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Rationale: Clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Yet, practice is slow to change, evidenced by the little amount of walking activity in stroke rehabilitation units. Our recent study (n = 75) found that a structured, progressive protocol integrated with typical daily physical therapy improved walking and quality-of-life measures over usual care. Research therapists progressed the intensity of exercise by using heart rate and step counters worn by the participants with stroke during therapy. To have the greatest impact, our next step is to undertake an implementation trial to change practice across stroke units where we enable the entire unit to use the protocol as part of standard of care. Aims: What is the effect of introducing structured, progressive exercise (termed the Walk ’n Watch protocol) to the standard of care on the primary outcome of walking in adult participants with stroke over the hospital inpatient rehabilitation period? Secondary outcomes will be evaluated and include quality of life. Methods and sample size estimates: This national, multisite clinical trial will randomize 12 sites using a stepped-wedge design where each site will be randomized to deliver Usual Care initially for 4, 8, 12, or 16 months (three sites for each duration). Then, each site will switch to the Walk ’n Watch phase for the remaining duration of a total 20-month enrolment period. Each participant will be exposed to either Usual Care or Walk ’n Watch. The trial will enroll a total of 195 participants with stroke to achieve a power of 80% with a Type I error rate of 5%, allowing for 20% dropout. Participants will be medically stable adults post-stroke and able to take five steps with a maximum physical assistance from one therapist. The Walk ’n Watch protocol focuses on completing a minimum of 30 min of weight-bearing, walking-related activities (at the physical therapists’ discretion) that progressively increase in intensity informed by activity trackers measuring heart rate and step number. Study outcome(s): The primary outcome will be the change in walking endurance, measured by the 6-Minute Walk Test, from baseline (T1) to 4 weeks (T2). This change will be compared across Usual Care and Walk ’n Watch phases using a linear mixed-effects model. Additional physical, cognitive, and quality of life outcomes will be measured at T1, T2, and 12 months post-stroke (T3) by a blinded assessor. Discussion: The implementation of stepped-wedge cluster-randomized trial enables the protocol to be tested under real-world conditions, involving all clinicians on the unit. It will result in all sites and all clinicians on the unit to gain expertise in protocol delivery. Hence, a deliberate outcome of the trial is facilitating changes in best practice to improve outcomes for participants with stroke in the trial and for the many participants with stroke admitted after the trial ends.

Background The COVID-19 pandemic has led to increased utilization of telemedicine services. Methods A retrospective analysis of all non-hospital-based medical healthcare services in Ontario from November 2019 to June 2021 was collected from the Ontario Health Insurance Plan (OHIP) billing database. Only fee-for-service billings were included in the present analysis. Coincident COVID-19 cases were obtained from Public Health Ontario. Comparisons were made based on age bracket, sex, telemedicine and in-person care. Results Billings for telemedicine services in Ontario increased from $1.7 million in November 2019 to $64 million in April 2020 and the proportions reached a mean peak of 72% in April 2020 and declined to 46% in June 2021. A positive correlation was found between the use of telemedicine and COVID-19 cases (p = 0.05). The age group with the highest proportion of telemedicine use was the 10–20-year-olds, followed by the 20–50-year-olds (61 ± 9.0%, 55 ± 7.3%, p = 0.01). Both age groups remained above 50% telemedicine services at the end of the study period. There is a persistent sex preference for females to adopt telemedicine (females 54.2 ± 8.0%, males 47.9 ± 7.7%, ANCOVA p = 0.05) Conclusions The use of telemedicine services remains at a high level across groups, particularly the 10–50-year-olds. There are clear age and sex preferences for using telemedicine. Studying these differences may provide insights into how the delivery of non-hospital-based medicine has changed during the COVID-19 pandemic.

BACKGROUND. Large scale clinical hormone replacement therapy [HRT] studies have yielded conflicting breast cancer [BrCa] outcomes. The studies reviewed include:. Two Non-Randomized Studies [Non-RS], based on either estrogen+progestin Provera [E+P HRT]; or estrogen-alone [E-HRT]:. 1. Collaborative Group Meta-analysis of 58 HRT studies [CG-M] [1]. 2. Million Women Study [MWS] [2]. Two Randomized Studies [RS] - the Women’s Health Initiative [WHI] Trials 1 and 2:. 1. WHI HRT Trial 1 - based on E+P HRT [3] 2. WHI HRT Trial 2 - based on E-HRT [3]. Of all the above HRT studies, only the WHI HRT Trial 2 showed long-term reductions in Breast Cancer Incidence [BrCa-I] and Mortality [BrCa-M], while all others showed varying degrees of BrCa harms. OBJECTIVES. To evaluate differences between the representative HRT studies, their results and conclusions. METHODOLOGY. Compared were BrCa outcomes:. i. Between the two the RS - WHI HRT Trial 2 vs. 1 (Analysis 1) ii. E-HRT impact from a RS [i.e., the WHI HRT Trial 2] vs. Non-RS [the CG-M/MWS] (Analysis 2). For both analyses, risk ratios (RR) for BrCa-I & BrCa-M, and the corresponding 95% confidence intervals (CI), were obtained from the studies [RR1 and RR2, respectively]. Subsequently, the ratio of “risk ratios” (R-RRs), were estimated, in each analysis, separately for BrCa-I and BrCa-M. The 95% confidence intervals and p-values for the R-RRs were derived through logarithmic transformation of the risk ratios and 95% CI originally reported. RESULTS. CONCLUSIONS.. Based on these outcomes, the following emerging HRT paradigms can be considered:. PARADIGM 1: The addition of Progestin Provera abrogates the benefits of E-alone HRT [4]. PARADIGM 2: Considering the presence of many confounding factors in non-randomized HRT studies [e.g., selection bias, with more high-risk women receiving HRT (5)], the reduction of BrCa-I and BrCa-M rates observed in the WHI Trial 2 has to be accepted as the least biased conclusion of the E-HRT impact on breast cancer. PARADIGM 3: The mechanism of the E-alone based HRT breast cancer benefit could be explained by the Estrogen Duality [endogenous estrogen remaining breast carcinogenic, while the exogenous estrogen emerging breast cancer suppressive] - a concept articulated already in 2010 [6], now confirmed in the WHI HRT Trial 2 final outcomes, and in these analyses. REFERENCES. 1. Collaborative Group on Hormonal Factors in Breast Cancer. The Lancet, 2019; vol. 394(1024). 2. Beral V et al. The Lancet, 2019; vol. 394. 3. Chlebowski R et al. JAMA, 2020; vol. 324(4). 4. Ragaz J et al. AACR, 2019; vol. 79(4) Supplement. 5. Shapiro S et al. J Fam Plann Reprod Health Care, 2013; vol. 39(2). 6. Ragaz J et al. Ca Res, 2010; vol. 70(24) Supplement. Analysis 1: RS WHI Trial 2 vs. 1 [ 3]RS - RRs: E-HRT vs. Placebo. RR1 [95% C.I.]RS - RRs: E+P HRT vs. Placebo. RR2 [95% C.I.]Ratio of “Risk Ratios” [R-RRs]PBrCa Incidence0.78 [0.65-0.93]1.28 [1.13-1.45]0.61 [0.49-0.76] Citation Format: Joseph Ragaz, John J Spinelli, Hong Qian, Hubert Wong, Shayan Shakeraneh, Joel Fox, Kenneth S Wilson. Estrogen and breast cancer benefits: Emerging hormone replacement therapy breast cancer paradigms [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-03.

Background Insertion of a central venous access device (CVAD) allows clinicians to easily access the circulation of a patient to administer life-saving interventions. Due to their invasive nature, CVADs are prone to complications such as bacterial biofilm production and colonization, catheter-related bloodstream infection, occlusion, and catheter-related venous thrombosis. A CVAD is among the most common interventions for patients in the intensive care unit (ICU), exposing this vulnerable population to the risk of nosocomial infection and catheter occlusion. The current standard of care involves the use of normal saline as a catheter locking solution for central venous catheters (CVCs) and peripherally inserted central catheter (PICC) lines, and a citrate lock for hemodialysis catheters. Saline offers little prophylactic measures against catheter complications. Four percent of tetrasodium ethylenediaminetetraacetic acid (EDTA) fluid (marketed as KiteLock Sterile Locking Solution™) is non-antibiotic, possesses antimicrobial, anti-biofilm, and anti-coagulant properties, and is approved by Health Canada as a catheter locking solution. As such, it may be a superior CVAD locking solution than the present standard of care lock in the ICU patient population. Methods Our team proposes to fill this knowledge gap by performing a multi-center, cluster-randomized, crossover trial evaluating the impact of 4% tetrasodium EDTA on a primary composite outcome of the incidence rate of central line-associated bloodstream infection (CLABSI), catheter occlusion leading to removal, and use of alteplase to resolve catheter occlusion compared to the standard of care. The study will be performed at five critical care units. Discussion If successful, the results of this study can serve as evidence for a shift of standard of care practices to include EDTA locking fluid in routine CVAD locking procedures. Completion of this study has the potential to improve CVAD standard of care to become safer for patients, as well as provides an opportunity to decrease strain on healthcare budgets related to treating preventable CVAD complications. Success and subsequent implementation of this intervention in the ICU may also be extrapolated to other patient populations with heavy CVAD use including hemodialysis, oncology, parenteral nutrition, and pediatric patient populations. On a global scale, eradicating biofilm produced by antibiotic-resistant bacteria may serve to lessen the threat of “superbugs” and contribute to international initiatives supporting the termination of antibiotic overuse. Trial registration ClinicalTrials.gov NCT04548713, registered on September 9th, 2020.

We investigated cardiovascular disease (CVD) risk associated with latent tuberculosis infection (LTBI) (Aim-1) and LTBI therapy (Aim-2) in British Columbia, a low-tuberculosis-incidence setting. 49,197 participants had valid LTBI test results. Cox proportional hazards model was fitted, adjusting for potential confounders. Compared with the participants who tested LTBI negative, LTBI positive was associated with an 8% higher CVD risk in complete case data (adjusted hazard ratio (HR): 1.08, 95% CI: 0.99-1.18), a statistically significant 11% higher risk when missing confounder values were imputed using multiple imputation (HR: 1.11, 95% CI: 1.02-1.20), and 10% higher risk when additional proxy variables supplementing known unmeasured confounders were incorporated in the highdimensional disease risk score technique to reduce residual confounding (HR: 1.10, 95% CI: 1.01-1.20). Also, compared with participants who tested negative, CVD risk was 27% higher among people who were LTBI positive but incomplete LTBI therapy (HR: 1.27, 95% CI: 1.04-1.55), whereas the risk was similar in people who completed LTBI therapy (HR: 1.04, 95% CI: 0.87-1.24). Findings were consistent in different sensitivity analyses. We concluded that LTBI is associated with an increased CVD risk in low-tuberculosis-incidence settings, with a higher risk associated with incomplete LTBI therapy and attenuated risk when therapy is completed.

Study objective We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. Methods We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events. Results Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]). Conclusion In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.

Blood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.We did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15-49 years (12-49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP]120 mm Hg and diastolic blood pressure [dBP]80 mm Hg), elevated blood pressure (sBP 120-129 mm Hg and dBP80 mm Hg), stage 1 hypertension (sBP 130-139 mm Hg or dBP 80-89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140-159 mm Hg or dBP 90-109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.Between Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29-5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65-11·07]) and perinatal death (5·07 [3·64-7·07]), particularly stillbirth (8·53 [5·63-12·92]).In low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.University of British Columbia, the BillMelinda Gates Foundation.

BACKGROUND: End-stage ankle arthritis has long been managed surgically with open ankle arthrodesis (OAA). Since the first published report in 1983, arthroscopic ankle arthrodesis (AAA) has been thought to be associated with improved patient-reported outcome measures (PROMs) and fewer complications. The purpose of the present study was to compare the long-term PROMs, major complications, and reoperations for these 2 approaches at up to 15 years of follow-up.METHODS: This longitudinal cohort study included patients at our institution who underwent primary ankle arthrodesis for the treatment of end-stage arthritis. Demographic data and preoperative COFAS (Canadian Orthopaedic Foot and Ankle Society) ankle arthritis type were collected for all patients. PROMs were completed preoperatively, at 6 months, and annually thereafter to 5 years. PROMs were compared at all time points with use of a mixed-effects regression model that adjusted for preoperative variables and scores. Major complications and reoperations at the site of the ankle arthrodesis were also compared.RESULTS: Of 1,294 patients who were screened for inclusion, 351 who had undergone ankle arthrodesis between 2003 and 2019 were eligible for the study. Of those, 223 had undergone AAA and 128 had undergone OAA. The 2 groups were similar preoperatively with respect to demographics, but COFAS Type-4 arthritis was relatively more common in the OAA group and Type-1 arthritis was relatively more common in the AAA group. In addition, the Ankle Osteoarthritis Scale (AOS) score and Ankle Arthritis Score (AAS) were better in the AAA group. In the mixed-effects model analysis, the differences in postoperative outcome scores between the groups were not significant. The risk of revision due to malunion or nonunion was similar in both groups (6% in the AAA group, compared with 4% in the OAA group). Deep infection and wound complications did not occur in the arthroscopic group but occurred in 4% of the patients in the OAA group.CONCLUSIONS: After adjustment for baseline patient characteristics, there were no differences in PROMs between the 2 techniques. Ankle arthrodeses done arthroscopically had a similar revision rate but lower infection rate compared with those done with the open technique.LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background In a cross-sectional stepped-wedge cluster randomized trial comparing usual care to a new intervention, treatment allocation and time are correlated by design because participants enrolled early in the trial predominantly receive usual care while those enrolled late in the trial predominantly receive the new intervention. Current guidelines recommend adjustment for time effects when analyzing stepped-wedge cluster randomized trials to remove the confounding bias induced by this correlation. However, adjustment for time effects impacts study power. Within the Frequentist framework, adopting a sample size calculation that includes time effects would ensure the trial having adequate power regardless of the magnitude of the effect of time on the outcome. But if in fact time effects were negligible, this would overestimate the required sample size and could lead to the trial being deemed infeasible due to cost or unavailability of the required numbers of clusters or participants. In this study, we explore the use of prior information on time effects to potentially reduce the required sample size of the trial. Methods We applied a Bayesian approach to incorporate the prior information on the time effects into cluster-level statistical models (for continuous, binary, or count outcomes) for the stepped-wedge cluster randomized trial. We conducted simulations to illustrate how the bias in the intervention effect estimate and the trial power vary as a function of the prior precision and the mis-specification of the prior means of the time effects in an example scenario. Results When a nearly flat prior for the time effects was used, the power or sample size calculated using the Bayesian approach matched the result obtained using the Frequentist approach with time effects included. When a highly precise prior for the time effects (with accurately specified prior means) was used, the Bayesian result matched the Frequentist result obtained with time effects excluded. When the prior means of the time effects were nearly correctly specified, including this information improved the efficiency of the trial with little bias introduced into the intervention effect estimate. When the prior means of the time effects were greatly mis-specified and a precise prior was used, this bias was substantial. Conclusion Including prior information on time effects using a Bayesian approach may substantially reduce the required sample size. When the prior can be justified, results from applying this approach could support the conduct of a trial, which would be deemed infeasible if based on the larger sample size obtained using a Frequentist calculation. Caution is warranted as biased intervention effect estimates may arise when the prior distribution for the time effects is concentrated far from their true values.

Background: Administrative databases do not contain Body Mass Index (BMI) informa- tion. In proportion-based imputation (PBI) technique, a BMI category is assigned to an individual according to the proportions observed in external survey data. Alternatively, BMI can be imputed using Multiple Imputation (MI). Objectives: To compare MI with PBI to impute BMI variable in osteoarthritis (OA)- cardiovascular disease (CVD) relationship. Research Design: plasmode simulation study. Subjects: used publicly available data from the Canadian Community Health Survey (CCHS) cycles 1.1, 2.1, and 3.1. Measures: BMI was set missing for everyone in the 500 simulated data created from CCHS 3.1 data. Dataset compiled from CCHS cycles 1.1 and 2.1 served as the external data (BMI observed). BMI missing in copies of simulated data was imputed using MI and PBI accessing observed BMI information in external data. After imputation, distribution of BMI variable and the adjusted odds ratio (aOR) estimated from multivariable logistic regression model were compared. Results: Compared to PBI, MI produced proportions of individuals closer to the known proportions across the BMI categories except for the overweight category. Considering the known aOR of 1.59 (1.36, 1.82), BMI imputed using MI introduced less bias in OA- CVD association compared to PBI, the aOR was 1.62 (1.39, 1.86) and 1.66 (1.41, 1.90), respectively. Conclusions: This is the first study to compare MI with PBI in the context of imputing BMI information that is not recorded at the database level. MI was superior to imputation method based on population-level proportions in imputing BMI missing for everyone in the simulated datasets.

Summary Background To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. Methods In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014–17. Consenting pregnant women, aged 12–49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. Findings Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22–30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90–1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community treatment with methyldopa (one [2%] of 51; India only) and none occurred after in-community treatment with magnesium sulfate or during transport to facility. Interpretation The CLIP intervention did not reduce adverse pregnancy outcomes. Future community-level interventions should expand the community health worker workforce, assess general (rather than condition-specific) messaging, and include health system strengthening. Funding University of British Columbia, a grantee of the Bill & Melinda Gates Foundation.

STUDY OBJECTIVES: Intensive care unit nurses commonly work multiple consecutive 12-hour shifts that leave little time for sleep between work shifts. Working multiple consecutive shifts could compromise vigilance and patient care, especially with respect to managing high-risk medications such as insulin infusions. We hypothesized that as the number of consecutive shifts worked by nurses increases, the rate of hypoglycemia in patients who are receiving an insulin infusion would also increase. METHODS: We identified patients who had hypoglycemia (glucose ≤ 3.5 mmol/L, 63 mg/dL) between December 2008 and December 2009 in 3 intensive care units in Vancouver, British Columbia, Canada. For each hypoglycemic event, we counted the number of shifts worked on consecutive days during the previous 72 hours by the bedside nurse who was caring for the patient at the time of hypoglycemia (case shift). For each case shift, we identified up to 3 control shifts (24, 48, and 72 hours before the hypoglycemic event in the same patient when there were no hypoglycemic events) and counted the number of consecutive shifts worked by those nurses in the previous 72 hours. This analysis allowed us to control for patient-associated confounders. Conditional logistic regression was used to determine the association between number of consecutive shifts worked and occurrence of hypoglycemic events. RESULTS: A total of 282 hypoglycemic events were identified in 259 patients. For 191 events, we were able to identify 1 or more control shifts. Compared with nurses who had not worked a shift in the preceding day, the odds ratio of a hypoglycemic event was 1.68 (95% confidence interval: 1.12–2.52), 2.16 (95% confidence interval:1.25–3.73), and 2.54 (95% confidence interval: 1.28–5.06) for nurses who were working their second, third, or fourth consecutive shift, respectively. CONCLUSIONS: Working multiple consecutive nursing shifts is associated with increased risk of hypoglycemic events in patients in an intensive care unit. CITATION: Ayas NT, Jeklin A, Tholin H, et al. Consecutive nursing shifts and the risk of hypoglycemia in critically ill patients who are receiving intravenous insulin: a multicenter study. J Clin Sleep Med. 2020;16(6):949–953.

Highlights • As implemented, the CLIP intervention did not improve the primary composite outcome. • ASHAs and ANMs were able to undertake all aspects of the mobile health app-guided visits. • Women could not be reached in their communities as frequently as planned. • Eight or more POM-guided contacts were associated with fewer stillbirths supporting WHO guidance. • Community-level interventions are unlikely to improve outcomes without enhanced facility care., Objectives Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. Study design The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (

Supplemental Digital Content is available in the text., In pregnancy in well-resourced settings, limited data suggest that higher blood pressure (BP) visit-to-visit variability may be associated with adverse pregnancy outcomes. Included were pregnant women in 22 intervention clusters of the CLIP (Community-Level Interventions for Preeclampsia) cluster randomized trials, who had received at least 2 prenatal contacts from a community health worker, including standardized BP measurement. Mixed-effects adjusted logistic regression assessed relationships between pregnancy outcomes and both BP level (median [interquartile range]) and visit-to-visit variability (SD and average real variability [ARV], adjusted for BP level), among all women and those who became hypertensive. The primary outcome was the CLIP composite of maternal and perinatal mortality and morbidity. Among 17 770 pregnancies, higher systolic and diastolic BP levels were associated with increased odds of the composite outcome per 5 mm Hg increase in BP (odds ratio [OR], 1.05 [95% CI, 1.03–1.07] and OR, 1.08 [1.06–1.11], respectively). Higher BP visit-to-visit variability was associated with increased odds, per a SD increase in BP variability measure, of (1) hypertension (systolic: OR, 2.09 [1.98–2.21] for SD and 1.52 [1.45–1.60] for ARV; diastolic: OR, 2.70 [2.54–2.87] for SD and 1.86 [1.76–1.96] for ARV); and (2) the composite outcome (systolic: OR, 1.10 [1.06–1.14] for SD and 1.06 [1.02–1.10] for ARV; diastolic: OR, 1.07 [1.03–1.11] for SD and 1.06 [1.02–1.09] for ARV). In 3 less-developed countries, higher BP level and visit-to-visit variability predicted adverse pregnancy outcomes, providing an opportunity for high-definition medicine.

BACKGROUND Heart failure (HF) is a costly health condition and a major public health problem. It is estimated that 2%-3% of the population in developed countries has HF, and the prevalence increases to 8% among patients aged ≥75 years. Home telemonitoring is a form of noninvasive, remote patient monitoring that aims to improve the care and management of patients with chronic HF. Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring (TEC4Home) is a project that implements and evaluates a comprehensive home monitoring protocol designed to support patients with HF as they transition from the emergency department to home. OBJECTIVE The aim of this study is to assess the cost of using the home monitoring platform (TEC4Home) relative to usual care for patients with HF. METHODS This study is a cost-consequence analysis of the TEC4Home pilot study. The analysis was conducted from a partial societal perspective, including direct and indirect health care costs. The aim is to assess the costs of the home monitoring platform relative to usual care and track costs related to health care utilization during the 90-day postdischarge period. RESULTS Economic analysis of the TEC4Home pilot study showed a positive trend in cost savings for patients using TEC4Home. From both the health system perspective (Pre TEC4Home cost per patient: CAD $2924 vs post TEC4Home cost per patient: CAD $1293; P=.01) and partial societal perspective (Pre TEC4Home cost per patient: CAD $2411 vs post TEC4Home cost per patient: CAD $1108; P=.01), we observed a statistically significant cost saving per patient. CONCLUSIONS In line with the advantages of conducting an economic analysis alongside a feasibility study, the economic analysis of the TEC4Home pilot study facilitated the piloting of patient questionnaires and informed the methodology for a full clinical trial.

Background Heart failure (HF) is a costly health condition and a major public health problem. It is estimated that 2%-3% of the population in developed countries has HF, and the prevalence increases to 8% among patients aged ≥75 years. Home telemonitoring is a form of noninvasive, remote patient monitoring that aims to improve the care and management of patients with chronic HF. Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring (TEC4Home) is a project that implements and evaluates a comprehensive home monitoring protocol designed to support patients with HF as they transition from the emergency department to home. Objective The aim of this study is to assess the cost of using the home monitoring platform (TEC4Home) relative to usual care for patients with HF. Methods This study is a cost-consequence analysis of the TEC4Home pilot study. The analysis was conducted from a partial societal perspective, including direct and indirect health care costs. The aim is to assess the costs of the home monitoring platform relative to usual care and track costs related to health care utilization during the 90-day postdischarge period. Results Economic analysis of the TEC4Home pilot study showed a positive trend in cost savings for patients using TEC4Home. From both the health system perspective (Pre TEC4Home cost per patient: CAD $2924 vs post TEC4Home cost per patient: CAD $1293; P=.01) and partial societal perspective (Pre TEC4Home cost per patient: CAD $2411 vs post TEC4Home cost per patient: CAD $1108; P=.01), we observed a statistically significant cost saving per patient. Conclusions In line with the advantages of conducting an economic analysis alongside a feasibility study, the economic analysis of the TEC4Home pilot study facilitated the piloting of patient questionnaires and informed the methodology for a full clinical trial.

Purpose To examine the association between moral distress in ICU personnel, and medication errors and adverse events, and other adverse events. Materials and methods In 13 ICUs, we measured moral distress once in all ICU staff, and incidence of five explicity-defined adverse safety events over 2 years. In 10 of the ICUs, pharmacists tabulated medication errors and adverse events during 1 day in the 2-year period. Average moral distress scores for each professional group were correlated with each safety measure. Results In the pharmacy study, there were almost no significant correlations between moral distress and measures of medication safety. However, higher moral distress in nurses was associated with more interceptions of near misses per administration error ( r = 0.68, p = 0.04), and higher moral distress in physicians was associated with more incorrect measurements for medication monitoring per recommended action for monitoring ( r = 0.68, p = 0.03). For the other adverse events, the only significant association was a positive association between moral distress in physicians and bleeding while on anticoagulants (OR: 1.1; 95% CI: 1.0–1.3). Conclusion Moral distress in ICU personnel is generally not associated with medication errors or adverse events, or other adverse events, but it may be associated with both hyper-vigilance and distraction.

Objective Radiographic measurements of the alpha angle and the lateral center edge (LCE) angle in the hip joint are important for the diagnosis of femoroacetabular syndrome, a potential risk factor for hip osteoarthritis. Our objective was to determine whether these measurements are associated with hip-related patient-reported outcomes in young and middle-aged individuals. Methods A stratified random sample of white men and women ages 20-49 years, with and without hip pain, was selected using random digit dialing from the population of metro Vancouver, Canada. The alpha and LCE angles were measured bilaterally on radiographs using Dunn and anteroposterior views, respectively. Patient-reported outcomes were measured by the Copenhagen Hip And Groin Outcome Score (HAGOS), which has scales for symptoms, pain, daily activities, sports, physical activity, and quality of life (QoL). We performed descriptive analyses and a regression analysis with restricted cubic splines, adjusted for age and sex and weighted for the sampling design. Results Data were obtained for 500 subjects. The alpha angle distribution was strongly skewed, with a mean of 54°. The LCE angle distribution was symmetric, with a mean of 34°. In the restricted cubic splines analysis, the relationship between the alpha angle and HAGOS scores was nonlinear, with higher alpha angles generally associated with worse HAGOS scores for alpha >60°. The associations were statistically significant for symptoms, sports, and QoL. No association was found between the LCE angle and HAGOS scales. Conclusion In a general population sample ages 20-49 years, we have found an association between the alpha angle and hip-related patient-reported outcomes.

Purpose To assess the association between moral distress and general workplace distress in intensive care unit (ICU) personnel. Materials and methods We administered the Moral Distress Scale Revised and the Job Content Questionnaire to all clinicians (870 nurses, 68 physicians, 452 other health professionals) in 13 ICUs (3 tertiary, 3 large community, 7 small community) in British Columbia, Canada. We used mixed effects regression, treating ICUs as clusters, to examine the association between the Moral Distress Score and each Job Content Questionnaire scale (decision latitude, psychological stressors, social support, psychological strain) after adjusting for age, sex, and years of experience of respondents; separate analyses were done for each profession. Results Overall response rate was 45%. Nurses and other health professionals had higher moral distress scores than physicians, but there were no differences in general workplace distress scores among professional groups. After adjustment for demographic characteristics, higher moral distress in nurses was associated with lower decision latitude and social support, and with higher psychological stressors and psychological strain. For physicians and other professionals, these relationships were similar. Conclusions Moral distress is associated with general workplace distress in ICU personnel. Interventions that ameliorate either type of distress may also ameliorate the other.

Background Risperidone, an atypical antipsychotic medication, is recommended as a first line treatment for acute mania in patients with bipolar disorder I (BD I). It is unknown if continuing treatment with risperidone adjunct to lithium or valproate after remission of the manic episode offers additional benefit in prevention of mood episode relapse. Methods A post-hoc subgroup analysis was conducted using data from a 52-week, double-blind, placebo controlled trial involving 93 patients treated with oral risperidone adjunct to mood stabilizer, randomized to arms discontinuing risperidone at entry (“0-week arm”), 24 weeks after entry (“24-week arm”) or continuing risperidone (“52-week arm”). Time to any episode, manic episode, and depressive episode was compared between arms using Cox regression models. Results Time to any mood episode was longer in the 24-week arm versus the 0-week arm (HR: 0.57, 95% CI: 0.31–1.05, P = 0.07) and shorter in the 52-week arm versus 24-week arm (HR: 1.85, 95% CI: 1.00–3.41, P = 0.05), though these results were not significant. Time to relapse into manic episode was significantly longer in the 24-week arm versus 0-week arm (HR: 0.14, 95% CI: 0.03, 0.65, P = 0.01). No other significant differences were observed between arms. Limitations The sample size was modest, as the original dataset was powered to study optimal duration for two atypical antipsychotics. Conclusions Adjunctive risperidone treatment was observed to reduce the risk of manic episodes during the first 24 weeks, but not after 24 weeks. Treatment did not appear to reduce the risk of depressive episodes.

OBJECTIVE: To quantitate breast cancer incidence (BrCa-I) and mortality (BrCa-M) outcome differences between the two Women's Health Initiative (WHI) HRT trials,1,2 the ratio of hazards was calculated for estrogen-alone based hormone replacement therapy (E-HRT) vs. placebo (P), and E + progestin Provera (ProgProv) combination HRT vs. P trials. METHODS: Hazard ratios (HR) of BrCa-I and BrCa-M and 95% confidence intervals (CI) were obtained from both WHI HRT trials. Subsequently, to compare BrCa outcomes between E-HRT vs. E + ProgProv, the ratios of HRs between the trials (HR1/HR2) were estimated separately for i. BrCa-I all women, ii. BrCa-I low Gail score (Gail score RESULTS: Outcome Comparison, the two WHI HRT randomized trials. Ratio of Hazards, BrCa Incidence and BrCa mortality E-HRT vs. P, HR1 (95% CI)E-HRT + ProgProv vs. P, HR2 (95% CI)HR1/HR2 (95% CI)pBrCa-I All Woman10.77 (0.62-0.95)1.25 (1.07-1.46)0.62 (0.47-0.80)0.0004BrCa-I Low Gail Score* (Gail score CONCLUSIONS: Our calculations show that the different outcomes between the two WHI HRT trials, estimated as ratio of hazards, are highly significant on statistical basis, both for BrCa incidence and for BrCa mortality. These findings highlight the potential carcinogenic impact of ProgProv and the major public health benefits of HRT based on E alone. REFERENCES: 1. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. The Lancet Oncology 2012;13:476-86. 2. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA 2017;318:927-38. Citation Format: Ragaz J, Qian H, Wong H, Wilson KS, Shakeraneh S, Spinelli JJ. Estrogen-alone based hormone replacement therapy (HRT) reduces breast cancer (BrCa) incidence and mortality whereas estrogen plus progestin Provera based HRT increases both BrCa incidence and BrCa mortality: A comparative analysis of Women's Health Initiative trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-13-04.

OBJECTIVE: To compare, in the setting of breast cancer (BrCa) prevention, the impact of estrogen-based hormone replacement therapy (E-HRT) vs. tamoxifen (TAM) on breast cancer mortality (BrCa-M) and breast cancer case fatality ratio (BrCa-CFR), by analyzing data from the Women's Health Initiative Trial 2 (WHI HRT Trial 2, E-HRT vs. placebo [P])1 and the International Breast Cancer Intervention Study 1 (IBIS-1), TAM vs. P.2 METHODS: Hazard ratios (HR) and confidence intervals (CI) for BrCa incidence and mortality were extracted from the original WHI HRT Trial 2 and IBIS-1 trials.1,2 BrCa-CFRs were estimated by dividing the mortality HR by the incidence HR. Subsequently, to compare E-HRT vs. TAM outcomes, the ratios of HRs (HR1/HR2) between the two trials were estimated separately for BrCa-M and BrCa-CFR. The 95% CI was derived through logarithmic transformation of the 95% CI originally reported. RESULTS: Mortality and Case Fatality Outcomes: Impact of E-HRT versus TAM, expressed as ratio of HRs E-HRT vs. Placebo, HR1TAM vs. Placebo, HR2HR1/HR2pMortality0.55 (0.33-0.92)1.19 (0.68-2.10)0.46 (0.22-0.99)0.046Case Fatality0.70 (0.40-1.20)1.68 (0.93-3.01)0.42 (0.18-0.94)0.040 CONCLUSIONS: While acknowledging between-trial comparisons including eligibility differences, E-HRT yields significant reductions in BrCa mortality and case fatality as compared with TAM (54% and 58% respectively). These unexpected breast cancer mortality reductions represent major public health gains, additional to the already known superiority of E-HRT over TAM in terms of skeletal fracture rates and Alzheimer's dementia mortality reduction, and, in women entering menopause, also of cardiac and all-cause mortality reductions. REFERENCES: 1. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA 2017;318:927-38. 2. Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. The Lancet Oncology 2015;16:67-75. Citation Format: Ragaz J, Shakeraneh S, Qian H, Wilson KS, Wong H, Spinelli JJ. Estrogen-based hormone replacement [HRT] therapy is substantially more effective than tamoxifen in reducing breast cancer mortality and breast cancer case fatality ratio: Emergence of a new paradigm [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-13-06.

To determine the association of effusion detected by physical examination with the prevalence of bone marrow lesions (BMLs) on magnetic resonance imaging (MRI), and the incidence/progression of BMLs over 3 years in subjects with knee osteoarthritis.A population-based cohort with knee pain (n = 255) was assessed for effusion on physical examination. On MRI, BMLs were graded 0-3 (none, mild, moderate, severe), and incidence/progression was defined as a worsening of the sum of BML scores over 6 surfaces by ≥1 grade. We analyzed the full cohort and a mild disease subsample with a Kellgren/Lawrence (K/L) grade3. Cross-sectional logistic and longitudinal exponential regression analyses were performed, adjusted for age, sex, body mass index (BMI) and pain. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for effusion detected by physical examination versus BMLs (prevalence and incidence/progression).The weighted mean age was 56.7 years, the mean BMI was 26.5, 56.3% were women, 20.1% had effusion on physical examination, and 80.7% had a K/L grade3. Effusion on physical examination was significantly associated with prevalent BMLs in the full cohort (odds ratio [OR] 6.10 [95% confidence interval (95% CI) 2.77-13.44]) and in the K/L grade3 cohort (OR 6.88 [95% CI 2.76-17.15]). In the full cohort, sensitivity, specificity, PPV, and NPV were 34.6, 92.5, 79.9, and 62.1%, respectively, and in the K/L3 cohort 31.7, 94.0, 75.5, and 70.1%, respectively. Longitudinally, effusion on physical examination was not significantly associated with BML incidence/progression in the full cohort (hazard ratio [HR] 1.83 [95% CI 0.95-3.52]) or in the K/L grade3 cohort (HR 1.73 [95% CI 0.69-4.33]). In the two cohorts, sensitivity, specificity, PPV, and NPV were 32.0, 82.2, 42.2, and 74.9%, respectively, and 21.2, 85.6, 30.1, and 78.8% respectively.BMLs on MRI can be predicted from physical examination effusion cross-sectionally, with a high PPV of 79.9%. Assessment for knee effusion on physical examination is useful for determining potential candidates with BMLs before costly MRI screening for recruitment into clinical trials.