Administrative data ICD-10 diagnostic codes identifies most lab-confirmed SARS-CoV-2 admissions but misses many discharged from the Emergency Department.

We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020-August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0-14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0-94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1-83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning.

Validity of hospital diagnostic codes to identify SARS-CoV-2 infections in reference to polymerase chain reaction results: a descriptive study.

BACKGROUND: In 2020, International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes were created for laboratory-confirmed SARS-CoV-2 infections. We assessed the operating characteristics of ICD-10 discharge diagnostic code U07.1 within the General Medicine Inpatient Initiative (GEMINI). METHODS: GEMINI assembles hospitalization data (including administrative ICD-10 discharge diagnostic codes, laboratory results and demographic data) from hospitals in Ontario, Canada. We studied adults (age ≥ 18 yr) admitted during 2020 and tested at least once for SARS-CoV-2 via polymerase chain reaction (PCR) during (or within 48 h before) hospitalization. With PCR results as the reference standard, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ICD-10 code U07.1 hospital discharge diagnostic codes. Analyses were stratified by demographic data, calendar period and timing of the first test (within or after 48 h of hospital admission). RESULTS: In 11 852 hospitalizations with at least 1 SARS-CoV-2 PCR test, 444 (3.7%) were positive. The sensitivity of code U07.1 to identify SARS-CoV-2 infection was 97.8%, specificity was 99.5%, PPV was 88.2% and NPV was 99.9%. Operating characteristics were similar in most stratified analyses, but the specificity and PPV were lower if the first SARS-CoV-2 test was done more than 48 hours after admission. INTERPRETATION: The sensitivity, specificity, PPV and NPV of code U07.1 were high. This supports using code U07.1 to identify SARS-CoV-2 infection in hospitalization data.

Importance of accounting for timing of time-varying exposures in association studies: Hydrochlorothiazide and non-melanoma skin cancer.

PURPOSE: Hydrochlorothiazide (HCTZ), a widely prescribed antihypertensive drug with photosensitising properties, has been linked with non-melanoma skin cancer (NMSC) risk. However, previous analyses did not fully explore if and how the impact of past HCTZ exposures accumulates with prolonged use and/or depends on time elapsed since exposures. Therefore, we used different models to more comprehensively assess how NMSC risk vary with HCTZ exposure, and explore how the results may depend on modeling strategies. METHODS: We used different parametric models with alternative time-varying exposure metrics, and the flexible weighted cumulative exposure model (WCE) to estimate associations between HCTZ exposures and NMSC risk in a population-based cohort of HCTZ users over 65 years old, in the province of Ontario, Canada. RESULTS: Among 3844 HCTZ users, 273 developed NMSC during up to 8 years of follow-up. In parametric models, based on all exposures, increased duration of past HCTZ use was associated with an increase of NMSC risk but cumulative dose showed no systematic association. Yet, WCE results suggested that only exposures taken 2.5-4 years in the past were associated with the current NMSC hazard. This finding led us to re-define the parametric models, which also confirmed that any HCTZ dose taken outside this time-window were not systematically associated with NMSC incidence. CONCLUSIONS: Our analyses illustrate how flexible modeling may yield new insights into complex temporal relationships between a time-varying drug exposure and risks of adverse events. Duration and recency of antihypertensive agents exposures must be taken into account in evaluating risk and benefits.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study.

BACKGROUND: Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). METHODS: We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. RESULTS: Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use. CONCLUSIONS: TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Sex Differences in the Effectiveness of Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Sacubitril-Valsartan for the Treatment of Heart Failure.

Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; P<0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; P<0.01; P interaction 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.

Skin Cancer and Hydrochlorothiazide: Novel Population-Based Analyses Considering Personal Risk Factors Including Race/Ethnicity.

BACKGROUND: Hydrochlorothiazide, a common antihypertensive, has photosensitive properties, potentially increasing skin cancer risk. We evaluated melanoma and nonmelanoma skin cancer among hydrochlorothiazide users with 3 different cohorts as each allows assessment of different potential cofounders/effect modifiers, including race/ethnicity. METHODS: We built 3 cohorts using IBM MarketScan Research Databases: Commercial and Encounters (>3.5 million individuals, 2010-2018), a subcohort with health risk assessment respondents (415, 330), and Medicaid (509, 767, 2011-2017). Adults (aged 18+ years) entered the respective cohort with a first-filled prescription (cohort entry) for hydrochlorothiazide (the exposure of interest) or angiotensin-converting enzyme (ACE) inhibitors (the active comparator), with ≥12 months of continuous enrollment with medical/pharmacy coverage at baseline. We excluded those who used hydrochlorothiazide/ACE inhibitor (including fixed-dose combination products) 12 months before cohort entry and those with prior skin cancer, HIV, or organ transplant. We compared the risk for hydrochlorothiazide versus ACE inhibitor using multivariate proportional hazards regression. RESULTS: Baseline characteristics were similar, aside from more Black individuals among hydrochlorothiazide users (43.3% [95% CI, 43.0%-43.6%]) than ACE inhibitor users (28.1% [95% CI, 27.9%-28.3%]). The hazard ratio (95% CI) for nonmelanoma skin cancer related to hydrochlorothiazide (versus ACE inhibitor) was 0.96 (0.91-1.00) in the Commercial cohort, 1.01 (0.77-1.32) for the health risk assessment subcohort, and 1.33 (0.77-2.29) for Medicaid. For melanoma, the respective hazard ratios were 1.07 (0.95-1.20), 0.85 (0.43-1.67), and 0.93 (0.51-1.67), respectively. CONCLUSIONS: Our evaluation using 3 different approaches, including adjustment for race/ethnicity, did not establish a clear difference between hydrochlorothiazide and ACE inhibitor in terms of skin cancer risk.

Prevalence of bruxism among college students: what are the associated factors? A cross-sectional study

Evaluate the prevalence of bruxism and to analyze what are the possible associated factors with this condition in students of a Brazilian university. Methods: This was a cross-sectional study, with a sample of 230 students randomly selected among undergraduate courses at a university center. The dependent variable was the presence of awake bruxism and sleep bruxism. The independent variables were sociodemographic factors, smoking, alcohol consumption, oral habits and stress perception (Perceived Stress Scale- PSS 14). Descriptive statistics and bivariate analysis were used. Results: The prevalence of awake bruxism was 28.7% and was associated with the independent variables: course (degree program), gum chewing habits, chin hand placing, facedown sleeping and one-side biting. Sleep bruxism had a 7.0% prevalence and displayed association with gum chewing, pens/pencils/objects biting, tongue/lips/cheeks biting, nails biting and one-side biting. Perceived stress was not associated with either type of bruxism. Conclusion: Bruxism has an important prevalence among university students, especially when distinguishing between awake bruxism and sleep bruxism

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.

The Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO): Comparisons between Quebec, Manitoba, Saskatchewan, and Alberta.

BACKGROUND: Given that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces. METHODS: CAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests. RESULTS: Almost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (p<0.001). Frequency of major malformations increased over time in Quebec (7-11%; p<0.001), Saskatchewan (5-11%; p<0.001), and Alberta (from 7-8%; p<0.001), and decreased in Manitoba (5-3%; p<0.001). Cardiovascular and musculoskeletal malformations were the most prevalent. INTERPRETATION: Medications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends.

Adapting SIMEX to correct for bias due to interval-censored outcomes in survival analysis with time-varying exposure.

Many clinical and epidemiological applications of survival analysis focus on interval-censored events that can be ascertained only at discrete times of clinic visits. This implies that the values of time-varying covariates are not correctly aligned with the true, unknown event times, inducing a bias in the estimated associations. To address this issue, we adapted the simulation-extrapolation (SIMEX) methodology, based on assessing how the estimates change with the artificially increased time between clinic visits. We propose diagnostics to choose the extrapolating function. In simulations, the SIMEX-corrected estimates reduced considerably the bias to the null and generally yielded a better bias/variance trade-off than conventional estimates. In a real-life pharmacoepidemiological application, the proposed method increased by 27% the excess hazard of the estimated association between a time-varying exposure, representing the 2-year cumulative duration of past use of a hypertensive medication, and the hazard of nonmelanoma skin cancer (interval-censored events). These simulation-based and real-life results suggest that the proposed SIMEX-based correction may help improve the accuracy of estimated associations between time-varying exposures and the hazard of interval-censored events in large cohort studies where the events are recorded only at relatively sparse times of clinic visits/assessments. However, these advantages may be less certain for smaller studies and/or weak associations.

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. METHODS: We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. RESULTS: Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. CONCLUSIONS: Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

Agreement in the CARTaGENE cohort between self-reported medication use and claim data.

OBJECTIVES: To describe the agreement of self-reported medication use with claim prescription records and to ascertain factors associated with agreement between the two data sources. METHODS: Baseline data on self-reported medication use was extracted from CARTaGENE, a cohort study in Quebec, Canada, and from the provincial health insurance records (dispensation database) of the same individuals. Kappa statistics were used to estimate concordance beyond chance between the two data sources. Logistic regression models were adjusted to estimate the association between agreement and selected individual's characteristics (sex, age, education, region, income, utilization of health care system, and comorbidities). RESULTS: Agreement between self-reported medication use and administrative data varied considerably across medication classes (kappa 0.54 for respiratory system and 0.91 for systemic hormonal preparations). Overall, agreement improved when a fixed time window of 90 days was used for exposure measurement. Sex, education level, frequency of health care use and the number of reported medications were associated with agreement. DISCUSSION: Overall, there was a reasonable agreement between the two data sources, but important variations were found for the different drug classes. These results could be used by researchers to more accurately assess drug exposures using real-world data, which are increasingly important to regulators.

Correction to: Epistemic and Political Confrontations Around the Public Policies to Fight COVID-19 Pandemic: What can Science Education learn from this episode?

[This corrects the article DOI: 10.1007/s11191-021-00193-3.].

Relative effectiveness of influenza vaccines in elderly persons in the United States, 2012/2013-2017/2018 seasons.

Influenza immunization protects seniors against influenza and its potentially serious complications. It is uncertain whether standard-dose (SD) quadrivalent vaccine offers better protection over other formulations in the elderly. In this study, we compared the effectiveness of SD-trivalent, high-dose (HD) trivalent, SD-quadrivalent, and adjuvanted trivalent vaccines in seniors (≥65 years) in a real-world setting. We selected over 200,000 individuals in each of 6 influenza seasons from 2012 to 2018 using MarketScan® databases. The two outcomes were hospitalization or emergency room (ER) visit due to (1) influenza or (2) pneumonia. Here, SD-quadrivalent was associated with higher risk of influenza-related hospitalization/ER visit (adjusted hazard ratio (aHR) 1.14 and 95% confidence interval (95% CI) 1.05-1.24) and of pneumonia-related hospitalization/ER visit (aHR 1.04 and 95% CI 1.01-1.07) vs. HD-trivalent. SD-trivalent followed similar trends compared to HD-trivalent (aHR 1.16 and 95% CI 1.06-1.27 for hospitalized/ER visit influenza; aHR 1.07 and 95% CI 1.05-1.10 for hospitalized/ER visit pneumonia). We could not demonstrate risk differences between SD vaccine formulations and between adjuvanted trivalent and one of the other three vaccines. Risk estimates slightly varied across seasons. These findings suggest that SD vaccine formulations vs. HD-trivalent were associated with higher risk of hospitalization/ER visit for influenza and pneumonia in seniors.

Epistemic and Political Confrontations Around the Public Policies to Fight COVID-19 Pandemic: What can Science Education learn from this episode?

Our purpose in this article is to discuss the roles for HPSS in Science Education considering the crisis of COVID-19, as well as to think what Science Education could look like beyond the pandemic. Considering the context of a pandemic as a starting point, we defend in this article the thesis that contours of public controversy involving COVID-19 bring elements that allow us to argue that Science Education needs to embrace perspectives that highlight politics as co-constitutive of science, and not in a subsidiary role to it. To defend this thesis, we begin with a theoretical framework based on arguments of science studies and from exemplary cases from history of science. Then, we analyze some of the public controversies surrounding COVID-19, in its most central aspects, trying to interpret how intertwining between science and politics took place. Brazilian case is analyzed in more details. Finally, based on educational scholarship and considering the previous discussions, we propose some implications for Science Education research and practices, both concerning the role of HPSS in its teaching and discussing critically boundaries of this research field.

Predictors of long-term use of prescription opioids in the community-dwelling population of adults without a cancer diagnosis: a retrospective cohort study.

BACKGROUND: Long-term opioid use is a known risk factor for opioid-related harms. We aimed to identify risk factors for and predictors of long-term use of prescription opioids in the community-dwelling population of adults without a diagnosis of cancer, to inform practice change at the point of care. METHODS: Using Quebec administrative claims databases, we conducted a retrospective cohort study in a random sample of adult members (≥ 18 yr) of the public drug plan who did not have a cancer diagnosis and who initiated a prescription opioid in the outpatient setting between Jan. 1, 2012, and Dec. 31, 2016. The outcome of interest was long-term opioid use (≥ 90 consecutive days or ≥ 120 cumulative days over 12 mo). Potential predictors included sociodemographic factors, medical history, characteristics of the initial opioid prescription and prescriber's specialty. We used multivariable logistic regression to assess the association between each characteristic and long-term use. We used the area under the receiver operating characteristic curve to determine the predictive performance of full and parsimonious models. RESULTS: Of 124 664 eligible patients who initiated opioid therapy, 4172 (3.3%) progressed to long-term use of prescription opioids. The most important associated factors in the adjusted analysis were long-term prescription of acetaminophen-codeine (odds ratio [OR] 6.30, 95% confidence interval [CI] 4.99 to 7.96), prescription of a long-acting opioid at initiation (OR 6.02, 95% CI 5.31 to 6.84), initial supply of 30 days or more (OR 4.22, 95% CI 3.81 to 4.69), chronic pain (OR 2.41, 95% CI 2.16 to 2.69) and initial dose of at least 90 morphine milligram equivalents (MME) per day (OR 1.24, 95% CI 1.04 to 1.47). Our predictive model, including only the initial days' supply and chronic pain diagnosis, had area under the curve of 0.7618. INTERPRETATION: This study identified factors associated with long-term prescription opioid use. Limiting the initial supply to no more than 7 days and limiting doses to 90 MME/day or less are actions that could be undertaken at the point of care.

Real-world analyses of therapy discontinuation of checkpoint inhibitors in metastatic melanoma patients.

The 'real-world' patient population of metastatic melanoma is not fully represented in clinical trials investigating checkpoint inhibitors. We described therapy discontinuation in an unselected population-based cohort of adults with metastatic melanoma who started therapy with pembrolizumab, nivolumab, or nivolumab/ipilimumab from January 2015 to August 2017. Therapy discontinuation was defined as a gap between doses beyond 120 days, and/or initiation of another cancer therapy. We estimated drug-specific rate ratios for therapy discontinuation adjusted for age, sex, comorbidities, health care use, and past cancer therapies. We included 876 metastatic melanoma patients initiating pembrolizumab (44.3%), nivolumab/ipilimumab (31.2%), and nivolumab (24.5%). At 12 months of follow-up, the probabilities of therapy discontinuation were 49.9% (95% confidence interval, CI 43.6-56.5) for pembrolizumab, 58.8% (95% CI 50.5-67.3) for nivolumab, and 59.2% (95% CI 51.7-66.8) for nivolumab/ipilimumab. Stratified analyses based on prior cancer therapy, brain metastases at baseline, and sex showed similar trends. In multivariable analyses, compared with pembrolizumab, patients starting nivolumab (rate ratio 1.38, 95% CI 1.08-1.77) or nivolumab/ipilimumab (rate ratio 1.30, 95% CI 1.02-1.65) were more likely to discontinue therapy. Our findings indicate frequent discontinuations of checkpoint inhibitors at one year. The lower discontinuation associated with pembrolizumab should be confirmed in further studies.

Novel glucose lowering agents are associated with a lower risk of cardiovascular and adverse events in type 2 diabetes: A population based analysis.

BACKGROUND: Recent randomized control trials have described a protective cardiovascular effect of novel glucose lowering drugs in patients at high cardiovascular risk. Whether these second-line agents have similar effects in the general population is unknown. We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy. METHODS: Retrospective cohort study using the MarketScan database (2011-2015). We selected T2DM individuals who were newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Cohort entry was defined by date of first prescription of the second-line agent. Time to first non-fatal cardiovascular or adverse event was compared using Cox regression models adjusted for confounders. RESULTS: Among 118,341 T2DM patients using metformin (mean age: 56), most were at low cardiovascular risk (4% with previous cardiovascular or cerebrovascular event). During a median follow-up of 10 months compared with sulfonylureas users, cardiovascular risk was lower in users of SGLT-2i (aHR = 0.61; 95% CI: 0.40-0.97), DPP-4i (aHR = 0.79; 95% CI: 0.69-0.90) and GLP-1a (aHR = 0.65; 95% CI: 0.48-0.89). Serious adverse events were rare but compared with sulfonylurea, the risk was lower in new users of novel glucose lowering agents. CONCLUSION: In our analyses, which included patients with and without prior cardiovascular disease, initiating novel glucose lowering drugs as second-line therapy for T2DM was associated with a lower risk of cardiovascular and adverse events than sulfonylurea initiation.

Antiphospholipid Antibody Testing in a General Population Sample from the USA: An Administrative Database Study.

We sought to characterized patterns of aPL testing in a large general population sample from the United States. Using Truven Health MarketScan laboratory data from 2010-2015 we identified individuals tested for lupus anticoagulant(LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein1(aGP1). Our research was approved by the McGill institutional review board (A04-M47-12B). We identified 33,456 individuals with at least one aPL test. Among these, only 6,391 (19%) had all three tests (LA, aCL, aGP1) performed. Confirmatory aPL testing was performed at least 12 weeks later in 77%, 45%, and 41% of initially positive LA, aCL, and aGP1, respectively. Of those re-tested after ≥12 weeks, only 255 (10.6%) were found to have a confirmatory positive aPL test. These findings highlight that aPL testing may often be incompletely performed. Further investigations will be required to better understand the low rate of a confirmatory positive aPL test ≥12 weeks after the initial test.

Sex Differences in Cardiovascular Effectiveness of Newer Glucose-Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus.

Background Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011-2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex-drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48-0.68; aHR-men: 0.82, 0.71-0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77-0.89; aHR-men: 0.85, 0.79-0.91) and SGLT-2i (aHR-women: 0.58, 0.46-0.74; aHR-men: 0.69, 0.57-0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73-0.89; aHR-men: 0.80, 0.71-0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78-0.87; aHR-men: 0.83, 0.78-0.87) and SGLT-2i (aHR-women: 0.68, 0.59-0.78; aHR-men: 0.67, 0.59-0.78) (all sex-drug interactions for adverse events P>0.05). Conclusions Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex.