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Early identification of people with diabetes or prediabetes enables greater opportunities for glycemic control and management strategies to prevent related complications. To identify gaps in screening for these conditions, we examined population trends in receipt of timely glucose testing overall and in specific clinical subgroups.Using linked administrative databases, we conducted a retrospective cohort study of people aged 40 years and older without diabetes at baseline. Our primary outcome was up-to-date glucose testing, defined as having received testing at least once in the 3 years before each index year from 2010 to 2017, using linked administrative databases of people residing in Ontario, Canada. We calculated rates of up-to-date testing by age group, sex, ethnicity (South Asian, Chinese, general population) and comorbidities (hypertension, hyperlipidemia, cardiovascular disease).Over the 8-year study period, up-to-date glucose testing rates were stable at 67% for men and 77% for women (both relative risk 1.00 per year; 95% confidence interval 1.00-1.00). Testing rates were significantly lower in men than in women (all age groupsWe found lower glucose testing rates in younger men and people with hypertension. Our findings reinforce the need for initiatives to increase awareness of glycemic testing.

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was30 mm Hg with a pulmonary vascular resistance of300 dynes

The American journal of pathology 192(2), 239-253 (2022). doi:10.1016/j.ajpath.2021.10.020, Published by Elsevier, New York [u.a.]

Regular physical activity (PA) has been shown to improve glycemic control in persons with type 2 diabetes. This study aimed to investigate the impact of PA on blood glucose after controlling for medication use, demographics, and week of activation using a real-world population of individuals with type 2 diabetes. A longitudinal, retrospective study was performed evaluating weekly PA of Livongo members (N = 9,509), which analyzed fasting blood glucose (FBG), step counts, and daily active minutes. Linear mixed-effect modeling technique was used to investigate within member and between member effects of input variables on average weekly FBG. Of members enrolled, 6,336 (32%) had self-reported body mass index, qualified week with diabetes medications, and FBG measures. Members’ baseline average age was 49.4 (SD 10.1) years old, 43% female, and 45,496 member weeks with an average of 7.2 qualified weeks (PA observable in ≥4 days) per member. Average weekly FBG was 140.5 mg/dL (SD 39.8), and average daily step counts were 4,833 (SD 3,266). Moving from sedentary (

The Janus family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) play an essential role in the receptor signaling of cytokines that have been implicated in the pathogenesis of severe asthma, and there is emerging interest in the development of small-molecule-inhaled JAK inhibitors as treatments. Here, we describe the optimization of a quinazoline series of JAK inhibitors and the results of mouse lung pharmacokinetic (PK) studies where only low concentrations of parent compound were observed. Subsequent investigations revealed that the low exposure was due to metabolism by aldehyde oxidase (AO), so we sought to identify quinazolines that were not metabolized by AO. We found that specific substituents at the quinazoline 2-position prevented AO metabolism and this was rationalized through computational docking studies in the AO binding site, but they compromised kinome selectivity. Results presented here highlight that AO metabolism is a potential issue in the lung.

Young women in sub-Saharan Africa account for two-thirds of all new HIV infections and face high rates of unintended pregnancy. Multipurpose prevention technologies (MPTs) are promising products under development that are designed to simultaneously prevent HIV and unintended pregnancy. Since MPTs will be used in the context of sexual relationships, ensuring acceptability and use requires understanding the role of male partners in MPT use decision-making.This paper draws on qualitative data from 39 couples enrolled in the Microbicide Trials Network (MTN) 045 study, conducted in 2019-2020. Partners completed a discrete choice experiment (DCE), first separately and then jointly, to measure preferences for future MPT attributes and then completed a qualitative interview. We also draw on quantitative data from interviewer observation about who dominated the decision-making process during the joint DCE. Content analysis was used to examine (1) how couples made decisions on existing non-MPT HIV and pregnancy prevention products; (2) how couples made decisions on future ideal-MPT product during the DCE; and (3) how these decision-making processes varied by decision-making dominance (10 male, 10 female and 19 equal) and interview type (19 joint and 20 separate).Existing non-MPT product decisions focused on trust between partners and product attributes, while future ideal-MPT product decisions exclusively focused on product attributes. Across existing and future products, preferences for product attributes varied by gender. Male partners were most concerned with limiting side effects impacting sexual pleasure, female partners were most concerned with limiting side effects causing physical symptoms and both were concerned with the return to fertility. Across all dominance and interview types, couples reported making decisions together and female partners were often able to negotiate with male partners for their preferred product or set of product attributes.Research activities in this study provided an opportunity for couples to openly present their product attribute preferences to their partner, learn about their partner's attribute preferences, negotiate for their ideal set of attributes and ultimately choose attributes that benefited the couple without disempowering the female partner. Future research should focus on the utility of couple-based decision-making aids or similar tools for facilitating joint MPT decision-making.

The prevalence of obesity is higher among Black women (56.6%) compared to Hispanic women (50%) and non-Hispanic White women (42%). Notably, interventions to reduce obesity typically result in initial weight loss that is not maintained. This study tested (a) the effectiveness of a 6-month Health-Smart Weight Loss (HSWL) Program for Black women patients with obesity implemented by community health workers (CHWs) within primary care clinics and (b) the comparative effectiveness of two 12-month physician-implemented weight loss maintenance programs-a Patient-Centred Culturally Sensitive Weight Loss Maintenance Program (PCCS-WLM Program) and a Standard Behavioural Weight Loss Maintenance Program (SB-WLM Program). Black women patients (N = 683) with obesity from 20 community primary care clinics participated in the HSWL Program and were then randomized to either maintenance program. The HSWL Program led to significant weight loss (i.e., 2.7 pounds, 1.22 kg, p .01, -1.1%) among the participants. Participants in both the PCCS-WLM Program and the SB-WLM Program maintained their weight loss; however, at month 18, participants in the PCCS-WLM Program had a significantly lower weight than those in the SB-WLM (i.e., 231.9 vs. 239.4 pounds or 105.19 vs. 108.59 kg). This study suggests that (a) the HSWL Program can produce significant weight loss among Black women patients with obesity when implemented in primary care clinics by CHWs, and (b) primary care physicians can be trained to successfully promote weight loss maintenance among their Black women patients.

To understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high-income countries.Using databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age-specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D.In more than 6 million people, 694 454 deaths occurred during a follow-up of 52 million person-years. Trends in all-cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person-years in 50-year-old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80-year-old men; between-country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all-cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes.By reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all-cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia.

AIMS The elevated lifetime risk of cardiovascular disease in women who develop gestational diabetes mellitus (GDM) has been attributed to adverse life-course trajectories of cardiovascular risk factors that arise before pregnancy and continue thereafter. We hypothesized that pregnancy may differentially affect these trajectories in women who develop GDM and those who do not. MATERIALS AND METHODS With population-based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and ≥2 measurements of the following analytes both before and after pregnancy: glycated haemoglobin (HbA1c), glucose, lipids and transaminases. In total, 39 581 women (4373 with GDM) had 3.9 ± 3.4 tests before and 4.6 ± 5.4 tests after pregnancy. RESULTS Both before and after pregnancy, women who developed GDM had higher HbA1c, fasting glucose, low-density lipoprotein (LDL)-cholesterol and triglycerides than their peers, with lower high-density lipoprotein (HDL)-cholesterol (all p

OBJECTIVE To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN A population-based retrospective cohort study (2007-2017). SETTING Ontario, Canada. METHODS Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT Potential twin-specific OGTT thresholds for GDM were identified.

OBJECTIVE We aimed to quantify the risk of future maternal type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) based on the type and number of abnormal 75-g oral glucose tolerance test (OGTT) values and the diagnostic criteria used for the diagnosis of GDM. RESEARCH DESIGN AND METHODS We conducted a population-based retrospective cohort study of all nulliparous women with a live singleton birth who underwent testing for GDM using a 75-g OGTT in Ontario, Canada (2007–2017). We estimated the incidence rate (per 1,000 person-years), overall risk (expressed as adjusted hazard ratio [aHR]), and risk at 5 years after the index pregnancy of future maternal T2DM. Estimates were stratified by the type and number of abnormal OGTT values, as well as by the diagnostic criteria for GDM (Diabetes Canada [DC] vs. International Association of the Diabetes and Pregnancy Study Groups [IADPSG] criteria). RESULTS A total of 55,361 women met the study criteria. The median duration of follow-up was 4.4 (interquartile range 2.8–6.3; maximum 10.3) years. Using women without GDM as reference (incidence rate 2.18 per 1,000 person-years), women with GDM were at an increased risk of future T2DM; this risk was greater when using the DC compared with the IADPSG criteria (incidence rate 18.74 [95% CI 17.58–19.90] vs. 14.07 [95% CI 13.24–14.91] per 1,000 person-years, respectively). The risk of future maternal T2DM increased with the number of abnormal OGTT values and was highest for women with three abnormal values (incidence rate 49.93 per 1,000 person-years; aHR 24.57 [95% CI 21.26–28.39]). The risk of future T2DM was also affected by the type of OGTT abnormality: women with an abnormal fasting value had the greatest risk, whereas women with an abnormal 2-h value had the lowest risk (aHR 14.09 [95% CI 12.46–15.93] vs. 9.22 [95% CI 8.19–10.37], respectively). Similar findings to those described above were observed when the risk of T2DM at a fixed time point of 5 years after the index pregnancy was considered as the outcome of interest. CONCLUSIONS In women with GDM, individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.

Objectives Our aim in this study was to determine the distribution of glycated hemoglobin (A1C) in the Ontario diabetes population and identify subgroups with a high risk of poor glycemic control. Methods In this cross-sectional study, we used real-world clinical data linked with health-care administrative data to identify all people with prevalent diabetes on December 31, 2019. We then identified their most recent A1C result during the year. The distribution of A1C was assessed, and the proportion of those with an A1C of >8.0% was determined, stratified by various sociodemographic and clinical characteristics. Results In the population of 1,009,938 individuals with diabetes, mean ± standard deviation A1C was 7.2±1.4%, with 43.4% of them having an A1C of >7.0% and 19.0% with an A1C of >8.0%. Younger age, remote location of residence, longer diabetes duration and other surrogates for diabetes severity were associated with poor control. Conclusions The mean A1C among people with diabetes in Ontario was 7.2%, but nearly 20% had an A1C of >8%. There were notable disparities in glycemic control that identified several high-risk groups, including younger people, people with longer disease duration and people living in remote areas. Better clinical and policy approaches are needed to improve diabetes care for these populations.

Introduction: The market share of e-scooters in the United States has proliferated in cities: 86 million trips were made on shared e-scooters in 2019, a more than 100% increase compared to 2018. However, the interaction of e-scooters with other road users and infrastructure remains uncertain. Method: This study scrutinized 52 e-scooter and 79 bicycle police-reported crashes in Nashville, Tennessee, from April 2018 to April 2020 from the Tennessee Integrated Traffic Analysis Network (TITAN) database. We used descriptive analysis and a recent prototype version of the Pedestrian and Bicycle Crash Analysis Tool (PBCAT) to classify crashes based on the locations of the crashes relative to roadway segments or intersections, as well as the maneuver of the motor vehicle and e-scooter/bicycle relative to the motor vehicle. Results: Two crash typologies can explain the majority of e-scooter crashes, while bicycle crashes are distributed over several crash typologies. Additionally, 1 in 10 e-scooter- and bicycle-motor vehicle crashes leads to the injury or fatality of the e-scooter rider or bicyclist. Furthermore, we noted statistically significant differences in spatial and temporal distribution, demographics, lighting conditions, and crash distance from home for e-scooter and bicycle crashes. Conclusions: The police crash report provides a comprehensive picture of e-scooter safety complementing existing literature. We found that e-scooter crash characteristics do not fully overlap with features of bicycle crashes. Practical Implications: A generalized engineering, education, and enforcement treatment to reduce and prevent e-scooter and bicycle crashes, injuries, and fatalities might not result in equal outcomes for each mode. More rigorous enforcement could be implemented to deter e-scooters riders under the age of 18 years and e-scooter safety campaigns could target female riders.

Purpose The noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings. Methods and Materials Institutions using the NIBB technique were invited to participate. Data for acute/late toxicity, cosmetic outcome, and tumor recurrence were collected. Toxicity and cosmetic outcome were graded based on the Common Terminology Criteria for Adverse Events version 3.0 and NRG/Radiation Therapy Oncology Group scale, respectively. Treatment variables were analyzed for association with outcomes. Results A total of 252 patients from eight institutions were analyzed. The median age was 69 years. The mean tumor size was 1.1 cm (0.1–4.0 cm). Treatment was delivered 10 fractions (34–36 Gy) in 75% and five fractions (28.5 Gy) in 22%. B.i.d. fractionation was used in 9%. Acute radiation dermatitis was Grade 0–1, 2, and 3 in 77%, 19%, and 4%, respectively. One hundred ninety-one patients with a median followup of 18 months (4–72 months) were evaluable for late outcomes. Late toxicity Grades 2 and 3 were observed in 8.8% and 1%, respectively. Cosmetic outcome was excellent, good, and fair/poor in 62%, 36%, and 2%, respectively. B.i.d. fractionation was associated with higher acute and late toxicity. Second-generation applicators were associated with lower late toxicity and better cosmetic outcome. Actuarial freedom from ipsilateral breast tumor recurrence and true recurrence were 98.3% and 98.3% at 2 years and 90.9% and 95.4% at 5 years, respectively. Conclusions Accelerated partial breast irradiation using NIBB was well tolerated with a low rate of acute and late toxicity across various practice settings. Ipsilateral breast tumor recurrence and cosmetic outcomes were favorable. b.i.d. fractionation was associated with higher toxicity. Longer followup is needed to confirm late endpoints.

PURPOSE OF REVIEW Opioid use disorder (OUD) in pregnancy has more than quadrupled in prevalence over the past two decades and continues to increase steadily every year. With no defined standard of care for the management of pain during the peripartum period, variability in treatment plans potentially leaves room for interrupted patient care, decreased patient satisfaction, and poorer outcomes. The impact of OUD and its management during the peripartum period has become more widely discussed over the past several years and is the focus of this review. RECENT FINDINGS Current recommendations including developing a detailed institutional plan for the management of pain for women with OUD during the intrapartum and postpartum periods. There is tremendous value in exploring partnerships with other specialties, including addiction medicine, and behavioral health and obstetrics in development of policies and procedures. Consistency within institutions is critical to improve patient outcomes. SUMMARY This review will address both pain management recommendations and best clinical practices regarding management of the parturient during the transition periods of the peripartum, intrapartum, and postpartum period. Novel approaches and perspectives from case reports and narrative experience will also be discussed. There are many opportunities in this field for further studies, research, and evidence-based guidelines that promote an established standard of care.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site (https://www.scmr.org) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Aims Pre‐existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease‐2019 (COVID‐19) outcomes. However, data on outcomes of COVID‐19 among people with pre‐existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre‐existing HF with COVID‐19 outcomes. Methods and results A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID‐19 diagnosis among Veterans with and without pre‐existing diagnosis of HF. Cox‐regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID‐19, 6148 had pre‐existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID‐19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61–2.17) and 1.79 (1.66–1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15–1.64) and 1.27 (1.16–1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. Conclusions Patients with COVID‐19 and pre‐existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

Context The optimal 50 g-glucose challenge test (GCT) cutoff for the diagnosis of gestational diabetes mellitus (GDM) in twin pregnancies is unknown. Objective This work aimed to explore the screening accuracy of the 50 g-GCT and its correlation with the risk of large for gestational age (LGA) newborn in twin compared to singleton pregnancies. A population-based retrospective cohort study (2007-2017) was conducted in Ontario, Canada. Participants included patients with a singleton (n = 546 892 [98.4%]) or twin (n = 8832 [1.6%]) birth who underwent screening for GDM using the 50 g-GCT. Methods We compared the screening accuracy, risk of GDM, and risk of LGA between twin and singleton pregnancies using various 50 g-GCT cutoffs. Results For any given 50 g-GCT result, the probability of GDM was higher (P = .0.007), whereas the probability of LGA was considerably lower in the twin compared with the singleton group, even when a twin-specific growth chart was used to diagnose LGA in the twin group (P Conclusion The screening performance of the 50 g-GCT for GDM and its correlation with LGA differ between twin and singleton pregnancies.

Background Venous thromboembolism (VTE) is a serious complication in medically ill inpatients. Enoxaparin or unfractionated heparin (UFH) thromboprophylaxis has been shown to reduce VTE in clinical trials; however, comparative effectiveness and differences in hospital costs are unknown in US hospital practice. Objective This study compared clinical and economic outcomes between enoxaparin and UFH thromboprophylaxis in medically ill inpatients. Methods A retrospective cohort study was conducted using the Premier Healthcare Database between 1 January 2010 and 30 September 2016. Inpatients aged ≥ 18 years with a ≥ 6-day hospital stay for serious medical conditions were included. Two patient groups receiving thromboprophylaxis were identified during hospitalization: one receiving enoxaparin and other receiving UFH. Regression models were constructed to compare VTE events, in-hospital mortality, pulmonary embolism (PE)-related mortality, major bleeding, and total hospital costs during both the index hospitalization and the 90-day readmission period between the two groups. Results A total of 242,474 and 134,384 inpatients received enoxaparin or UFH for thromboprophylaxis, respectively. Compared with UFH prophylaxis, enoxaparin was significantly associated with 15%, 9%, 33%, and 41% reduced odds of VTE, in-hospital mortality, PE-related mortality, and major bleeding, respectively, during index hospitalization, and 10% and 19% reduced odds of VTE and bleeding, respectively, during the readmission period. Mean total hospital costs were significantly lower in patients receiving enoxaparin prophylaxis than in those given UFH. Conclusions Thromboprophylaxis with enoxaparin was associated with significantly reduced in-hospital VTE events, death, and major bleeding and lower hospital costs compared with UFH in hospitalized medically ill patients.

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003–2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24–1.98]) and incident dementia (aHR Depression =1.85 [1.40–2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12–1.29]; aHR Depression =1.19 [1.04–1.37]), incident dementia (aHR Diabetes =1.14 [1.06–1.23]; aHR Depression =1.27 [1.08–1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10–1.26]; aHR Depression =1.24 [1.07–1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23–1.36]; aHR Depression =1.16 [1.05–1.29]). Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

PURPOSE: To test the safety and preliminary efficacy of rapid, non-pharmacologic anesthesia via cooling for intravitreal injections. DESIGN: Single center, randomized, phase 1 dose-ranging safety study (NCT 02872012) SUBJECTS: Adult subjects ≥ 18 years of age with a diagnosis of exudative macular degeneration or diabetic macular edema in both eyes requiring bilateral anti-VEGF therapy were included. METHODS: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye immediately prior to intravitreal treatment (IVT). In 22 subjects undergoing bilateral IVT, one eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at one of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS, 1–10) at 2 timepoints: (1) immediately following IVT, and (2) 4 hours post-IVT. Treated eyes were assessed for ocular safety via biomicroscopic examination performed 24-hours post-IVT. MAIN OUTCOME MEASURES: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately post-IVT and 4-hours post-IVT in eyes receiving cooling anesthesia were compared to eyes receiving SOC. RESULTS: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with lidocaine-based anesthesia. There was no dose-related toxicity with the application of cooling anesthesia. Mild, transient adverse events were recorded in 32% of subjects treated with cooling anesthesia versus 44% of subjects receiving SOC. VAS pain scores immediately following intravitreal injection were 2.3 ± 0.4 for subjects receiving SOC and 2.2 ± 0.6 in subjects receiving −10°C cooling anesthesia (P = 0.8, mean ± SEM). Four hour post-injection pain scores were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined −10°C treatment arms (P = 0.56, mean ± SEM).Total procedure time, including anesthesia and injection, was 124 ± 5 seconds for subjects treated with cooling anesthesia versus 395 ± 40 seconds for the SOC groups (P < 0.0001). CONCLUSIONS: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with −10°C treatment resulting in comparable levels of anesthesia to SOC with a statistically significant reduction in total procedure time.

The blood brain barrier (BBB) is a major obstacle to the delivery of therapeutics to the brain. Focused ultrasound (FUS) in combination with microbubbles can non-invasively open the BBB in a targeted manner. Bolus intravenous injections of microbubbles are standard practice, but dynamic influx and clearance mechanisms prevent delivery of a uniform dose with time. When multiple targets are selected for sonication in a single treatment, uniform serum concentrations of microbubbles are important for consistent BBB opening. Herein, we show that bubble infusions were able to achieve consistent BBB opening at multiple target sites. FUS exposures were conducted with different Definity microbubble concentrations at various acoustic pressures. To quantify the effects of infusion on BBB opening, we calculated the MRI contrast enhancement rate. When infusions were performed at rates of 7.2 µl microbubbles/kg/min or below, we were able to obtain consistent BBB opening without injury at all pressures. However, when infusion rates exceeded 20 µl/kg/min, signs of injury occurred at pressures from 0.39 to 0.56 MPa. When compared to bolus injections, a bubble infusion offers a more controlled and consistent approach to multi-target BBB disruption.

Objectives Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. Materials and methods This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. Results Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. Conclusions Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

Background Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA). Objective To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes. Design Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221). Setting Electronic health care databases from 7 Canadian provinces and the United Kingdom. Patients 208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors. Measurements Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin. Results Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk. Limitations There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites. Conclusion SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect. Primary funding source Canadian Institutes of Health Research.

Background Companion diagnostic (CDx) testing for patients with advanced non‐small cell lung cancer (aNSCLC) identifies patients more likely to benefit from biomarker‐driven treatments. Methods Patients with nonsquamous cell (non‐Sq) aNSCLC from the Flatiron Health database (diagnosed January 1, 2011–May 31, 2018) who had CDx testing were compared with those who had no reported evidence of testing. The association between CDx testing and overall survival was evaluated by unadjusted and adjusted Cox proportional hazards regression models. Logistic regression analysis identified characteristics associated with CDx testing. The revised modified Lung Cancer Prognostic Index and other factors identified a priori were included in the adjusted models. Results A total of 17,555 patients with non‐Sq aNSCLC (CDx, n = 14,732; no CDx, n = 2,823) with mean ± SD age of 67.2 ± 10.0 years were included. Most were insured (91.7%) and white (67.1%). Asian patients and those who were never‐smokers were more likely to undergo CDx testing. Those with CDx testing lived longer than those without (median [95% confidence interval (CI)] survival, 13.04 [12.62–13.40] vs. 6.01 [5.72–6.24] months) and had a decreased mortality risk (adjusted hazard ratio [95% CI], 0.72 [0.69–0.76]). A survival advantage was also seen for patients with CDx testing who received biomarker‐driven first‐line therapy. Conclusion Patients with non‐Sq aNSCLC who had CDx testing had a greater survival benefit than those without, supporting broader use of CDx testing in routine clinical practice to identify patients more likely to benefit from precision medicine. Implications for Practice Companion diagnostic (CDx) testing coupled with biomarker‐driven treatment offers a greater survival benefit for patients with advanced non‐small cell lung cancer (aNSCLC). In this study, patients with nonsquamous aNSCLC from Flatiron Health, a large, real‐world oncology database, with CDx testing had a reduced mortality risk and lived longer than patients without reported evidence of CDx testing; those who received biomarker‐driven therapy as their first line of treatment were likely to survive three times longer than those who did not. These results demonstrate the clinical utility of CDx testing as the first step in treating nonsquamous aNSCLC in real‐world clinical practice., Improved diagnostic and treatment approaches are needed for patients with non‐small cell lung cancer. This article evaluates the testing patterns and outcomes associated with overall companion diagnostic testing in real‐world clinical practice.

Introduction Few studies have examined memory decline among patients with type 2 diabetes using different oral hypoglycemic drugs. Methods Participants with normal cognition (NC) or Alzheimer's disease (AD) dementia using a hypoglycemic medication (2005 to 2019) were identified from the National Alzheimer's Coordinating Center database. Delayed memory was assessed using the Wechsler Memory Scale Revised–Logical Memory test. Associations between oral drug classes and memory over time were examined using mixed‐effects models with inverse probability treatment weights. Results In NC (n = 1192), metformin use was associated with better memory performance over time, whereas in AD (n = 807), dipeptidyl peptidase‐4 (DPP4) inhibitor use was associated with a slower rate of memory decline. Interaction effects suggested greater benefit associated with DPP4 inhibitor use among APOE ε4 carriers. Discussion Associations between different oral hypoglycemic drugs and memory change were not consistent between cognitively normal elderly and those with AD dementia. APOE ε4 genotype modified some relationships.

OBJECTIVE Women who develop gestational diabetes mellitus (GDM) have an elevated lifetime risk of cardiovascular disease, which has been attributed to an adverse cardiovascular risk factor profile that is apparent even within the first year postpartum. Given its presence in the early postpartum, we hypothesized that this adverse cardiovascular risk factor profile may develop over time in the years before pregnancy. RESEARCH DESIGN AND METHODS With population-based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and two or more measurements of the following analytes between 2007 and the start of pregnancy: A1C, fasting glucose, random glucose, lipids, and transaminases. This population consisted of 8,047 women who developed GDM and 93,114 women who did not. RESULTS The two most recent pregravid tests were performed at a median of 0.61 years and 1.86 years before pregnancy, respectively. Women who went on to develop GDM had higher pregravid A1C, fasting glucose, random glucose, LDL cholesterol, triglycerides, and ALT and lower HDL cholesterol than their peers (all P < 0.0001). Notably, in the years before pregnancy, women who went on to develop GDM had higher annual increases than their peers in A1C (1.9-fold higher) (difference 0.0089%/year [95% CI 0.0043–0.0135]) and random glucose (4.3-fold), greater annual decrease in HDL cholesterol (5.5-fold), and lesser annual decline in LDL cholesterol (0.4-fold) (all P ≤ 0.0002). During this time, fasting glucose and triglycerides increased in women who developed GDM but decreased in their peers (both P < 0.0001). CONCLUSIONS The adverse cardiovascular risk factor profile of women with GDM evolves over time in the years before pregnancy.

OBJECTIVE Reports of amputations associated with sodium–glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results. RESULTS The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71–1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule. CONCLUSIONS In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.

BACKGROUND AND AIMS: Calcific aortic valve disease is highly prevalent in patients with significant smoking history and is a marker of atherosclerosis. The aim of this study was to define the prognostic value of aortic valve calcification (AVC) derived from low dose, lung cancer screening computed tomography (LCSCT) for all-cause mortality in this higher risk population. METHODS: This is a single site, retrospective analysis of 1529 moderate-to-high atherosclerotic cardiovascular risk U.S. veterans (65 years [IQI: 61, 68] years; 96% male), who underwent clinically indicated LCSCT. CTs were scored for aortic valve calcification (AVC) and coronary artery calcification (CAC). The primary endpoint was all-cause mortality and secondary endpoints were nonfatal myocardial infarction (MI) and nonfatal cerebrovascular accident (CVA). RESULTS: Over 4-year follow-up, 227 patients (15%) died, 112 patients (7%) had nonfatal MI, and 52 patients (3%) had nonfatal CVA. AVC was predictive of all-cause mortality (HR per 100: 1.041 [1.030–1.052], p < 0.001), and this association remained significant after multivariate adjustment for traditional atherosclerotic risk factors, including CAC (1.021 [1.007–1.036], p = 0.003). After excluding patients with severe aortic stenosis (AS) or severe AVC (≥1274 AU in women and ≥2065 AU in men), in a subset of 765 patients who had echocardiograms, this association remained significant after multivariate analysis (HR per 100: 1.052 [1.010–1.095], p = 0.014). Despite controlling for CAC in the models, AVC was still associated with MI (HR per 100: 1.021 [1.004–1.039], p = 0.017) and with CVA (HR per 100: 1.027 [1.002–1.051], p = 0.032). CONCLUSIONS: Scoring AVC derived from LCSCT is predictive of mortality, nonfatal MI, and nonfatal CVA in patients at known risk for cardiovascular disease, independent of coronary calcification or severe aortic valve stenosis.

OBJECTIVE To examine whether neighborhood socioeconomic status (SES) is a predictor of non-drug-related health care costs among Canadian adults with diabetes and, if so, whether SES disparities in costs are reduced after age 65 years, when universal drug coverage commences as an insurable benefit. RESEARCH DESIGN AND METHODS Administrative health databases were used to examine publicly funded health care expenditures among 698,113 younger (20–64 years) and older (≥65 years) adults with diabetes in Ontario from April 2004 to March 2014. Generalized linear models were constructed to examine relative and absolute differences in health care costs (total and non-drug-related costs) across neighborhood SES quintiles, by age, with adjustment for differences in age, sex, diabetes duration, and comorbidity. RESULTS Unadjusted costs per person-year in the lowest SES quintile (Q1) versus the highest (Q5) were 39% higher among younger adults ($5,954 vs. $4,270 [Canadian dollars]) but only 9% higher among older adults ($10,917 vs. $9,993). Adjusted non-drug costs (primarily for hospitalizations and physician visits) were $1,569 per person-year higher among younger adults in Q1 vs. Q5 (modeled relative cost difference: 35.7% higher) and $139.3 million per year among all individuals in Q1. Scenarios in which these excess costs per person-year were decreased by ≥10% or matched the relative difference among seniors suggested a potential for savings in the range of $26.0–$128.2 million per year among all lower-SES adults under age 65 years (Q1–Q4). CONCLUSIONS SES is a predictor of diabetes-related health care costs in our setting, more so among adults under age 65 years, a group that lacks universal drug coverage under Ontario’s health care system. Non-drug-related health care costs were more than one-third higher in younger, lower-SES adults, translating to >$1 billion more in health care expenditures over 10 years.

Traumatic popliteal artery injury is associated with an increased propensity for limb loss, morbidity, and mortality above an already elevated baseline risk to life and limb. Previous studies of outcomes in this patient group have been limited by selection bias. This study analyzed outcomes after blunt popliteal artery injury using propensity matching to reduce confounding variables associated with multiple mechanisms of traumatic vascular injury and to identify factors associated with amputation.A retrospective review was conducted of prospectively collected data from the National Trauma Data Bank. Patients were identified using International Classification of Diseases, Ninth Revision codes related to patterns of blunt injury associated with popliteal arterial injury or intervention. Using Trauma Quality Improvement Program variables as a reference, specific characteristics were collected. Variables found significant on univariate analysis were used to generate propensity-matched amputation and nonamputation cohorts. Multivariate logistic regression was used to assess for risk factors associated with amputation and inpatient mortality.In total, 3029 patients with blunt popliteal artery injury were identified; 628 (20.7%) underwent amputation. Patients who underwent amputation presented with more frequent hypotension (systolic blood pressure of 0-99 mm Hg, 22.7% vs 12.8%; P .001) and tachycardia (heart rate120 beats/min, 28.5% vs 14.5%; P .001). Limb loss was also associated with concurrent popliteal vein injury (18.3% vs 8.7%; P .001) and tibial nerve injury (5.3% vs 1.3%; P .001) as well as with elevated Injury Severity Score (median, 13 vs 9; P .001) and lower extremity Abbreviated Injury Scale score (3 vs 2; P .001). Subsequently, 794 patients were divided into equal number propensity-matched amputation and nonamputation cohorts. Regression analysis revealed that patients with diabetes mellitus (odds ratio [OR], 1.763; P = .049), popliteal vein injury (OR, 1.657; P = .012), or tibial nerve injury (OR, 3.537; P = .007) were more likely to undergo amputation. Further regression analysis with patients matched for Injury Severity Score revealed that age ≥86 years (OR, 38.092; P = .009), patellar fracture (OR, 3.445; P = .036), and elevated Abbreviated Injury Scale score (OR, 1.101; P .001) were associated with higher risk of inpatient death.Trauma patients who sustain blunt popliteal artery injury are at an increased risk of amputation. Propensity-matched analysis revealed that concurrent popliteal vein and tibial nerve injury but not severity of tissue injury predicted limb loss.

Enoxaparin and unfractionated heparin (UFH) are guideline-recommended anticoagulants for patients with acute coronary syndrome (ACS), including unstable angina (UA) and myocardial infarction with (STEMI) or without ST-segment elevation (NSTEMI). Prior efficacy and safety evidence are mainly from clinical trials. Economic data are insufficient. This study examined the differences in utilization, effectiveness, safety, and costs in treating ACS between enoxaparin and UFH monotherapy using real-world data. Using data from 859 US hospitals, inpatients ≥ 18 years of age with a diagnosis of an initial episode of ACS between 2010 and 2016 were identified. Outcomes included 30-day risk of non-fatal myocardial infarction (MI), recurrent angina, in-hospital mortality, composite ischemic complication (having MI/recurrent angina/death), major bleeding, and costs. Multivariable regression was used to compare outcomes between enoxaparin and UFH monotherapy. Among 1,048,053 eligible patients (UA: 219,259; NSTEMI: 582,134; STEMI: 246,660), the prevalence of enoxaparin monotherapy was 12.0%, 13.9%, and 5.1%, and the prevalence of UFH monotherapy was 45.1%, 43.1% and 59.8%, for UA, NSTEMI, and STEMI patients, respectively. Enoxaparin was associated with a lower risk of ischemic complications and death among NSTEMI, but not in UA or STEMI patients, and with a lower risk of major bleeding in all patients. Cost savings per patient during index admission and 30-day follow-up for enoxaparin over UFH was $2972 for UA, $2475 for NSTEMI, and $3050 for STEMI. Enoxaparin was associated with a lower risk of ischemic complications (including death), lower costs, and better safety than UFH among NSTEMI patients. Improving upstream selection of anticoagulants in appropriate populations may help optimize clinical outcomes and costs.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

OBJECTIVES Surgical resection is one treatment modality for chronic pulmonary aspergillosis (CPA), and sometimes a preoperative presumption of lung cancer turns out to be CPA. We have audited our surgical experience with regard to risk factors for relapse, and the value of postoperative monitoring of Aspergillus-immunogolubulin G (IgG) titres. METHODS All patients with CPA surgically treated at National Aspergillosis Centre (NAC), Manchester, UK (2007–2018), were retrospectively evaluated. Surgical procedures, underlying disorders, Aspergillus-IgG titres (ImmunoCap) and antifungal therapy were evaluated for symptom control, operative complications, CPA relapse and mortality. RESULTS A total of 61 patients with CPA (28 males, 33 females) were operated on primarily for antifungal therapy failure (51%, n = 31) and presumed lung malignancies (38%, n = 23). Procedures included lobectomy (64%, n = 39), wedge resection (28%, n = 17), segmentectomy (n = 3), pneumonectomy (n = 3) and decortication (n = 2). Overall, 25 (41%) patients relapsed, 26 months (standard deviation: 24.8 months) after surgery. Antifungal therapy before surgery (P = 0.002) or both before and after surgery (P = 0.005) were protective for relapse. The relapse rate within 3 years after surgery (33%, n = 20) was higher than the 3–10 years after surgery (8%, n = 5). At the end of follow-up, the median Aspergillus-IgG titre was lower than at relapse in 12 patients (67 vs 126 mg/l) (P = 0.016). CONCLUSIONS Surgery in these selected patients with CPA resulted in favourable outcomes. Relapse is common after surgical treatment of CPA but can be minimized with antifungal therapy, emphasizing the importance of an accurate diagnosis prior to surgery.

The purpose of this study is to characterize the epidemiology, injury patterns, outcomes and trends of non-accidental trauma (NAT) in the United States using a large national database.Children15 years presenting after NAT were identified in the 2007-2014 National Trauma Databank research datasets. Clinical and outcome data were analyzed using descriptive statistics, chi-square and logistic regression.Of 678,503 children admitted for traumatic injuries, 3% (19,149) were victims of NAT. The majority (95%) were under 5 years and 71% under 1 year old. The majority (59%) were male. The median injury severity score (ISS) was 10 (IQR:5-19). African Americans were disproportionally affected (27% vs 17% of all traumas), and the majority had public or no insurance (85%). Incidence was highest in the midwest and lowest in the northeast regions of the country, although trends varied over time. NAT resulted in 43% of trauma deaths in children1 year and 31% of trauma deaths in children5. Traumatic brain injury (TBI) was the most commonly encountered diagnosis (50%). Polytrauma was common, and certain injury patterns were identified. Urgent operation was required in 6%, 43% were admitted to intensive care, and 9% died. Mortality was independently associated with TBI, thoracic injury, hollow viscus injury and older age.Non-accidental trauma is a leading cause of trauma mortality in young children. Multiple injuries are common, requiring comprehensive evaluation and early surgical involvement. The data presented in this study could serve as a guide to target injury prevention efforts.III STUDY TYPE: Prognostic and Epidemiological.

Aims To evaluate the impact of the integration of onsite diabetes education teams in primary care on processes of care indicators according to practice guidelines. Methods Teams of nurse and dietitian educators delivered individualized self-management education counseling in 11 Ontario primary care sites. Of the 771 adult patients with HbA1c ≥7% who were recruited in a prospective cohort study, 487 patients attended appointments with the education teams, while the remaining 284 patients did not (usual care group). Baseline demographic, clinical information, and patient care processes (diabetes medical visit, HbA1c test, lipid profile, estimated glomerular filtration rate, and albumin-to-creatinine ratio, measuring blood pressure, performing foot exams, provision of flu vaccine, and referral for dilated retinal exam) were collected from patient charts one year before (pre period) and after (post period) the integration began. A multi-level random effects model was used to analyze the effect of group and period on whether the process indicators were met based on practice guidelines. Results Compared to the usual care group, patients seen by the education teams had significant improvements on indicators for semi-annual medical visit and annual foot exam. No significant improvements were found for other process of care indicators. Conclusions Onsite education teams in primary care settings can potentially improve diabetes management as shown in two process of care indicators: medical visits and foot exams. The results support the benefits of having education teams in primary care settings to increase adherence to practice guidelines.

OBJECTIVES To evaluate the rate of, and reasons for, conversion of closed treatment of humeral shaft fractures using a fracture brace, to surgical intervention. DESIGN Multicenter, retrospective analysis. SETTING Nine Level 1 trauma centers across the United States. PATIENTS A total of 1182 patients with a closed humeral shaft fracture initially managed nonoperatively with a functional brace from 2005 to 2015 were reviewed retrospectively from 9 institutions. INTERVENTION Functional brace. MAIN OUTCOME MEASUREMENTS Conversion to surgery. RESULTS A total of 344 fractures (29%) ultimately underwent surgical intervention. Reasons for conversion included nonunion (60%), malalignment beyond acceptable parameters (24%), inability to tolerate functional bracing (12%), and persistent signs of radial nerve palsy requiring exploration (3.7%). Univariate comparisons showed that females and whites were significantly (P < 0.05) more likely to be converted to surgery. The multivariate logistic regression identified females as being 1.7 times more likely and alcoholics to be 1.4 times more likely to be converted to surgery (P < 0.05). Proximal shaft as well as comminuted, segmental, and butterfly fractures were also linked to a higher rate of conversion. CONCLUSIONS This large multicenter study identified a 29% surgical conversion rate, with nonunion as the most common reason for surgical intervention after the failure of functional brace. These results are markedly different than previously reported. These results may be helpful in the future when counseling patients on the choice between functional bracing and surgical intervention in managing humeral shaft fractures. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. Methods Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM−/CVD+); those with GDM but no CVD (GDM+/CVD−); and those with neither GDM nor CVD (GDM−/CVD−). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up. Results On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM−/CVD− to GDM+/CVD− to GDM−/CVD+ to GDM+/CVD+ (all ppp Conclusions Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population.

BACKGROUND: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. OBJECTIVE: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. METHODS: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018–2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. RESULTS: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0–2.6), history of coronary revascularization (OR = 4.0, CI, 3.2–5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7–3.4). Blacks (OR = 0.7, CI, 0.6–0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48–0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6–0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18–1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. CONCLUSION: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.

As observational studies support the association between periodontal disease (PD) and cardiovascular diseases (CVDs), we examined this relationship using the National Health and Nutrition Examination Survey 2013 to 2014 data. This cross-sectional study involved 2,830 adult participants, aged ≥30 years who underwent a home interview, followed by a standardized assessment at a mobile examination center from 2013 to 2014. PD was defined using the new classification scheme issued by American Academy of Periodontology Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions in 2017, and CVD was defined as the composite of coronary artery disease and stroke. The gathered data were subjected to weighted statistical analysis to examine the relation between CVD prevalence and PD. The sample (mean age 51.5 ± 13.6 years) comprised 50.1% men and 69.5% White participants. Stage I (mild/subclinical), II (moderate), and III to IV (severe) PD was noted in 16.7% (95% confidence interval [CI] 12.7 to 21.7), 57.4% (95% CI 53.9 to 60.9), and 25.9% (95% CI 21.4 to 30.8) of the participants, respectively. Patients with stage III and IV PD were more likely to have CVD than those with stage I (adjusted odds ratio 3.59, 95% CI 1.12 to 11.54, p = 0.03). Similarly, participants who reported fair/poor gum health were more likely to have CVD than those who reported excellent/very good gum health (adjusted odds ratio 2.17, 95% CI 0.98 to 4.79, p = 0.055). In conclusion, the data from the National Health and Nutrition Examination Survey 2013 to 2014 demonstrated that PD severity is associated with CVD risk. However, the information gathered by trained professionals during periodontal examinations is a more reliable predictor of PD-CVD associations compared with self-reported measures of oral health.

Women with a history of pre-eclampsia have an elevated lifetime risk of cardiovascular disease that may be partly attributed to an adverse cardiovascular risk factor profile, the etiology of which is unclear. Hypothesising that this adverse risk profile may begin to arise over time in the years before pregnancy, we sought to evaluate the pregravid changes over time in cardiovascular risk factors in women who go on to develop pre-eclampsia and those who do not.Retrospective cohort study using population-based administrative databases.Ontario, Canada.All nulliparous women who had singleton pregnancies between January 2011 and December 2018.All results for the following analytes between January 2008 and the start of pregnancy were identified: A1c, glucose, lipids, and transaminases. Mean values were compared between those with and without preeclampsia. The annual change for each analyte in the years before pregnancy was estimated using generalized estimating equations.Preeclampsia.The 156 278 women (of whom 3827 developed preeclampsia) had mean 4.0 ± 3.3 pregravid tests overall. The two most recent pregravid tests were performed at median 0.6 and 1.9 years before pregnancy, respectively. Women who developed pre-eclampsia had higher pregravid A1c, fasting glucose, random glucose, LDL-cholesterol, triglycerides, and ALT, and lower HDL-cholesterol, than their peers (all P0.0001). In the years before pregnancy, women who went on to develop pre-eclampsia had higher annual increases than their peers in triglycerides (13.8-fold higher; P = 0.0004) and random glucose (1.55-fold higher; P = 0.001), coupled with a greater annual decrease in HDL-cholesterol (9.7-fold higher; P = 0.002). During this time, fasting glucose increased in women who developed pre-eclampsia but decreased in their peers (P = 0.01).In women who develop pre-eclampsia, an adverse cardiovascular risk factor profile evolves over time in the years before pregnancy.In women who develop pre-eclampsia, an adverse CV risk factor profile evolves in the years before pregnancy.

Importance: COVID-19 altered lifestyles and disrupted routine health care. Whether blood pressure (BP) control worsened during COVID-19 is unknown. Objective: To understand whether home BP control worsened during COVID-19 across the United States (US). Design, Setting, and Participants: A population-based analysis of home BP data from 72,706 participants enrolled in a digital health hypertension control program. Data was compared before (January 2019 to March 2020) and during (April 2020 to August 2020) COVID-19. Main Outcomes and Measures: Monthly mean home BP readings, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were quantified before and during the pandemic. Multivariable adjustments were made for age, sex, race, region, and months enrolled. Home BP readings were also classified based on monthly averages and highest home BP readings into risk groups: Stage 2 HTN: BP>=135 or DBP>=85; Uncontrolled HTN: SBP>=145 or DBP>= 95; or Severely uncontrolled HTN: SBP>=160 or DBP>=100). Results: Overall, 72,706 participants were enrolled in a digital health hypertension program between 1/1/2019 and 8/31/2020. Compared with participants pre-COVID-19 (n= 33,440), those during COVID-19 (n=39,266) were of similar age (mean 53.0 ± 10.7 years vs 53.3±10.8 years); sex (46% vs 50.6% female) and race (29.1% vs 34.2% non-white). Relative to pre-Covid (Apr-Aug 2019) the mean monthly number of home BP readings rose during COVID-19 (Apr-Aug, 2020), from 7.3 to 9.3 per month (p < 0.001). During COVID-19, participants had higher monthly adjusted mean SBP (131.6 mmHg vs. 127.5 mmHg, p

Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, and fire-fighting foams which have become environmental pollutants of concern due to their persistence, ubiquity, and associations with adverse human health outcomes, including in pregnant persons and their offspring. Multiple PFAS are associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver are not fully described. Here we performed transcriptomic analyses in the mouse to investigate the molecular mechanisms of hepatic toxicity in the dam and its fetus after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, known as GenX). Pregnant CD-1 mice were exposed via oral gavage from embryonic day (E) 1.5-17.5 to PFOA (0, 1, or 5 mg/kg-d) or GenX (0, 2, or 10 mg/kg-d). Maternal and fetal liver RNA was isolated (N = 5 per dose/group) and the transcriptome analyzed by Affymetrix Array. Differentially expressed genes (DEG) and differentially enriched pathways (DEP) were obtained. DEG patterns were similar in maternal liver for 5 mg/kg PFOA, 2 mg/kg GenX, and 10 mg/kg GenX (R

ImportanceAccruing evidence suggests that gestational hypertensive disorders (GHTD) and gestational diabetes (GD) are each associated with an increased risk of cardiovascular disease (CVD). However, the extent to which the co-occurrence of GHTD and GD is associated with the risk of CVD remains largely unknown.ObjectiveTo estimate the individual and joint associations of GHTD and GD with incident CVD.Design, Setting, and ParticipantsThis population-based cohort study used the Ministry of Health and Long-Term Care of Ontario (Canada) health care administrative databases. All women in Ontario with a GHTD and/or GD diagnosis, and a live-birth singleton delivery between July 1, 2007, and March 31, 2018, were considered for inclusion. Women with pregravid diabetes, hypertension, or cardiovascular disease were excluded. Statistical analysis was performed from November 2021 to September 2022.ExposuresGD and/or GHTD, defined using diagnosis coding.Main Outcomes and MeasuresIndividual and joint associations of GHTD and GD with incident CVD (including a composite of myocardial infarction, acute coronary syndrome, stroke, coronary artery bypass grafting, percutaneous coronary intervention, or carotid endarterectomy), estimated using Cox regression models, adjusting for relevant cardiometabolic risk factors. The follow-up extended from the index pregnancy until March 31, 2020.ResultsAmong 886 295 eligible women (mean [SD] age, 30 [5.6] years; 43 861 [4.9%] with isolated GHTD, 54 061 [6.1%] with isolated GD, and 4975 [0.6%] with GHTD and GD), there were 1999 CVD events over 12 years of follow-up. In the early postpartum phase (first 5 years post partum), there was no association of co-occurrence of GTHD and GD (adjusted hazard ratio [aHR], 1.42, 95% CI, 0.78-2.58) or GD alone (aHR, 0.80; 95% CI, 0.60-1.06) with CVD; there was an association between isolated GTHD and incident CVD compared with no GTHD and no GD (aHR, 1.90; 95% CI, 1.51-2.35). In the late postpartum period (after the initial 5 years post partum), compared with no GD and no GHTD, isolated GHTD (aHR, 1.41, 95% CI, 1.12-1.76) and co-occurrence of GHTD and GD (aHR, 2.43, 95% CI, 1.60-3.67) were each associated with a higher risk of incident CVD. There was no association between isolated GD and incident CVD.Conclusions and RelevanceIn this cohort study, GHTD was associated with a high risk of CVD post partum, and the co-occurrence of GD and GHTD was associated with a much greater postpartum CVD risk. These findings suggest that CVD preventive care is particularly needed in the aftermath of combined GD and GHTD.

Aim . - We assessed the risk of all-cause hospitalization and all-cause death associated with the use of Sodium Glucose Cotransporter-2 inhibitors (SGLT2i). Methods . - Population-based propensity scores-matched cohort study of new users of metformin who subsequently initiated SGLT2i compared to those who initiated dipeptidyl peptidase-4 inhibitors (DPP4i) (primary comparison), sulfonylureas, thiazolidinediones, GLP1-Receptors agonists, and insulin, respectively. Alberta (Canada) health administrative data and United Kingdom Clinical Practice Research Datalink (CPRD) data were used to assess the study outcomes. Conditional Cox regressions were performed to assess the risk of each outcome, separately for each dataset and then results were combined using random-effects meta-analysis. Results . - For SGLT2i versus DPP4i, 7531 and 1647 SGLT2i-DPP4i matched pairs were analyzed in Alberta and CPRD data respectively. The mean age of patients was 56 and 57 years, and 39 % and 43% were females, respectively in Alberta and CPRD cohorts. Compared with DPP-4-i, SGLT2i use was associated with a significant lower risk of all-cause hospitalization (combined hazard ratio (HR): 0.84, 95% confidence interval (95%CI): 0.75-0.95), and all-cause death (0.56, 0.38-0.83). SGLT2i use was also associated with a significant lower risk of all-cause hospitalization and all-cause death when compared to sulfonylureas (HRs: 0.80, 95%CI: 0.71-0.90 and 0.56, 95%CI: 0.38-0.82, respectively) and insulin (HRs: 0.55, 95%CI: 0.41-0.74, and 0.33, 95%CI: 0.24-0.46, respectively). Conclusions . - SGLT2i initiation was associated with a decreased risk of all-cause hospitalization and all-cause death when compared to DPP4i, sulfonylureas, and insulin.

Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud

BACKGROUND: Population-based planning tools are important for informing diabetes-prevention efforts in First Nations communities. We used the Diabetes Population Risk Tool (DPoRT) to predict 10-year diabetes risk and describe the factors that contribute to diabetes risk in First Nations adults living in Ontario First Nations communities. METHODS: We examined population data from adult (≥ 20 yr) respondents to the First Nations Regional Health Survey (RHS) phase 3, a representative cohort of First Nations people living in Ontario First Nations communities. We applied the DPoRT to risk factor information in the survey to predict the distribution of 10-year type 2 diabetes incidence and number of new diabetes cases from 2015/16 to 2025/26. RESULTS: There were 993 respondents to the RHS phase 3 adult survey, of whom 936 (708 without diabetes and 228 with a diagnosis of type 2 diabetes) were eligible for inclusion. The DPoRT predicted a type 2 diabetes risk of 9.6% (confidence interval [CI] 8.3–10.8) between 2015/16 and 2025/26, corresponding to 3501 (95% CI 2653–4348) new diabetes cases. Diabetes cases were predicted to occur disproportionately among those experiencing food insecurity, low income, overweight, obesity and physical inactivity. Reduced diabetes risk was predicted among those who reported connections to Indigenous culture, as measured by eating traditional vegetative foods a few times or often in the previous 12 months. INTERPRETATION: Socioeconomic conditions and known risk factors for type 2 diabetes are important determinants of diabetes risk in First Nations communities. Culturally appropriate policies, programming and services that address socioeconomic disadvantage and other diabetes risk factors in First Nations communities likely have an important role for diabetes prevention in First Nations adults.

Background In Canada, increasing numbers of women, especially First Nations women, are affected by diabetes during pregnancy, which is a major risk factor for adverse maternal and neonatal outcomes. The aim of this study was to examine temporal trends in pregnancy outcomes and use of health care services in a population-based cohort of First Nations women compared to other women in Ontario according to diabetes status during pregnancy. Methods Using health administrative databases, we created annual cohorts of pregnant women from 2002/03 to 2014/15 and identified those with preexisting diabetes and gestational diabetes. We used the Indian Register to identify First Nations women. We estimated rates of adverse maternal and infant outcomes, and measures of use of health care services in each population. Results There were 1 671 337 deliveries among 1 065 950 women during the study period; of these deliveries, 31 417 (1.9%) were in First Nations women, and 1 639 920 (98.1%) were in other women. First Nations women had a higher prevalence of preexisting diabetes and gestational diabetes than other women in Ontario. First Nations women with preexisting diabetes had higher rates of preeclampsia (3.2%-5.6%), labour induction (33.4%-42.9%) and cesarean delivery (47.8%-53.7%) than other women in Ontario, as did First Nations women with gestational diabetes (3.2%-4.7%, 38.5%-46.9% and 41.4%-43.4%, respectively). The rate of preterm birth was similar between First Nations women and other women in Ontario. Although First Nations women had a higher rate of babies who were large for gestational age than other women, regardless of diabetes status, obstructed labour rates were similar for the 2 cohorts. Almost all First Nations women, regardless of diabetes status, were seen by a primary care provider during their pregnancy, but rates of use of specialty care were lower for First Nations women than for other women. Fifteen percent of all pregnant women with preexisting diabetes visited an ophthalmologist during their pregnancy. Interpretation Our results confirm disparities in maternal and neonatal outcomes between First Nations women and other women in Ontario. Access to primary care for pregnant women seemed adequate, but access to specialized care, especially for women with preexisting diabetes, needs to improve.

Purpose Clinical prediction of disease severity is important as one considers nonoperative management of simple appendicitis. This study assesses the accuracy of surgeons' prediction of appendicitis severity. Methods From February to August 2016, pediatric surgeons at a single institution were asked to predict whether patients had simple or complex appendicitis preoperatively based on clinical data, imaging, and general assessment. Receiver operating characteristic curves were generated to determine area under the curve (AUC) and optimal cutoff points of clinical findings for diagnosing simple appendicitis. Outcomes included sensitivity and specificity of variables to identify simple appendicitis. Predictions were compared to operative findings using χ2. A p-value Results Of 125 cases (median age 9 years [IQR 7–13], 58% male), simple appendicitis was predicted in 77 (62%) and complex appendicitis in 48 (38%). Predictions were accurate in 59 (77%) simple cases and 45 (94%) complex cases. Although surgeon prediction was more accurate than individual imaging or clinical findings and was highly sensitive (95%) for diagnosing simple appendicitis, specificity was only 71%. Lower WBC ( Conclusion While surgeon prediction of simple appendicitis is more accurate than ultrasound or clinical data alone, diagnostic accuracy is still limited. Type of study Prospective survey. Level of evidence II