The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis:Design and rationale

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.Trial registration: ClinicalTrials.gov Identifier: NCT05946044.</p

Barriers and enablers to the implementation of the 6-PACK falls prevention program: A preimplementation study in hospitals participating in a cluster randomised controlled trial

Evidence for effective falls prevention interventions in acute wards is limited. One reason for this may be suboptimal program implementation. This study aimed to identify perceived barriers and enablers of the implementation of the 6-PACK falls prevention program to inform the implementation in a randomised controlled trial. Strategies to optimise successful implementation of 6-PACK were also sought. A mixed-methods approach was applied in 24 acute wards from 6 Australian hospitals. Participants were nurses working on participating wards and senior hospital staff including Nurse Unit Managers; senior physicians; Directors of Nursing; and senior personnel involved in quality and safety or falls prevention. Information on barriers and enablers of 6-PACK implementation was obtained through surveys, focus groups and interviews. Questions reflected the COM-B framework that includes three behaviour change constructs of: capability, opportunity and motivation. Focus group and interview data were analysed thematically, and survey data descriptively. The survey response rate was 60% (420/702), and 12 focus groups (n = 96 nurses) and 24 interviews with senior staff were conducted. Capability barriers included beliefs that falls could not be prevented; and limited knowledge on falls prevention in patients with complex care needs (e.g. cognitive impairment). Capability enablers included education and training, particularly face to face case study based approaches. Lack of resources was identified as an opportunity barrier. Leadership, champions and using data to drive practice change were recognised as opportunity enablers. Motivation barriers included complacency and lack of ownership in falls prevention efforts. Motivation enablers included senior staff articulating clear goals and a commitment to falls prevention; and use of reminders, audits and feedback. The information gained from this study suggests that regular practical face-to-face education and training for nurses; provision of equipment; audit, reminders and feedback; leadership and champions; and the provision of falls data is key to successful falls prevention program implementation in acute hospitals

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Picropodophyllin induces G2/M cell cycle arrest and inhibits downstream signaling and function of IGF-IR.

<p>A, Cell cycle analysis by propidium iodide staining of brain-seeking cells (231Br and BT474 Br3) treated with 1 µg/mL PPP for 48 hr. B, Immunoblot of phospho-proteins activation downstream of IGF-IR in brain-seeking cells treated with escalating concentrations of PPP for 24h. C, Transwell migration assay of 231Br cells treated with 1 µg/mL PPP for 24 hr. D, Quantitative analysis of relative number of migrating cells from (C). E, Matrigel invasion assay of 231Br cells treated with 1 µg/mL PPP for 24 hr. F, Quantitative analysis of relative number of migrating cells from (E). All migration and invasion assays used complete medium as a chemoattractant. Bars represent mean ± SEM.</p