the value of integrating biochemical and functional data to provide a more comprehensive tool for evaluating interventions for joint health
The PREPARED Code: A Global Code of Conduct for Research During Pandemics
Get PDFThis chapter presents the 27 articles of the PREPARED Code: A Global Code of Conduct for Research during Pandemics. Illustrative diagrams capture essential features of its development (e.g. the geographical distribution of the authors) and structure (e.g. that it is built around fairness, respect, care and honesty)
Simple and cost-effective liver retraction technique for laparoscopic right adrenalectomy – An initial experience from a tertiary care centre
Get PDFLiver retraction is a critical step for optimal surgical exposure and preventing liver injury during right laparoscopic adrenalectomy (LA), due to the complex relationship of the suprarenal gland with the inferior vena cava and liver. Current retraction methods require specialised instruments like Nathanson and robotic retractors, which are challenging to procure in developing countries due to limited funding and resources. To overcome these challenges, we propose a technique for liver retraction using locally available basic laparoscopic tools, making LA more feasible in resource-limited settings. The patient was laid in the reverse Trendelenburg position and then laterally rotated to the left. Port 1, port 2 and port 3 were placed in a triangular configuration with the camera lying in situ in port 2, while ports 1 and 3 serve as working ports. Port 4 was made in the epigastrium, and a Maryland forceps or laparoscopic needle holder was introduced beneath the right liver lobe, supporting the liver uniformly. This surgical technique is characterised by its simplicity, feasibility and cost-effectiveness. It ensures reliable liver retraction while providing ergonomic benefits for surgeons and upholding both surgical safety and operational efficiency
674 The Use of MAKO CT-Based Robotic-Assisted System for Total Knee Arthroplasty Compared to Conventional Total Knee Arthroplasty: A Systematic Review
No full textAim
This study aims to investigate the differences between the MAKO CT-based robotic-assisted system and the conventional technique for TKA, focusing on assessing patient outcomes, surgical time and costs.
Background
Total knee arthroplasty (TKA) is a surgical procedure that replaces a damaged knee joint. The conventional method involves surgically removing the damaged knee joint and replacing it with an implant. In contrast, the MAKO system TKA is an amalgamation of robotic surgery with a CT-based 3D model of the patient’s knee.
Method
A PRISMA systematic review was conducted using 4 databases (Cochrane, Google Scholar, OVID and Pubmed) to identify all studies that reported the use and results of the CT-based robotic-assisted system to perform TKA. The outcome criteria investigated included patient-reported scores, implant alignment, analgesia requirements, estimated blood loss, surgical time, operation time, tourniquet time, implant thickness variations, and length of hospital stay.
Results
141 studies were identified, of which 17 met the inclusion criteria. Of those, 13 were included in this study. The MAKO CT-based robotic-assisted system, compared to conventional methods for TKA, resulted in similar patient outcomes, higher implant precision, lower analgesia requirements, lower blood loss, longer operation time, longer tourniquet time, lower implant thickness, and shorter hospital stays. Due to several factors, the cost of the MAKO CT-based robotic-assisted system for TKA could be less than that of conventional TKA.
Conclusions
The MAKO CT-based robotic-assisted system for TKA does not lead to different patient outcomes but should be considered in practice in light of other supporting parameters improving surgical care
Exosome Therapy for Hair Loss
Get PDFHair loss is a widespread condition impacting millions globally, often causing considerable psychological and social stress. Traditional treatments like minoxidil and finasteride face challenges due to variable effectiveness and possible side effects, leading to an interest in innovative regenerative therapies. Exosomes, tiny extracellular vesicles released
by diverse cell types, have gained attention for their role in cell communication and their capacity to influence critical biological processes, like inflammation and cell growth. This review delves into the use of exosomes for treating hair loss, elaborating on their mechanisms, such as activating hair follicle stem cells, fostering angiogenesis, decreasing
inflammation, and reducing oxidative stress. Findings from both preclinical and clinical research underline their potential to improve hair density, thickness, and scalp condition, with few negative side effects. The review also touches on obstacles like exosome isolation standardization, scalability, and long-term safety, proposing potential solutions, including advancements in exosome engineering and combination therapies. Looking ahead, there's an emphasis on the necessity for extensive clinical trials and the integration of exosome therapy with other regenerative approaches. This treatment showcases a cutting-edge, minimally invasive method with incredible potential to transform hair loss management loss
Periodicals and Belonging?
Get PDFThis article explores the notion of belonging in periodical studies, arguing that periodicals have historically functioned as spaces for negotiating and performing belonging. Amid contemporary political rhetoric about borders and belonging, we examine how periodicals have both constructed and contested boundaries of inclusion and exclusion. Drawing on interdisciplinary frameworks from political geography, psychology, and cultural studies, we propose that belonging operates through periodicals in multiple dimensions: material (through physical production, layout, and tactile engagement), temporal (connecting past, present, and imagined futures), spatial (creating real and imagined communities across geographical boundaries), and affective (generating emotional attachments thatbind readers together). The special issue presents six articles examining how periodicals foster belonging in institutional and professional communities (regimental journals and film criticism); place-based belonging; activism and resistance (revolutionary soldier newspapers and alternative magazines for marginalized groups). Together, these studies reveal how periodicals simultaneously challenge and reinforce boundaries of inclusion, offering valuable insights into contemporary challenges of polarization and fragmentation in our contemporary sociopolitical landscape
British Society of Gastroenterology guidelines on inflammatory bowel disease in adults: 2025
Get PDFIn response to recent advancements in inflammatory bowel disease (IBD) management, the British Society of Gastroenterology (BSG) Clinical Services and Standards Committee (CSSC) has commissioned the BSG IBD section to update its guidelines, last revised in 2019. These updated guidelines aim to complement the IBD standards and promote the use of the national primary care diagnostic pathway for lower gastrointestinal symptoms to enhance diagnostic accuracy and timeliness. Formulated through a systematic and transparent process, this document reflects a consensus of best practices based on current evidence. The guideline, while developed primarily for the UK, is structured to support IBD management internationally. It is endorsed by the BSG executive board and CSSC without external commercial funding, with involvement primarily supported through professional roles in public institutions and the National Health Service (NHS). Methodological revisions since the prior guidelines have enhanced rigor in technical review and development, with methodology details published independently following peer review. In developing the recommendations, 89 clinical experts and stakeholders participated in an online survey, identifying primary outcomes, such as clinical and endoscopic remission, as well as adverse event metrics, all stratified by clinically relevant effect sizes. These guidelines are intended to support clinical decision-making but are not prescriptive, recognizing that individual clinical scenarios may warrant tailored approaches. Further research may inform future revisions as new evidence emerges
Cognitive behavioural therapy in comparison to treatment as usual in young adults at high risk of developing bipolar disorder (Bipolar At Risk): a randomised controlled trial to investigate the efficacy of a treatment approach targeted at key appraisal change: Bipolar At Risk Trial II (BART II)
Get PDFBackground: Research has demonstrated the ability to identify and treat individuals at high risk of developing psychosis. It is possible to use a similar strategy to identify people who have an emergent risk of bipolar disorder (BD). Interventions during the early phase may improve outcomes and reduce risk of transition. Criteria have been established to identify individuals considered to be at high risk for developing BD, also known as Bipolar At Risk (BAR). Offering a psychological intervention may provide the possibility of prevention. Evaluating efficacy and the mechanisms by which this treatment works is now required. Methods: A multicentre, rater-masked randomised controlled trial with two parallel arms will compare cognitive behaviour therapy (CBT) for young people meeting BAR criteria (CBTBAR) + Treatment as Usual (TAU) vs. TAU alone. Participants will be recruited from five National Health Service (NHS) sites in the UK. Outcome and mediational variables will be collected at baseline, 17-weeks (in treatment), 27-weeks (post-CBTBAR /TAU), and 52-weeks. Qualitative work will examine the perceived mechanisms of change and implementation of CBTBAR in the NHS. Discussion: Our efficacy hypotheses are CBTBAR + TAU (compared to TAU alone) will lead to improvement in mood swings, a reduction in the likelihood of transition to BD, and improvements to functioning and quality of life. Our mechanistic hypothesis is CBTBAR + TAU causes improvement in mood swings due to the reduction of extreme positive and negative appraisals of internal states which in turn improves subsequent behaviours used to control mood and then internal states. Our trial will explore the perceived mechanism of change via this novel intervention (CBTBAR) and if the approach can be implemented within current services in the UK. Trial registration/Status: The trial protocol is registered with ISRCTN (ISRCTN13363197, registered on 25th January 2023). Recruitment started in February 2023 and is ongoing