The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

OBJECTIVE: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. METHODS: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. RESULTS: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. CONCLUSIONS: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

The Impact of Providing Material Benefits to Improve Access to Food on Clinical Parameters, Dietary Intake, and Household Food Insecurity in People with Diabetes: A Systematic Review with Narrative Synthesis.

The high cost of healthy foods makes maintaining a healthy dietary pattern challenging, particularly among people with diabetes who are experiencing food insecurity. The objectives of this study were to: 1) review evidence on the impact of providing material benefits (e.g., food coupons/vouchers, free food, or financial subsidies/incentives) to improve access to food on clinical parameters, dietary intake, and household food insecurity in people with diabetes, and 2) review relevant economic evidence. Six databases were searched from inception to March 2023 for longitudinal studies with quantitative outcomes. Twenty-one studies were included in the primary review and 2 in the economic analysis. Risk of bias was high in 20 studies and moderate in 1 study. The number of randomized controlled trials and nonrandomized studies reporting statistically significant improvement, alongside Grading of Recommendations Assessment, Development, and Evaluation (GRADE) certainty of the evidence was: HbA1c: 1/6 and 4/12 (very low), systolic blood pressure: 0/3 and 1/8 (very low), diastolic blood pressure: 0/3 and 1/7 (very low), BMI: 0/5 and 2/8 (very low), body weight: 0/0 and 1/3 (very low), hypoglycemia: 1/2 and 1/2 (very low), daily intake of fruits and vegetables: 1/1 and 1/3 (very low), daily intake of whole grains: 0/0 and 0/2 (very low), overall diet quality: 2/2 and 1/1 (low), and household food insecurity: 2/3 and 0/0 (very low). The 2 studies included in the economic analysis showed no difference in Medicare spending from Supplemental Nutrition Assistance Program participation and cost-savings from medically tailored meals in an economic simulation. Overall, providing material benefits to improve access to food for people with diabetes may improve household food insecurity, fruit and vegetable intake, and overall diet quality, but effects on clinical parameters and whole grain intake are unclear. The certainty of evidence was very low to low by GRADE. PROSPERO (CRD42021212951).

Healthy food prescription incentive programme for adults with type 2 diabetes who are experiencing food insecurity: protocol for a randomised controlled trial, modelling and implementation studies.

INTRODUCTION: The high cost of many healthy foods poses a challenge to maintaining optimal blood glucose levels for adults with type 2 diabetes mellitus who are experiencing food insecurity, leading to diabetes complications and excess acute care usage and costs. Healthy food prescription programmes may reduce food insecurity and support patients to improve their diet quality, prevent diabetes complications and avoid acute care use. We will use a type 2 hybrid-effectiveness design to examine the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) of a healthy food prescription incentive programme for adults experiencing food insecurity and persistent hyperglycaemia. A randomised controlled trial (RCT) will investigate programme effectiveness via impact on glycosylated haemoglobin (primary outcome), food insecurity, diet quality and other clinical and patient-reported outcomes. A modelling study will estimate longer-term programme effectiveness in reducing diabetes-related complications, resource use and costs. An implementation study will examine all RE-AIM domains to understand determinants of effective implementation and reasons behind programme successes and failures. METHODS AND ANALYSIS: 594 adults who are experiencing food insecurity and persistent hyperglycaemia will be randomised to a healthy food prescription incentive (n=297) or a healthy food prescription comparison group (n=297). Both groups will receive a healthy food prescription. The incentive group will additionally receive a weekly incentive (CDN$10.50/household member) to purchase healthy foods in supermarkets for 6 months. Outcomes will be assessed at baseline and follow-up (6 months) in the RCT and analysed using mixed-effects regression. Longer-term outcomes will be modelled using the UK Prospective Diabetes Study outcomes simulation model-2. Implementation processes and outcomes will be continuously measured via quantitative and qualitative data. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Calgary and the University of Alberta. Findings will be disseminated through reports, lay summaries, policy briefs, academic publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04725630. PROTOCOL VERSION: Version 1.1; February 2022.

Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation.

Hematopoietic disorders, particularly hemolytic anemias, commonly lead to bone loss. We have previously reported that actively proliferating cancer cells stimulate osteoclastogenesis from late precursors in a RANKL-independent manner. We theorized that cancer cells exploit the physiological role of bone resorption to support expanding hematopoietic bone marrow and examined if hematopoietic cells can trigger osteoclastogenesis. Using phlebotomy-induced acute anemia in mice, we found strong correlation between augmented erythropoiesis and increased osteoclastogenesis. Conditioned medium (CM) from K562 erythroleukemia cells and primary mouse erythroblasts stimulated osteoclastogenesis when added to RANKL-primed precursors from mouse bone marrow or RAW264.7 cells. Using immunoblotting and mass spectrometry, PRDX2 was identified as a factor produced by erythroid cells in vitro and in vivo. PRDX2 was detected in K562-derived exosomes, and inhibiting exosomal release significantly decreased the osteoclastogenic capacity of K562 CM. Recombinant PRDX2 induced osteoclast formation from RANKL-primed primary or RAW 264.7 precursors to levels comparable to achieved with continuous RANKL treatment. Thus, increased bone marrow erythropoiesis secondary to anemia leads to upregulation of PRDX2, which is released in the exosomes and acts to induce osteoclast formation. Increased bone resorption by the osteoclasts expands bone marrow cavity, which likely plays a supporting role to increase blood cell production.

Cups for COVID: rapid implementation of a harm reduction initiative to support populations experiencing homelessness during the COVID-19 pandemic.

SETTING: As of June 10, 2020, 37 people experiencing homelessness or unstable housing in Calgary, Alberta, had developed lab-confirmed COVID-19. Spread occurred despite standard outbreak controls at affected shelter and supportive housing sites. Among these 37 cases, drink sharing was frequently identified as a modifiable mode of possible transmission. We collaborated with emergency shelters, a supportive housing site, and street and encampment outreach groups, using mixed service delivery by health staff, non-profits, and peers with lived experience with homelessness. INTERVENTION: To empower individuals to decrease COVID-19 transmission using a harm reduction approach, we provided disposable paper cups to service providers for distribution to clients. Service providers tracked the number of cups distributed. To assess effectiveness, we interviewed staff and peers who distributed the cups. OUTCOMES: Cup distribution was highest among populations with higher rates of alcohol use, and the intervention was well received by people who drink alcohol regularly, providing unique opportunities to promote COVID-19 awareness and safer drinking practices. Providers to these populations reported enthusiastic client engagement and repeat requests for cups for safer drinking. Intervention usefulness was limited in contexts with low alcohol consumption and in the absence of paired COVID-19 education. Provider reports suggest appropriate disposal of these cups after use. IMPLICATIONS: Disposable cups are a novel, rapidly implementable, low-cost harm reduction tool to empower people experiencing homelessness to reduce the risk of COVID-19 transmission due to drink sharing, ideally as part of a larger harm reduction and community education strategy.

RéSUMé: LIEU: Au 10 juin 2020, trente-sept (37) personnes sans abri ou vivant en logement instable à Calgary (Alberta) avaient contracté une infection par la COVID-19 confirmée en laboratoire. La maladie s'est propagée malgré les mesures types de contrôle des éclosions dans les refuges et les logements supervisés touchés. Parmi ces 37 cas, le partage de boissons a souvent été défini comme un mode de transmission modifiable possible. En collaboration avec des refuges d'urgence, un complexe de logements supervisés et des groupes menant des activités de proximité dans la rue et les campements, nous avons assuré une prestation de services mixte par des personnels de santé, des organisations sans but lucratif et des pairs ayant une expérience vécue de sans-abrisme. INTERVENTION: Pour donner à chaque personne les moyens de réduire la transmission de la COVID-19 selon une approche de réduction des méfaits, nous avons fourni aux dispensateurs de services des gobelets en papier jetables à distribuer à leurs usagers. Les dispensateurs ont fait un suivi du nombre de gobelets distribués. Pour évaluer l'efficacité de l'initiative, nous avons interviewé le personnel et les pairs ayant distribué les gobelets. RéSULTATS: Le nombre de gobelets distribués a été le plus élevé dans les populations ayant des taux élevés de consommation d'alcool, et l'intervention a été bien accueillie par les personnes qui consomment régulièrement de l'alcool; elle a offert des occasions uniques de faire de la sensibilisation à la COVID-19 et de promouvoir une pratique de consommation de boissons à moindre risque. Les intervenants auprès de ces populations ont fait état d'une participation enthousiaste des usagers et de demandes répétées de gobelets pour boire sans s'exposer au risque de contracter la maladie. L'utilité de l'intervention a été limitée dans les contextes de faible consommation d'alcool et en l'absence d'une sensibilisation conjointe à la COVID-19. Selon les rapports des dispensateurs de services, les gobelets ont été correctement éliminés après usage. CONSéQUENCES: Les gobelets jetables sont un nouvel outil de réduction des méfaits à prix abordable qui peut être mis en œuvre rapidement pour donner aux personnes aux prises avec le sans-abrisme les moyens de réduire le risque de transmission de la COVID-19 lorsqu'elles partagent des boissons, idéalement dans le cadre d'une stratégie de réduction des méfaits et de sensibilisation de proximité.

Development of a technique for MRI gold-standard direct volumetric measurement of complex joint effusion, and validation at the hip.

OBJECTIVE: Accurate joint fluid quantification on MRI cannot simply rely on measuring the maximum fluid depth or using an ellipsoid approximation as this does not fully characterize the complex shape of a fluid-filled joint. As per the Outcome Measurement in Rheumatology (OMERACT) filter, we sought to evaluate the feasibility, reliability, and validity of a semi-automated supervised technique to quantify hip effusion volume. MATERIALS AND METHODS: Ninety-three hip osteoarthritis patients were imaged with coronal short TI inversion recovery (STIR) and sagittal intermediate weighted fat-suppressed (IWFS) sequences at two time points (Fig. 1). Volumetric quantitative measurement (VQM) of joint fluid and measurement of the largest femoral neck fluid thickness (FTM) was performed using the custom MATLAB software. Self-reported Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and clinical measures of pain, stiffness, and function were recorded. RESULTS: Inter-observer reliability was significantly higher for VQM than FTM (ICC = 0.96 vs. 0.85, p < 0.05). VQM and FTM correlated moderately (r = 0.76, p < 0.0001). There was significantly more articular fluid in symptomatic than asymptomatic hips at baseline (mean = 9.8 vs. 5.9 mL). Volumetric quantitative measurement generally displayed more frequent and stronger correlations to clinical parameters than FTM. Volumetric quantitative measurement required 3.9 min/hip vs. < 1 min/hip for femoral neck fluid thickness. CONCLUSION: Volumetric quantitative measurement of joint effusion can serve as an MRI gold-standard, could apply to other joints and collections, and is highly suited to future automation.

Low back pain and radiographic severity as predictors in hip osteoarthritis patients receiving steroid injection therapy.

INTRODUCTION: We investigated the effects of lower back pain (LBP) on measures of pain, disability, and function in highly symptomatic hip OA patients receiving intra-articular steroid injection (IASI) therapy. We also investigated the effect of radiographic severity of hip OA for comparison to LBP. METHODS: 97 consenting subjects with symptomatic hip OA presenting for IASI were evaluated at baseline, assessed over an 8-week period, and followed at least 1 year later for new arthroplasty. At baseline and 8 weeks follow-up patient demographics, presence/absence of back pain, physical function tests, a single anteroposterior pelvis x-ray, and subjective scores of pain, stiffness and function (VAS and WOMAC) were collected. We also followed which subjects proceeded to obtain total hip arthroplasty in the examined hip. RESULTS: Cohorts with LBP reported significantly worse scores for all of VAS pain and WOMAC questionnaires but showed no difference in ROM and were not more likely to proceed to arthroplasty. Cohorts with severe radiographic OA had significantly worsened scores for stiffness (χ2 = 6.74, p = 0.009), decreased ROM (p < 0.01), and were more likely to proceed to arthroplasty (χ2 = 9.79, p = 0.044). DISCUSSION: Back pain has a substantial effect on clinical parameters relevant to assessment of severity of hip OA, especially self-reported pain and function. This finding highlights LBP as a significant confounding factor in hip OA patient assessments and will inform future studies to determine the most effective treatment strategies for hip OA patients.

From priority to endgame: the Region of Peel Living Tobacco-Free strategy.

Tobacco use presents a tremendous burden on population health and remains the leading preventable cause of morbidity and mortality worldwide. Building on tobacco control successes to date, public health agencies are increasingly aligning with the international "Tobacco Endgame" initiative targeting decreases in tobacco use to less than 5% by the year 2025. The local implementation of this initiative follows a decade of work at Region of Peel-Public Health (RoP-PH), a local health department in Ontario, Canada, which made "Living Tobacco-Free" (LTF) a strategic priority in 2009 with a tactical framework encompassing Research, Protection, Prevention, and Cessation. This commentary provides an overview of the results observed by this local health department's decision to make LTF a strategic priority and discusses the department's next steps in developing a Theory of Change to systematically align continuing efforts to the call for a "Tobacco Endgame".

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

OBJECTIVE: To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA). METHODS: HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts. RESULTS: HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56). CONCLUSION: HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

Bone Health in Patients With Hematopoietic Disorders of Bone Marrow Origin: Systematic Review and Meta- Analysis.

Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.

Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations.

KEY POINTS: Most missense long QT syndrome type 2 (LQTS2) mutations result in Kv11.1 channels that show reduced levels of membrane expression. Pharmacological chaperones that rescue mutant channel expression could have therapeutic potential to reduce the risk of LQTS2-associated arrhythmias and sudden cardiac death, but only if the mutant Kv11.1 channels function normally (i.e. like WT channels) after membrane expression is restored. Fewer than half of mutant channels exhibit relatively normal function after rescue by low temperature. The remaining rescued missense mutant Kv11.1 channels have perturbed gating and/or ion selectivity characteristics. Co-expression of WT subunits with gating defective missense mutations ameliorates but does not eliminate the functional abnormalities observed for most mutant channels. For patients with mutations that affect gating in addition to expression, it may be necessary to use a combination therapy to restore both normal function and normal expression of the channel protein. ABSTRACT: In the heart, Kv11.1 channels pass the rapid delayed rectifier current (IKr ) which plays critical roles in repolarization of the cardiac action potential and in the suppression of arrhythmias caused by premature stimuli. Over 500 inherited mutations in Kv11.1 are known to cause long QT syndrome type 2 (LQTS2), a cardiac electrical disorder associated with an increased risk of life threatening arrhythmias. Most missense mutations in Kv11.1 reduce the amount of channel protein expressed at the membrane and, as a consequence, there has been considerable interest in developing pharmacological agents to rescue the expression of these channels. However, pharmacological chaperones will only have clinical utility if the mutant Kv11.1 channels function normally after membrane expression is restored. The aim of this study was to characterize the gating phenotype for a subset of LQTS2 mutations to assess what proportion of mutations may be suitable for rescue. As an initial screen we used reduced temperature to rescue expression defects of mutant channels expressed in Xenopus laevis oocytes. Over half (∼56%) of Kv11.1 mutants exhibited functional gating defects that either dramatically reduced the amount of current contributing to cardiac action potential repolarization and/or reduced the amount of protective current elicited in response to premature depolarizations. Our data demonstrate that if pharmacological rescue of protein expression defects is going to have clinical utility in the treatment of LQTS2 then it will be important to assess the gating phenotype of LQTS2 mutations before attempting rescue.