Staged bilateral total knee arthroplasty: does history dictate the future?

A retrospective cohort study of 668 staged bilateral TKA patients was conducted to determine first-side versus second-side subjective and objective outcomes. Improvement in patient perceived function, measured by one-year Oxford Score (OKS) was defined by a minimal clinically important difference of >5 points in OKS. Results indicate that patients who had a minimal clinically important improvement (MCII) on the first-side have a significantly greater chance of maintaining or improving benefit with second-side TKA (OR 3.2; 95% CI 1.63-6.22; P=0.000). Of those with no clinical improvement (NCI), 71.4% achieved MCII on the second-side, while 28.6% remained NCI (P=0.000). Patients who do not initially benefit from first-side TKA should not be denied second-side staged-TKA as they still have a significant chance of achieving an MCII.

Health programmes and services addressing the prevention and management of infectious diseases in people who inject drugs in Canada: a systematic integrative review.

OBJECTIVES: People who inject drugs (PWID) experience a high burden of injection drug use-related infectious disease and challenges in accessing adequate care. This study sought to identify programmes and services in Canada addressing the prevention and management of infectious disease in PWID. DESIGN: This study employed a systematic integrative review methodology. Electronic databases (PubMed, CINAHL and Web of Science Core Collection) and relevant websites were searched for literature published between 2008 and 2019 (last search date was 6 June 2019). Eligible articles and documents were required to address injection or intravenous drug use and health programmes or services relating to the prevention or management of infectious diseases in Canada. RESULTS: This study identified 1607 unique articles and 97 were included in this study. The health programmes and services identified included testing and management of HIV and hepatitis C virus (n=27), supervised injection facilities (n=19), medication treatment for opioid use disorder (n=12), integrated infectious disease and addiction programmes (n=10), needle exchange programmes (n=9), harm reduction strategies broadly (n=6), mobile care initiatives (n=5), peer-delivered services (n=3), management of IDU-related bacterial infections (n=2) and others (n=4). Key implications for policy, practice and future research were identified based on the results of the included studies, which include addressing individual and systemic factors that impede care, furthering evaluation of programmes and the need to provide comprehensive care to PWID, involving medical care, social support and harm reduction. CONCLUSIONS: These results demonstrate the need for expanded services across a variety of settings and populations. Our study emphasises the importance of addressing social and structural factors that impede infectious disease care for PWID. Further research is needed to improve evaluation of health programmes and services and contextual factors surrounding accessing services or returning to care. PROSPERO REGISTRATION NUMBER: CRD42020142947.

Health programmes and services addressing the prevention and management of infectious diseases in persons who inject drugs in Canada: a systematic integrative review protocol.

INTRODUCTION: Injection drug use (IDU) and intravenous drug use (IVDU) are of concern to the people using drugs, their families and health systems. One of the complications of IDU/IVDU is the risk of infection. Clinical experience has shown that persons who inject drugs (PWID) are hospitalised and re-hospitalised frequently. In Canada there are sparse data about the reasons for which PWID are admitted to hospital and their health trajectories, especially for infectious diseases. There are special concerns regarding PWID with infections who leave the hospital against medical advice and those who leave with a peripherally inserted central catheter line in place for administration of long-term antibiotics or other therapies. Improving our understanding of current programmes and services addressing the prevention and management of infectious diseases and their complications in PWID could lead to focused interventions to enhance care in this population. METHODS AND ANALYSIS: An integrative systematic review allows for inclusion of a variety of methodologies to understand a health issue from different viewpoints. PubMed, CINAHL, Web of Science Databases and websites of the Public Health Agency of Canada, Canadian Institute for Substance Use Research, and Canadian Centre on Substance Use and Addiction will be searched using terms for infectious diseases, drug use and geography (Canada) and limited to the last 10 years (2009-2019). The Quality Appraisal Tool in Studies with Diverse Designs will be used to appraise the quality of identified studies and documents. Quantitative, qualitative or mixed methods data synthesis will be used as needed. ETHICS AND DISSEMINATION: This study is a secondary analysis of publicly available documents; therefore, no ethics approval is required. This information will inform a research agenda to further investigate interventions that aim to address these issues. PROSPERO REGISTRATION NUMBER: CRD42020142947.

Feasibility and implementation of a healthy lifestyles program in a community setting in Ontario, Canada: protocol for a pragmatic mixed methods pilot study.

INTRODUCTION: Rates of chronic conditions, such as diabetes, cardiovascular disease and obesity are increasing in Canada and internationally. There are effective lifestyle interventions that are known to improve chronic conditions. However, there is often a gap in 'how to' make lifestyle changes. Mental health and other determinants of health play a role in the development and progression of chronic conditions. Changing habits takes time and requires the use of multiple techniques, including mental health and behavioural change strategies, based on a person's needs. A new, multidisciplinary, person-centred and evidence-based and practice-based programme has been created to address these needs. This proposal aims to evaluate the feasibility and implementation of this programme and to determine changes in participant-directed and clinical outcomes through a pilot study. METHODS AND ANALYSIS: A pragmatic mixed methods design will be used to study multiple dimensions of the year-long healthy lifestyles programme. The pilot study includes a randomised controlled trial, with 30 participants randomised to either the programme or to a comparator arm, and qualitative components to determine the feasibility of the programme, including recruitment and retention, data missing rates and resources needed to run this programme. Changes in participant-directed and clinical outcomes will be measured. Descriptive statistics, t-tests and repeated measures analysis of variance (ANOVA) for within group comparisons and generalised estimating equations for between group analyses will be used. Qualitative interviews of programme staff and healthcare providers and family focus groups will be used to further enhance the findings and improve the programme. ETHICS AND DISSEMINATION: Approval from the Hamilton Integrated Research Ethics Board (HiREB) has been obtained. Informed consent will be obtained prior to enrolling any participant into the study. Participant IDs will be used during data collection and entry. Peer-reviewed publications and presentations will target researchers, health professionals and stakeholders. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03258138.HiREB project number: 3793.

Microtubule-dependent subcellular redistribution of the transcriptional coactivator p/CIP.

The transcriptional coactivator p/CIP is a member of a family of nuclear receptor coactivator/steroid receptor coactivator (NCoA/SRC) proteins that mediate the transcriptional activities of nuclear hormone receptors. We have found that p/CIP is predominantly cytoplasmic in a large proportion of cells in various tissues of the developing mouse and in a number of established cell lines. In mouse embryonic fibroblasts, serum deprivation results in the redistribution of p/CIP to the cytoplasmic compartment and stimulation with growth factors or tumor-promoting phorbol esters promotes p/CIP shuttling into the nucleus. Cytoplasmic accumulation of p/CIP is also cell cycle dependent, occurring predominantly during the S and late M phases. Leptomycin B (LMB) treatment results in a marked nuclear accumulation, suggesting that p/CIP undergoes dynamic nuclear export as well as import. We have identified a strong nuclear import signal in the N terminus of p/CIP and two leucine-rich motifs in the C terminus that resemble CRM-1-dependent nuclear export sequences. When fused to green fluorescent protein, the nuclear export sequence region is cytoplasmic and is retained in the nucleus in an LMB-dependent manner. Disruption of the leucine-rich motifs prevents cytoplasmic accumulation. Furthermore, we demonstrate that cytoplasmic p/CIP associates with tubulin and that an intact microtubule network is required for intracellular shuttling of p/CIP. Immunoaffinity purification of p/CIP from nuclear and cytosolic extracts revealed that only nuclear p/CIP complexes possess histone acetyltransferase activity. Collectively, these results suggest that cellular compartmentalization of NCoA/SRC proteins could potentially regulate nuclear hormone receptor-mediated events as well as integrating signals in response to different environmental cues.