A novel role of RNase L in the development of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and affects about 25% of the population globally. NAFLD has the potential to cause significant liver damage in many patients because it can progress to nonalcoholic steatohepatitis (NASH) and cirrhosis, which substantially increases disease morbidity and mortality. Despite the key role of innate immunity in the disease progression, the underlying molecular and pathogenic mechanisms remain to be elucidated. RNase L is a key enzyme in interferon action against viral infection and displays pleiotropic biological functions such as control of cell proliferation, apoptosis, and autophagy. Recent studies have demonstrated that RNase L is involved in innate immunity. In this study, we revealed that RNase L contributed to the development of NAFLD, which further progressed to NASH in a time-dependent fashion after RNase L wild-type (WT) and knockout mice were fed with a high-fat and high-cholesterol diet. RNase L WT mice showed significantly more severe NASH, evidenced by widespread macro-vesicular steatosis, hepatocyte ballooning degeneration, inflammation, and fibrosis, although physiological and biochemical data indicated that both types of mice developed obesity, hyperglycemia, hypercholesterolemia, dysfunction of the liver, and systemic inflammation at different extents. Further investigation demonstrated that RNase L was responsible for the expression of some key genes in lipid metabolism, inflammation, and fibrosis signaling. Taken together, our results suggest that a novel therapeutic intervention for NAFLD may be developed based on regulating the expression and activity of RNase L.

Cervical Screening Practices and Outcomes for Young Women in Response to Changed Guidelines in Calgary, Canada, 2007-2016.

OBJECTIVE: The aim of the study was to describe temporal trends in screening and outcomes for women, after changes in guidelines in Alberta, Canada, that raised starting age to 21 years, then to 25 years of age, and reduced frequency to 3 yearly. MATERIALS AND METHODS: Calgary Laboratory Information System data were used to examine screening rates, follow-up procedures, and cancer among women 10-29 years from 2007 to 2016 in the whole population of Calgary. Interrupted time-series analyses were used to assess changes in screening and subsequent diagnostic procedures over the 10-year period. RESULTS: Annual screening rates dropped by approximately 10% at all ages older than 15 years after the 2009 Alberta cervical cancer screening guidelines, followed by a steady decrease. Further change continued subsequent to minimal apparent effect of the 2013 Canadian Task Force on Preventive Health Care guidelines. The rates of abnormal test results decreased in concert with decreased screening. No increases in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2/3, or invasive cervical cancer rates were observed after reduced testing. CONCLUSIONS: The largest decrease in screening and follow-up procedures occurred in the period immediately after implementation of 2009 Alberta screening guidelines. The number of consequent procedures also decreased in proportion to decreased screening, but there was no increase in cancer rates. Starting screening at the age of 25 years and reducing intervals seem to be safe.

Validation of a case definition for depression in administrative data against primary chart data as a reference standard.

BACKGROUND: Because the collection of mental health information through interviews is expensive and time consuming, interest in using population-based administrative health data to conduct research on depression has increased. However, there is concern that misclassification of disease diagnosis in the underlying data might bias the results. Our objective was to determine the validity of International Classification of Disease (ICD)-9 and ICD-10 administrative health data case definitions for depression using review of family physician (FP) charts as the reference standard. METHODS: Trained chart reviewers reviewed 3362 randomly selected charts from years 2001 and 2004 at 64 FP clinics in Alberta (AB) and British Columbia (BC), Canada. Depression was defined as presence of either: 1) documentation of major depressive episode, or 2) documentation of specific antidepressant medication prescription plus recorded depressed mood. The charts were linked to administrative data (hospital discharge abstracts and physician claims data) using personal health numbers. Validity indices were estimated for six administrative data definitions of depression using three years of administrative data. RESULTS: Depression prevalence by chart review was 15.9-19.2% depending on year, region, and province. An ICD administrative data definition of '2 depression claims with depression ICD codes within a one-year window OR 1 discharge abstract data (DAD) depression diagnosis' had the highest overall validity, with estimates being 61.4% for sensitivity, 94.3% for specificity, 69.7% for positive predictive value, and 92.0% for negative predictive value. Stratification of the validity parameters for this case definition showed that sensitivity was fairly consistent across groups, however the positive predictive value was significantly higher in 2004 data compared to 2001 data (78.8 and 59.6%, respectively), and in AB data compared to BC data (79.8 and 61.7%, respectively). CONCLUSIONS: Sensitivity of the case definition is often moderate, and specificity is often high, possibly due to undercoding of depression. Limitations to this study include the use of FP charts data as the reference standard, given the potential for missed or incorrect depression diagnoses. These results suggest that that administrative data can be used as a source of information for both research and surveillance purposes, while remaining aware of these limitations.

MicroRNA-98 regulates hepatic cholesterol metabolism via targeting sterol regulatory element-binding protein 2.

Hypercholesterolemia is an important risk factor for coronary heart disease. Although a lot of research has been conducted, the regulation of cholesterol metabolism is still largely unknown. Some miRNAs have been found to play critical role in the cholesterol metabolism. MiR-98 is a miRNA whose function has been reported mainly in tumorigenesis. In this study, we elucidate a novel role of miR-98 in cholesterol metabolism. We found that the expression of miR-98 was decreased significantly in hypercholesterolemic patients compared with healthy control subjects. Furthermore, we identified that SREBP-2, an important transcriptional factor in cholesterol metabolism, was a direct target of miR-98. Overexpression of miR-98 significantly repressed the 3'-UTR reporter activities of SREBP-2 in a dose-dependent manner in HepG2 cells, while the effect of miR-98 was blocked when the binding site of miR-98 within the SREBP-2 3'-UTR was mutated. And overexpression of miR-98 reduced both the mRNA and protein levels of HMGCR and LDLR significantly in vitro, which are two target genes of SREBP-2. Furthermore, MiR-98 overexpression reduced the intracellular total cholesterol levels dramatically. Moreover, we overexpressed the miR-98 by lentiviral tail vein injection in vivo. Compared with the control mice, the miR-98 overexpression mice showed lower serum cholesterol level and decreased SREBP-2, HMGCR as well as LDLR expression. Our data confirmed that reduced expression of miR-98 potentially contributes to disturbance of cholesterol metabolism. MiR-98 might be a novel therapeutic target to hypercholesterolemia.

Association between afterhours admission to the intensive care unit, strained capacity, and mortality: a retrospective cohort study.

BACKGROUND: Admission to the intensive care unit (ICU) outside daytime hours has been shown to be variably associated with increased morbidity and mortality. We aimed to describe the characteristics and outcomes of patients admitted to the ICU afterhours (22:00-06:59 h) in a large Canadian health region. We further hypothesized that the association between afterhours admission and mortality would be modified by indicators of strained ICU capacity. METHODS: This is a population-based cohort study of 12,265 adults admitted to nine ICUs in Alberta from June 2012 to December 2014. We used a path-analysis modeling strategy and mixed-effects multivariate regression analysis to evaluate direct and integrated associations (mediated through Acute Physiology and Chronic Health Evaluation (APACHE) II score) between afterhours admission (22:00-06:59 h) and ICU mortality. Further analysis examined the effects of strained ICU capacity and varied definitions of afterhours and weekend admissions. ICU occupancy ≥ 90% or clustering of admissions (≥ 0.15, defined as number of admissions 2 h before or after the index admission, divided by the number of ICU beds) were used as indicators of strained capacity. RESULTS: Of 12,265 admissions, 34.7% (n = 4251) occurred afterhours. The proportion of afterhours admissions varied amongst ICUs (range 26.7-37.8%). Patients admitted afterhours were younger (median (IQR) 58 (44-70) vs 60 (47-70) years, p < 0.0001), more likely to have a medical diagnosis (75.9% vs 72.1%, p < 0.0001), and had higher APACHE II scores (20.9 (8.6) vs 19.9 (8.3), p < 0.0001). Crude ICU mortality was greater for those admitted afterhours (15.9% vs 14.1%, p = 0.007), but following multivariate adjustment there was no direct or integrated effect on ICU mortality (odds ratio (OR) 1.024; 95% confidence interval (CI) 0.923-1.135, p = 0.658). Furthermore, direct and integrated analysis showed no association of afterhours admission and hospital mortality (p = 0.90) or hospital length of stay (LOS) (p = 0.27), although ICU LOS was shorter (p = 0.049). Early-morning admission (00:00-06:59 h) with ICU occupancy ≥ 90% was associated with short-term (≤ 7 days) and all-cause ICU mortality. CONCLUSIONS: One-third of critically ill patients are admitted to the ICU afterhours. Afterhours ICU admission was not associated with greater mortality risk in most circumstances but was sensitive to strained ICU capacity.

Impact of clinical presentation and presence of coronary sclerosis on long-term outcome of patients with non-obstructive coronary artery disease.

BACKGROUND: Non-obstructive coronary artery disease (NOCAD) is a common finding on coronary angiography. Our goal was to evaluate the long-term prognosis of NOCAD patients with stable angina (SA). METHODS: The study cohort consisted of 7478 NOCAD patients with normal EF (≥ 50%), and SA who underwent coronary angiography between 1995 and 2012. We compared NOCAD patients (stenosis< 50%) with 10,906 patients with stable obstructive CAD (≥ 50%). The primary endpoint was all-cause mortality. Secondary endpoints included repeat angiography, progressive CAD, and PCI. A second comparison group consisted of 7344 patients with NOCAD presenting with an ACS. Rates of all-cause mortality of NOCAD ACS patients were compared to NOCAD SA patients. RESULTS: Median follow-up time was 6.5 years. NOCAD patients had a lower risk of all-cause mortality compared to CAD patients (HR CAD vs. NOCAD 1.33 (1.19-1.49); p < 0.001). This was driven by patients with normal coronary arteries (HR CAD vs. normal 1.63 (1.36-1.94), p < 0.001), whereas patients with minimal disease (> 0% and < 50%) were at similar risk as CAD patients (HR CAD vs. minimal 1.08 (0.99-1.29), p = 0.06). In NOCAD patients, the strongest predictors of all-cause mortality were age and minimal disease. SA patients with NOCAD had low rates of repeat angiography (7.3%), future CAD (2.3%) and PCI (1.7%). NOCAD ACS patients had a 41% increase in all-cause mortality risk compared to NOCAD SA patients (HR 1.41 (1.25-1.6), p < 0.001). CONCLUSIONS: This study underlines the importance of minimal CAD, as it is not a benign disease entity and portends a similar risk as stable obstructive CAD.

Validation of a Case Definition for Pediatric Brain Injury Using Administrative Data.

BACKGROUND: Health administrative data are a common population-based data source for traumatic brain injury (TBI) surveillance and research; however, before using these data for surveillance, it is important to develop a validated case definition. The objective of this study was to identify the optimal International Classification of Disease , edition 10 (ICD-10), case definition to ascertain children with TBI in emergency room (ER) or hospital administrative data. We tested multiple case definitions. METHODS: Children who visited the ER were identified from the Regional Emergency Department Information System at Alberta Children's Hospital. Secondary data were collected for children with trauma, musculoskeletal, or central nervous system complaints who visited the ER between October 5, 2005, and June 6, 2007. TBI status was determined based on chart review. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each case definition. RESULTS: Of 6639 patients, 1343 had a TBI. The best case definition was, "1 hospital or 1 ER encounter coded with an ICD-10 code for TBI in 1 year" (sensitivity 69.8% [95% confidence interval (CI), 67.3-72.2], specificity 96.7% [95% CI, 96.2-97.2], PPV 84.2% [95% CI 82.0-86.3], NPV 92.7% [95% CI, 92.0-93.3]). The nonspecific code S09.9 identified >80% of TBI cases in our study. CONCLUSIONS: The optimal ICD-10-based case definition for pediatric TBI in this study is valid and should be considered for future pediatric TBI surveillance studies. However, external validation is recommended before use in other jurisdictions, particularly because it is plausible that a larger proportion of patients in our cohort had milder injuries.

Blood pressure at age 60-65 versus age 70-75 and vascular dementia: a population based observational study.

BACKGROUND: Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. METHODS: This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. RESULTS: After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. CONCLUSION: High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

ACSC Indicator: testing reliability for hypertension.

BACKGROUND: With high-quality community-based primary care, hospitalizations for ambulatory care sensitive conditions (ACSC) are considered avoidable. The purpose of this study was to test the inter-physician reliability of judgments of avoidable hospitalizations for one ACSC, uncomplicated hypertension, derived from medical chart review. METHODS: We applied the Canadian Institute for Health Information's case definition to obtain a random sample of patients who had an ACSC hospitalization for uncomplicated hypertension in Calgary, Alberta. Medical chart review was conducted by three experienced internal medicine specialists. Implicit methods were used to judge avoidability of hospitalization using a validated 5-point scale. RESULTS: There was poor agreement among three physicians raters when judging the avoidability of 82 ACSC hospitalizations for uncomplicated hypertension (κ = 0.092). The κ also remained low when assessing agreement between raters 1 and 3 (κ = 0.092), but the κ was lower (less than chance agreement) for raters 1 and 2 (κ = -0.119) and raters 2 and 3 (κ = -0.008). When the 5-point scale was dichotomized, there was fair agreement among three raters (κ = 0.217). The proportion of ACSC hospitalizations for uncomplicated hypertension that were rated as avoidable was 32.9%, 6.1% and 26.8% for raters 1, 2, and 3, respectively. CONCLUSIONS: This study found a low proportion of ACSC hospitalization were rated as avoidable, with poor to fair agreement of judgment between physician raters. This suggests that the validity and utility of this health indicator is questionable. It points to a need to abandon the use of ACSC entirely; or alternatively to work on the development of explicit criteria for judging avoidability of hospitalization for ACSC such as hypertension.

Methods of defining hypertension in electronic medical records: validation against national survey data.

BACKGROUND: Electronic medical records (EMR) can be a cost-effective source for hypertension surveillance. However, diagnosis of hypertension in EMR is commonly under-coded and warrants the needs to review blood pressure and antihypertensive drugs for hypertension case identification. METHODS: We included all the patients actively registered in The Health Improvement Network (THIN) database, UK, on 31 December 2011. Three case definitions using diagnosis code, antihypertensive drug prescriptions and abnormal blood pressure, respectively, were used to identify hypertension patients. We compared the prevalence and treatment rate of hypertension in THIN with results from Health Survey for England (HSE) in 2011. RESULTS: Compared with prevalence reported by HSE (29.7%), the use of diagnosis code alone (14.0%) underestimated hypertension prevalence. The use of any of the definitions (38.4%) or combination of antihypertensive drug prescriptions and abnormal blood pressure (38.4%) had higher prevalence than HSE. The use of diagnosis code or two abnormal blood pressure records with a 2-year period (31.1%) had similar prevalence and treatment rate of hypertension with HSE. CONCLUSIONS: Different definitions should be used for different study purposes. The definition of 'diagnosis code or two abnormal blood pressure records with a 2-year period' could be used for hypertension surveillance in THIN.

Effects of longitudinal changes in Charlson comorbidity on prognostic survival model performance among newly diagnosed patients with hypertension.

BACKGROUND: To assess the use of updated comorbidity information over time on ability to predict mortality among adults with newly diagnosed hypertension. METHODS: We studied adults 18 years and older with an incident diagnosis of hypertension from Alberta, Canada. We compared the prognostic performance of Cox regression models using Charlson comorbidities as time-invariant covariates at baseline (TIC) versus models including Charlson comorbidities as time-varying covariates (TVC) using Akaike Information Criterion (AIC) for testing goodness of fit. RESULTS: The strength of the association between important prognostic clinical variables and mortality varied by modeling technique; for example, myocardial infarction was less strongly associated with mortality in the TIC model (Hazard Ratio 1.07; 95% Confidence Interval (CI): 1.05 to 1.1) than in the TVC model (HR 1.20; 95% CI: 1.18 to 1.22). All TVC models slightly outperformed TIC models, regardless of the method used to adjust for comorbid conditions (individual Charlson Comorbidities, count of comorbidities or indices). The TVC model including all 17 Charlson comorbidities as individual independent variables showed the best fit and performance. CONCLUSION: Accounting for changes in patient comorbidity status over time more accurately captures a patient's health risk and slightly improves predictive model fit and performance than traditional methods using TIC assessment.

Coding of obesity in administrative hospital discharge abstract data: accuracy and impact for future research studies.

BACKGROUND: Obesity is a pervasive problem and a popular subject of academic assessment. The ability to take advantage of existing data, such as administrative databases, to study obesity is appealing. The objective of our study was to assess the validity of obesity coding in an administrative database and compare the association between obesity and outcomes in an administrative database versus registry. METHODS: This study was conducted using a coronary catheterization registry and an administrative database (Discharge Abstract Database (DAD)). A Body Mass Index (BMI) ≥30 kg/m2 within the registry defined obesity. In the DAD obesity was defined by diagnosis codes E65-E68 (ICD-10). The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of an obesity diagnosis in the DAD was determined using obesity diagnosis in the registry as the referent. The association between obesity and outcomes was assessed. RESULTS: The study population of 17380 subjects was largely male (68.8%) with a mean BMI of 27.0 kg/m2. Obesity prevalence was lower in the DAD than registry (2.4% vs. 20.3%). A diagnosis of obesity in the DAD had a sensitivity 7.75%, specificity 98.98%, NPV 80.84% and PPV 65.94%. Obesity was associated with decreased risk of death or re-hospitalization, though non-significantly within the DAD. Obesity was significantly associated with an increased risk of cardiac procedure in both databases. CONCLUSIONS: Overall, obesity was poorly coded in the DAD. However, when coded, it was coded accurately. Administrative databases are not an optimal datasource for obesity prevalence and incidence surveillance but could be used to define obese cohorts for follow-up.

Effectiveness of a Self-Monitoring App in Supporting Physical Activity Maintenance Among Rural Canadians With Cancer After an Exercise Oncology Program: Cluster Randomized Controlled Trial.

BACKGROUND: Despite the benefits of physical activity (PA) for individuals with cancer, most remain insufficiently active. Exercise oncology interventions can improve PA levels. Individuals struggle to maintain PA levels after interventions because of persistent psychological and environmental PA barriers. Health technology (eHealth) may address some PA barriers and deliver effective, scalable PA interventions in oncology, yet its effectiveness for changing PA levels remains mixed. Using eHealth to support PA maintenance among rural populations with cancer, who may need greater PA support given lower PA levels and worse health outcomes, remains under-studied. OBJECTIVE: This study examined the effectiveness of an app-based self-monitoring intervention in supporting PA maintenance among rural populations with cancer after a supervised web-based exercise oncology program. METHODS: This 2-arm, cluster randomized controlled trial was embedded within the Exercise for Cancer to Enhance Living Well (EXCEL) effectiveness-implementation study. Upon consent, participants were randomized 1:1 by EXCEL class clusters to the intervention (24 weeks of app-based PA self-monitoring) or waitlist control (app access after 24 weeks). Both groups completed a 12-week supervised web-based exercise oncology program followed by a 12-week self-directed PA maintenance period. Baseline demographics, eHealth literacy, and patient-reported outcomes were compared using chi-square and 2-tailed t tests. App use was measured throughout the intervention. The primary outcome-self-reported moderate-to-vigorous PA (MVPA) minutes-and secondary outcomes-objective MVPA minutes and steps and app usability ratings-were collected at baseline, 12 weeks, and 24 weeks. Intervention effects on self-report MVPA maintenance were assessed via linear mixed modeling, with secondary outcomes explored descriptively. RESULTS: Of the 359 eligible EXCEL participants, 205 (57.1%) consented, 199 (55.4%; intervention: 106/199, 53.3%; control: 93/199, 46.7%) started the study, and 183 (51%; intervention: 100/183, 54.6%; control: 83/183, 45.4%) and 141 (39.3%; intervention: 69/141, 48.9%; control: 72/141, 51.1%) completed 12- and 24-week measures, respectively. Mean age was 57.3 (SD 11.5) years. Most participants were female (174/199, 87.4%), White (163/199, 81.9%), and diagnosed with breast cancer (108/199, 54.3%). Median baseline self-report weekly MVPA minutes were 60.0 (IQR 0-180) and 40.0 (IQR 0-135) for the intervention and waitlist control groups, respectively (P=.74). Median app use duration was 10.3 (IQR 1.3-23.9) weeks, with 9.6 (IQR 4.4-17.8) self-monitoring entries/week. Both groups increased their weekly MVPA minutes significantly at 12 weeks (P<.001) and maintained the increases at 24 weeks (P<.001), relative to baseline, with no between-group differences (P=.87). The intervention group had significantly higher step counts for 7 of the 12 weeks during the PA maintenance period (P=.048 to <.001). CONCLUSIONS: The app-based self-monitoring intervention did not improve MVPA maintenance but may have contributed to increased step counts during the PA maintenance period. More work is needed to realize the full potential of eHealth in exercise oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04790578; https://clinicaltrials.gov/study/NCT04790578. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2021.106474.

Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review.

CONTEXT: Symptomatic venous thromboembolism (VTE) after total or partial knee arthroplasty (TPKA) and after total or partial hip arthroplasty (TPHA) are proposed patient safety indicators, but its incidence prior to discharge is not defined. OBJECTIVE: To establish a literature-based estimate of symptomatic VTE event rates prior to hospital discharge in patients undergoing TPHA or TPKA. DATA SOURCES: Search of MEDLINE, EMBASE, and the Cochrane Library (1996 to 2011), supplemented by relevant articles. STUDY SELECTION: Reports of incidence of symptomatic postoperative pulmonary embolism or deep vein thrombosis (DVT) before hospital discharge in patients who received VTE prophylaxis with either a low-molecular-weight heparin or a subcutaneous factor Xa inhibitor or oral direct inhibitor of factors Xa or IIa. DATA EXTRACTION AND SYNTHESIS: Meta-analysis of randomized clinical trials and observational studies that reported rates of postoperative symptomatic VTE in patients who received recommended VTE prophylaxis after undergoing TPHA or TPKA. Data were independently extracted by 2 analysts, and pooled incidence rates of VTE, DVT, and pulmonary embolism were estimated using random-effects models. RESULTS: The analysis included 44,844 cases provided by 47 studies. The pooled rates of symptomatic postoperative VTE before hospital discharge were 1.09% (95% CI, 0.85%-1.33%) for patients undergoing TPKA and 0.53% (95% CI, 0.35%-0.70%) for those undergoing TPHA. The pooled rates of symptomatic DVT were 0.63% (95% CI, 0.47%-0.78%) for knee arthroplasty and 0.26% (95% CI, 0.14%-0.37%) for hip arthroplasty. The pooled rates for pulmonary embolism were 0.27% (95% CI, 0.16%-0.38%) for knee arthroplasty and 0.14% (95% CI, 0.07%-0.21%) for hip arthroplasty. There was significant heterogeneity for the pooled incidence rates of symptomatic postoperative VTE in TPKA studies but less heterogeneity for DVT and pulmonary embolism in TPKA studies and for VTE, DVT, and pulmonary embolism in TPHA studies. CONCLUSION: Using current VTE prophylaxis, approximately 1 in 100 patients undergoing TPKA and approximately 1 in 200 patients undergoing TPHA develops symptomatic VTE prior to hospital discharge.

Care gaps in achieving cholesterol targets in people with diabetes: A population-based study in a universal health care setting.

AIMS: Statins are first line therapy in people with diabetes. Little is known about real-world statin intensity use and low-density lipoprotein cholesterol (LDL-C) levels achieved. We aimed to describe statin intensity used, achievement of LDL-C targets, and factors associated with achieving targets among adults with diabetes. METHODS: This population based (∼4.3 million), retrospective observational study, used clinical and administrative databases. Statin use by intensity, adherence, and achievement of LDL-C targets in adults with diabetes were described. Multiple logistic regression assessed the factors associated with achieving targets. RESULTS: Out of 331,312 individuals with diabetes, 88% had an index LDL-C test. At follow up, 31% overall did not achieve LDL-C targets and overall adherence was 66%. Failure to achieve targets was 49%, 30%, and 25% in low-, moderate-, and high-intensity statin groups, respectively. Those who were older, males, had a history of myocardial infarction, stroke, congestive heart failure, renal disease, better adherence, and higher intensity statin users were more likely to achieve targets. CONCLUSIONS: One-third of people on statins did not achieve targets. Strategies to fill the gap between ideal and current levels of LDL-C achieved are needed if the benefits of statins demonstrated in trials are to be translated into practice.

Real-world treatment patterns for patients with newly diagnosed multiple myeloma in Alberta, Canada.

The purpose of this study is to describe the real-world multiple myeloma (MM) population in Alberta by examining patient/clinical characteristics and the treatment landscape. A retrospective, observational study was conducted using province-wide, administrative health data from Alberta, Canada evaluating newly diagnosed MM (NDMM) patients. Between 1 April 2011 and 31 March 2017, 1377 treated NDMM cases were identified. Of those, 328 (23.8%) received an autologous stem cell transplant (ASCT) within the first year of diagnosis. In the ASCT group, 189 advanced to second-line (57.6%), 103 (32.6%) to third-line and 97 (29.5%) had four or more lines of therapy. In non-ASCT patients, 553 (52.7%) advanced to second-line, 238 (22.7%) to third-line, and 154 (14.7%) had 4 or more lines of therapy. We observed a significant treatment attrition rate in NDMM. Therefore, the use of best therapy upfront and novel strategies aiming to decrease attrition rates in MM is encouraged.

Fluoridation cessation and oral health equity: a 7-year post-cessation study of Grade 2 schoolchildren in Alberta, Canada.

OBJECTIVE: Community water fluoridation, because of its universal scope and passive mechanism of uptake, is one component of a multifaceted approach to promoting equity in dental health. The objective of this study was to examine social inequities in children's dental health in the Canadian cities of Calgary (fluoridation cessation in 2011) and Edmonton (still fluoridated). METHODS: We analyzed data from surveys of population-based samples of Grade 2 (approx. age 7) children in Calgary in 2009/2010 (pre-cessation; n=557) and in both Calgary and Edmonton in 2013/2014 (Calgary, n=3230; Edmonton, n=2304) and 2018/2019 (Calgary, n=2649; Edmonton, n=2600) (post-cessation). We estimated associations between several socioeconomic indicators and dental caries indicators (i.e., dental caries experience [deft, DMFT] and untreated decay in two or more teeth [untreated decay]) using zero-inflated Poisson, binary logistic regression, and the concentration index of inequality. We compared those associations over time (between survey waves) and between cities at post-cessation. RESULTS: Persistent social inequities in deft and untreated decay were evident; for example, having no dental insurance was significantly associated with higher odds of untreated decay across city and survey wave. In most (but not all) cases, differences between cities and survey waves were consistent with an adverse effect of fluoridation cessation on dental health inequities. For example, the association between no dental insurance and higher odds of untreated decay in Calgary was greater in 2018/2019 (later post-cessation) than in 2009/2010 (pre-cessation; odds ratio [OR] for comparison of coefficients = 1.89 [1.36-2.63], p<0.001) and 2013/2014 (early post-cessation; OR for comparison of coefficients = 1.67 [1.22-2.28], p=0.001); that same association in 2018/2019 was greater in Calgary (fluoridation cessation) than in Edmonton (still fluoridated) (OR for comparison of coefficients = 1.44 [1.03-2.02], p=0.033). CONCLUSION: Social inequities in dental caries were present in both Calgary and Edmonton. Those inequities tended to be worse in Calgary where fluoridation was ceased. Our findings may be relevant to other settings where income inequality is high, dental services are costly, and dental public health infrastructure is limited.

RéSUMé: OBJECTIF: En raison de sa portée universelle et de son mécanisme de réception passif, la fluoration de l'eau des communautés s'inscrit dans une démarche multidimensionnelle de promotion de l'équité en santé dentaire. Notre étude visait à examiner les iniquités sociales en santé dentaire chez les enfants dans les villes canadiennes de Calgary (où la fluoration a cessé en 2011) et d'Edmonton (où l'eau est encore enrichie en fluor). MéTHODE: Nous avons analysé les données d'enquêtes menées auprès d'échantillons populationnels d'élèves de 2e année (environ 7 ans) à Calgary en 2009-2010 (avant l'arrêt; n = 557), et à Calgary et Edmonton en 2013-2014 (Calgary, n = 3 230; Edmonton, n = 2 304) et en 2018-2019 (Calgary, n = 2 649; Edmonton, n = 2 600) (après l'arrêt). Nous avons estimé les associations entre plusieurs indicateurs socioéconomiques et indicateurs de caries dentaires (c.-à-d. l'expérience de caries dentaires [dceo, DCMO] et de dégradation non traitée dans deux dents ou plus [dégradation non traitée]) à l'aide de la régression de Poisson à surreprésentation de zéros, de la régression logistique binaire et de l'indice de concentration des inégalités. Nous avons comparé ces associations dans le temps (entre les cycles de l'enquête) et entre les deux villes après l'arrêt de la fluoration. RéSULTATS: Des iniquités sociales persistantes selon l'indice dceo [dents cariées, extraites et obturées] et la dégradation non traitée étaient manifestes; par exemple, l'absence d'assurance dentaire présentait une corrélation significative avec une probabilité accrue de dégradation non traitée d'une ville à l'autre et d'un cycle à l'autre de l'enquête. Dans la plupart des cas (mais pas tous), les différences entre les villes et entre les cycles de l'enquête correspondaient à un effet indésirable de l'arrêt de la fluoration sur les iniquités en santé dentaire. Par exemple, l'association entre l'absence d'assurance dentaire et la probabilité accrue de dégradation non traitée à Calgary était plus importante en 2018-2019 (longtemps après l'arrêt) qu'en 2009-2010 (avant l'arrêt; rapport de cotes [RC] pour comparaison des coefficients = 1,89 [1,36-2,63], p < 0,001) et qu'en 2013-2014 (peu après l'arrêt; RC pour comparaison des coefficients = 1,67 [1,22-2,28], p = 0,001); cette même association en 2018-2019 était plus importante à Calgary (où la fluoration a cessé) qu'à Edmonton (où l'eau est encore enrichie en fluor) (RC pour comparaison des coefficients = 1,44 [1,03-2,02], p = 0,033). CONCLUSION: Des iniquités sociales relativement aux caries dentaires étaient présentes tant à Calgary qu'à Edmonton. Ces iniquités avaient tendance à être plus importantes à Calgary, où la fluoration a cessé. Nos constatations pourraient être pertinentes dans les autres endroits où l'inégalité des revenus est élevée, où les soins dentaires coûtent cher et où les infrastructures en santé publique dentaire sont limitées.

Fluoridation cessation and children's dental caries: A 7-year follow-up evaluation of Grade 2 schoolchildren in Calgary and Edmonton, Canada.

OBJECTIVES: We examined the effect of fluoridation cessation on children's dental caries experience in the Canadian cities of Calgary (cessation in 2011) and Edmonton (still fluoridated). METHODS: We used a pre-post cross-sectional design with comparison group. We studied Grade 2 schoolchildren (approximately 7 years old) 7-8 years after fluoridation cessation in Calgary, thus capturing children born after cessation occurred. Data collection included a dental examination conducted in school by calibrated dental hygienists, a questionnaire completed by parents, and fingernail clippings for a small subsample. Our overall analytic approach was twofold. We first examined differences in dental caries experience (deft and DMFT, and smooth surface caries based on defs and DMFS) between Calgary and Edmonton and over time (comparing 2018/2019 data to pre-cessation and early post-cessation surveys in our setting). Second, we evaluated whether differences were likely to reflect fluoridation cessation in Calgary, rather than other factors. RESULTS: The prevalence of caries in the primary dentition was significantly higher (P < .05) in Calgary (fluoridation cessation) than in Edmonton (still fluoridated). For example, crude deft prevalence in 2018/2019 was 64.8% (95% CI 62.3-67.3), n = 2649 in Calgary and 55.1% (95% CI 52.3-57.8), n = 2600 in Edmonton. These differences were consistent and robust: they persisted with adjustment for potential confounders and in the subset of respondents who were lifelong residents and reported usually drinking tap water; they had widened over time since cessation; and they were corroborated by assessments of dental fluorosis and estimates of total fluoride intake from fingernail clippings. Findings for permanent teeth were less consistent, which likely reflects that 7-year-olds have not had the time to accumulate enough permanent dentition caries experience for differences to have become apparent. CONCLUSIONS: Our findings are consistent with an adverse impact of fluoridation cessation on children's dental health in Calgary and point to the need for universal, publicly funded prevention activities-including but not limited to fluoridation.

Implementing an exercise oncology model to reach rural and remote individuals living with and beyond cancer: a hybrid effectiveness-implementation protocol for project EXCEL (EXercise for Cancer to Enhance Living Well).

INTRODUCTION: Individuals living with and beyond cancer from rural and remote areas lack accessibility to supportive cancer care resources compared with those in urban areas. Exercise is an evidence-based intervention that is a safe and effective supportive cancer care resource, improving physical fitness and function, well-being and quality of life. Thus, it is imperative that exercise oncology programs are accessible for all individuals living with cancer, regardless of geographical location. To improve accessibility to exercise oncology programs, we have designed the EXercise for Cancer to Enhance Living Well (EXCEL) study. METHODS AND ANALYSIS: EXCEL is a hybrid effectiveness-implementation study. Exercise-based oncology knowledge from clinical exercise physiologists supports healthcare professionals and community-based qualified exercise professionals, facilitating exercise oncology education, referrals and programming. Recruitment began in September 2020 and will continue for 5 years with the goal to enroll ~1500 individuals from rural and remote areas. All tumour groups are eligible, and participants must be 18 years or older. Participants take part in a 12-week multimodal progressive exercise intervention currently being delivered online. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework is used to determine the impact of EXCEL at participant and institutional levels. Physical activity, functional fitness and patient-reported outcomes are assessed at baseline and 12-week time points of the EXCEL exercise intervention. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of Alberta. Our team will disseminate EXCEL information through quarterly newsletters to stakeholders, including participants, qualified exercise professionals, healthcare professionals and community networks. Ongoing outreach includes community presentations (eg, support groups, fitness companies) that provide study updates and exercise resources. Our team will publish manuscripts and present at conferences on EXCEL's ongoing implementation efforts across the 5-year study. TRIAL REGISTRATION NUMBER: NCT04478851.