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There is wide variation in mortality among patients hospitalized with COVID-19. Whether this is related to patient or hospital factors is unknown.To compare the risk of mortality for patients hospitalized with COVID-19 and to determine whether the majority of that variation was explained by differences in patient characteristics across sites.An international multicenter cohort study of hospitalized adults with laboratory-confirmed COVID-19 enrolled from 10 hospitals in Ontario, Canada and 8 hospitals in Copenhagen, Denmark between January 1, 2020 and November 11, 2020.Inpatient mortality. We used a multivariable multilevel regression model to compare the in-hospital mortality risk across hospitals and quantify the variation attributable to patient-level factors.There were 1364 adults hospitalized with COVID-19 in Ontario (n = 1149) and in Denmark (n = 215). In Ontario, the absolute risk of in-hospital mortality ranged from 12.0% to 39.8% across hospitals. Ninety-eight percent of the variation in mortality in Ontario was explained by differences in the characteristics of the patients. In Denmark, the absolute risk of inpatients ranged from 13.8% to 20.6%. One hundred percent of the variation in mortality in Denmark was explained by differences in the characteristics of the inpatients.There was wide variation in inpatient COVID-19 mortality across hospitals, which was largely explained by patient-level factors, such as age and severity of presenting illness. However, hospital-level factors that could have affected care, including resource availability and capacity, were not taken into account. These findings highlight potential limitations in comparing crude mortality rates across hospitals for the purposes of reporting on the quality of care.

OBJECTIVES Inappropriate prescribing of medications is common in health care, and is an important safety concern, especially for older adults, who have a high burden of comorbidity and are at greater risk for medication-related adverse events. This study aims to estimate the extent and cost of potentially inappropriate prescribing of medications to older adults in the United States. DESIGN A cross-sectional study. SETTING Medicare Part D Prescription Drug Program data set (2014-2018). PARTICIPANTS Older adults who were enrolled in Medicare Part D Prescription Drug Program between 2014 and 2018. MEASUREMENTS Potentially inappropriate medications were identified using the 2019 American Geriatrics Society Beers Criteria®. RESULTS In 2018, 7.3 billion doses of potentially inappropriate medications were dispensed. The most common medications by number of doses dispensed were proton pump inhibitors, benzodiazepines, and tricyclic antidepressants, and the top five unique medications by reported spending were dexlansoprazole, esomeprazole, omeprazole, dronedarone, and conjugated estrogens. From 2014 to 2018, 43 billion doses of potentially inappropriate medications were dispensed, with a reported spending of $25.2 billion. CONCLUSION Potentially inappropriate medication use among older adults is both common and costly. Careful attention to potentially inappropriate medication use and deprescribing when clinically appropriate could reduce costs and potentially improve outcomes among older adults.

PURPOSE: To determine how commonly pre-approval clinical trials could potentially be replicated using real-world data from insurance claims databases. METHODS: We conducted a cross-sectional study of medications approved by the FDA in 2011. For each medication, we reviewed the drug's label and the details of the pivotal clinical trials supporting its approval. We assessed whether each clinical trial could be replicated using an insurance claims databases by determining whether the following pivotal trial features could be reliably captured in claims data: study outcome, inclusion criteria, exclusion criteria, and the presence of an appropriate active comparator. RESULTS: In 2011, 28 new medications were approved. The most common disease areas were oncology (N = 8, 29%), infectious disease (N = 5, 18%), and neurology (N = 4, 14%). The primary outcome of pre-approval clinical trials was identifiable in claims databases for six (21%) of the medications. Two (ticagrelor and linagliptin) had at least 80% of inclusion and exclusion criteria that could be identified in claims databases and had an available active comparator. The non-identifiable primary outcomes were related to patient-reported symptoms (N = 9, 32%), imaging findings (N = 5, 18%), laboratory values (N = 5, 18%), or other measurements (eg, blood pressure) not typically available in insurance claims databases (N = 4, 14%). CONCLUSIONS: Among drugs FDA-approved in 2011, two (7%) had a pre-approval trial that could be replicated using insurance claims databases. In such qualifying trials, replication using claims databases could be useful in assessing whether they provide concordant results.

Maternal schizophrenia is associated with adverse birth outcomes, but the reasons for this remain unclear. In a population-based cohort of infants born to women with schizophrenia, we determined the occurrence of key perinatal outcomes and explored whether factors identifiable in our datasets explained any elevated risk. Using population-level health administrative data linked to clinical birth-registry data in Ontario, Canada (2006–2011), we examined the relative risk (RR) of preterm birth (

Objective: To examine the association between maternal country of birth and the risk of preeclampsia+preterm birth (PTB). Study Design: We completed a population-based study in the entire province of Ontario, where there is universal access to obstetrical care. We included 881 700 singleton livebirths among Canadian-born mothers and 305 547 births among immigrant mothers. Adjusted risk ratios (aRRs) were adjusted for maternal age, parity and income quintile. Results: Compared with a rate of preeclampsia+PTB of 4.0 per 1000 among Canadian-born mothers, the aRR of preeclampsia+PTB at 24 to 36 weeks was significantly higher for immigrant women from Nigeria (1.79, 95% confidence interval (CI) 1.12 to 2.84), the Philippines (1.54, 95% CI 1.30 to 1.86), Colombia (1.68, 95% CI 1.04 to 2.73), Jamaica (2.06, 95% CI 1.66 to 2.57) and Ghana (2.12, 95% CI 1.40 to 3.21). The aRRs generally followed a similar pattern for secondary outcomes. Specifically, women from Ghana were at highest risk of preeclampsia+very PTB (4.55, 95% CI 2.57 to 8.06), and women from Jamaica at the highest risk of preeclampsia+indicated PTB (1.89, 95% CI 1.43 to 2.50). Conclusion: The risk of preeclampsia+PTB is highest among women from a select number of countries. This information can enhance initiatives aimed at reducing the risk of PTB related to preeclampsia.

Objective To assess the influence of neighbourhood-level adult premature mortality on a woman's risk of preterm delivery (PTD). Methods We included 286 872 singleton live birth deliveries in Toronto, Ontario, between 2002 and 2011. The study exposure was neighbourhood premature mortality rate, expressed in quintiles (Q), among adults aged 20 to 49 years living within each of Toronto's 140 neighbourhoods. The primary study outcome was PTD at 24 to 36 weeks' gestation. Logistic regression analysis generated unadjusted ORs, adjusted ORs, and 95% CIs, controlling for maternal age, parity, marital status, material deprivation index Q, maternal and paternal birthplace, and infant sex. Results For all 140 neighbourhoods, the mean rate of premature deaths was 0.66 per 100 females and 1.17 per 100 males aged 20 to 49 years. The rate of PTD increased linearly in relation to the neighbourhood rate of premature mortality among adult females, from 5.3 per 100 in Q1 with the lowest rate of premature mortality to 6.3 per 100 in Q5 (OR 1.22; 95% CI 1.13 to 1.31). The adjusted ORs were attenuated but remained significant (1.13; 95% CI 1.05 to 1.22). A similar pattern was demonstrated for the relation between neighbourhood premature mortality among adult males and PTD. Conclusion Women residing in neighbourhoods with high rates of premature adult mortality are at elevated risk of PTD, even after adjusting for measured socioeconomic factors that include marital status and material deprivation.

Delayed gastric emptying is present in patients with functional dyspepsia (FD), diabetes mellitus, and neurological diseases. Diet may affect gastric emptying symptoms in patients with FD. We sought to determine the extent to which gastric emptying and symptoms of dyspepsia are influenced by caloric content in healthy subjects using ultrasonography. 32 healthy volunteers were given 2 meals with different caloric content in random order. Gastric emptying was determined using ultrasonography to measure antral area when fasting, and postprandially at intervals of 0, 10, 20, and 30 min. Dyspeptic symptoms including discomfort, nausea, and fullness were graded. The antral area following a high-caloric meal compared to a low-caloric meal was significantly increased at 0, 10, 20, and 30 min (P=0.0203,The caloric content of a meal influences gastric emptying. Using ultrasonography to measure the antral area helps us to assess gastric emptying and therefore to assess patients with functional dyspepsia.

Background The emerging adoption of the electronic medical record (EMR) in primary care enables clinicians and researchers to efficiently examine epidemiological trends in child health, including infant feeding practices. Methods We completed a population-based retrospective cohort study of 8815 singleton infants born at term in Ontario, Canada, April 2002 to March 2013. Newborn records were linked to the Electronic Medical Record Administrative data Linked Database (EMRALD™), which uses patient-level information from participating family practice EMRs across Ontario. We assessed exclusive breastfeeding patterns using an automated electronic search algorithm, with manual review of EMRs when the latter was not possible. We examined the rate of breastfeeding at visits corresponding to 2, 4 and 6 months of age, as well as sociodemographic factors associated with exclusive breastfeeding. Results Of the 8815 newborns, 1044 (11.8%) lacked breastfeeding information in their EMR. Rates of exclusive breastfeeding were 39.5% at 2 months, 32.4% at 4 months and 25.1% at 6 months. At age 6 months, exclusive breastfeeding rates were highest among mothers aged ≥40 vs. < 20 years (rate ratio [RR] 2.45, 95% confidence interval [CI] 1.62–3.68), urban vs. rural residence (RR 1.35, 95% CI 1.22–1.50), and highest vs. lowest income quintile (RR 1.18, 95% CI 1.02–1.36). Overall, immigrants had similar rates of exclusive breastfeeding as non-immigrants; yet, by age 6 months, among those residing in the lowest income quintile, immigrants were more likely to exclusively breastfeed than their non-immigrant counterparts (RR 1.43, 95% CI 1.12–1.83). Conclusions We efficiently determined rates and factors associated with exclusive breastfeeding using data from a large EMR database. Electronic supplementary material The online version of this article (10.1186/s12884-017-1633-9) contains supplementary material, which is available to authorized users.

Objectives Women from the Philippines form one of the largest immigrant groups to North America. Their newborns experience higher rates of preterm birth (PTB), and separately, small-for-gestational age (SGA) birth weight, compared with other East Asians. It is not known if Filipino women are at elevated risk of concomitant PTB and severe SGA (PTB–SGA), a pathological state likely reflective of placental dysfunction and neonatal morbidity. Methods We conducted a population-based study of all singleton or twin live births in Ontario, from 2002 to 2011, among immigrant mothers from the Philippines (n=27 946), Vietnam (n=15 297), Hong Kong (n=5618), South Korea (n=5148) and China (n=42 517). We used modified Poisson regression to generate relative risks (RR) of PTB-SGA, defined as a birth

In response to Thilagnathan’s comments,1 our paper identified several single risk factors that confer enough risk to justify aspirin prophylaxis in pregnancy (http://bit.ly/27Gw8LQ).2 For other risk factors, we recommend that two or more need to be present, again, based on our recent study. Maternal age over 40 years requires the presence of a second risk factor because its number needed to prevent was greater than 250. We agree that our systematic review could …

Objective To evaluate the influence of maternal and paternal country of origin on stillbirth risk. Methods We conducted a retrospective case–control study of all deliveries in Ontario between 2002 and 2011. We included 1373 stillbirths and 1 166 097 live births that had a documented country of origin for both parents. All newborns were singleton, born at between 20 and 42 weeks gestation, and weighed 250g to 7000g. We computed adjusted odds ratios (aOR) and 95% confidence intervals for the risk of stillbirth associated with parental country of origin. Models were adjusted for infant sex, maternal age, parity, marital status, and residential income quintile Results Compared with parent pairs in which both parents were Canadian-born, the aOR of stillbirth was higher whether immigrant parents came from the same country (aOR 1.32, 95% CI 1.16 to 1.51) or from different countries (aOR 1.34, 95% CI 1.08 to 1.65). The risk of stillbirth was highest for immigrant parents coming from the same country if that country had a high domestic stillbirth rate (aOR 1.60, 95% CI 1.30 to 1.97). Conclusion Maternal and paternal country of origin influences stillbirth risk Foreign-born couples, especially those originating from a country with a high stillbirth rate, are at greater risk Attention should focus on identifying genetic and environmental risk factors for stillbirth among specific immigrant groups, including developing prevention strategies for high-risk couples.

Background Preeclampsia (PE) increases maternal and perinatal morbidity and mortality. Based on a multitude of data from randomized clinical trials, clinical practice guidelines endorse using ASA to prevent PE in women who are “at risk.” However, data are lacking about the level of absolute risk to warrant starting ASA prophylaxis. Methods and Findings We present two approaches for objectively determining the minimum absolute risk for PE at which ASA prophylaxis is justified. The first is a new approach—the minimum control event rate (CERmin). The second approach uses a pre-existing concept—the minimum event rate for treatment (MERT). Here we show how the CERmin is derived, and then use the CERmin and the MERT to guide us to a reasonable risk threshold for starting a woman on ASA prophylaxis against PE based on clinical risk assessment. We suggest that eligible women need not be at “high risk” for preeclampsia to warrant ASA, but rather at some modestly elevated absolute risk of 6–10%. Conclusions Given its very low cost, its widespread availability, ease of administration and its safety profile, ASA is a highly attractive agent for the prevention of maternal and perinatal morbidity worldwide.

The practice of weighing newborns enables the distinction between healthy weight babies and those who are either small for gestational age (SGA) or large for gestational age (LGA). Because SGA and LGA newborns experience greater morbidity and mortality, such categorization potentially influences clinical care and the expectations of the child’s parents (1). There is evidence that, relative to non-SGA infants, those classified as SGA have significantly longer stays in neonatal intensive care units, extended use of continuous positive airway pressure ventilation, and more use of supplemental oxygen (2). In other words, correctly classifying an infant as SGA or LGA, or neither, is important. Birthweight percentile curves (or ‘charts’) are the classic method to visually determine whether a newborn is SGA, LGA, or of appropriate weight for gestational age and sex; however, it is not clear whether newborn centres use the same type of chart. Therefore, we surveyed all hospitals in Ontario that provide newborn care to determine which newborn percentile curve they use in their centre.

We thank Rafi for his comments on our paper.1 2 WHO, NICE, and the US Preventive Services Task Force (USPSTF) conclude, from systematic reviews, that aspirin prophylaxis is appropriate in high risk women.3 4 5 These guidelines list chronic kidney disease (CKD) and autoimmune diseases (eg, systemic lupus erythematosus; SLE) as risk factors designating women as “high risk” for pre-eclampsia. …

Supplemental Digital Content is available in the text, Alcohol contributes to intentional and unintentional injury. We explored on-premise licensed alcohol establishments (LAEs) and emergency medical service (EMS) ambulance calls. We completed a retrospective population-based study in the Region of Peel, Ontario, 2005 to 2014, where alcohol sales are tightly regulated and healthcare is universally available. We included participants age ≥ 19 years. Longitude–latitude coordinates of all 696 LAEs and all 267,477 EMS ambulance calls were ascertained, and then assigned to 1 of 1568 dissemination areas (DA) in Peel. Relative risks (RRs) described the association between density of on-premise LAEs (by DA deciles) and the rate of EMS calls, adjusted for material deprivation, and density of beer/liquor stores in each DA. There was a curvilinear relation between LAE density and EMS calls for trauma, rising from 45.3 per 1000 in DAs with no LAEs to 381.0 per 1000 in decile-10 (adjusted RR 7.83, 95% confidence interval [CI] 6.15–9.97). This relation was more pronounced for alcohol-focused LAEs, and highest among younger males. Calls for assault (RR 2.67, 95% CI 1.26–5.65) and intoxication (RR 4.00, 95% CI 1.41–11.38) were more likely on the last day of the month and the day thereafter, compared to 1 week prior. At 02:00 hours, when LAEs must stop selling alcohol, there was a considerable rise in assault-related calls in DAs with LAE but not in DAs without LAEs. On-premise LAEs contribute to EMS calls for trauma and assault, especially among young males, around last call, and when monthly pay cheques are cashed.

Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design Systematic review and meta-analysis of cohort studies. Data sources PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.