Complications of the Arteriovenous Fistula: A Systematic Review.

The implementation of patient-centered care requires an individualized approach to hemodialysis vascular access, on the basis of each patient's unique balance of risks and benefits. This systematic review aimed to summarize current literature on fistula risks, including rates of complications, to assist with patient-centered decision making. We searched Medline from 2000 to 2014 for English-language studies with prospectively captured data on ≥100 fistulas. We assessed study quality and extracted data on study design, patient characteristics, and outcomes. After screening 2292 citations, 43 articles met our inclusion criteria (61 unique cohorts; n>11,374 fistulas). Median complication rates per 1000 patient days were as follows: 0.04 aneurysms (14 unique cohorts; n=1827 fistulas), 0.11 infections (16 cohorts; n>6439 fistulas), 0.05 steal events (15 cohorts; n>2543 fistulas), 0.24 thrombotic events (26 cohorts; n=4232 fistulas), and 0.03 venous hypertensive events (1 cohort; n=350 fistulas). Risk of bias was high in many studies and event rates were variable, thus we could not present pooled results. Studies generally did not report variables associated with fistula complications, patient comorbidities, vessel characteristics, surgeon experience, or nursing cannulation skill. Overall, we found marked variability in complication rates, partly due to poor quality studies, significant heterogeneity of study populations, and inconsistent definitions. There is an urgent need to standardize reporting of methods and definitions of vascular access complications in future clinical studies to better inform patient and provider decision making.

Long-term outcomes of thrombotic microangiopathy treated with plasma exchange: A systematic review.

With the adoption of plasma exchange as standard treatment for thrombotic microangiopathy (TMA), more patients are surviving and long-term outcomes have greater relevance. We conducted a systematic review to synthesize and evaluate the quality of evidence on long-term outcomes of TMA among adults treated with plasma exchange and to identify factors that may be associated with a worse long-term prognosis. We searched databases from 1980 to 2013 for eligible articles published in any language. We included studies that reported outcomes in at least ten adults with a history of TMA treated with plasma exchange and at least 6 months of follow-up. We abstracted data in duplicate and assessed the methodological quality of each study using an assessment tool developed based on recommended validity criteria. We screened 6672 articles, reviewed 213, and included 34 studies totaling 1182 patients (study median [range], 24 [10-118]). The mean (or median) follow-up ranged from 6 months to 13 years. The cumulative incidence of relapse and mortality was highly variable and ranged from 3 to 84 and 0 to 61%, respectively. The incidence of other outcomes across 10 studies also varied (outcomes included hypertension, kidney disease, preeclampsia, stroke, seizure, severe cognitive impairment, and depression); in three other studies, long-term neurocognitive function and health-related quality of life were significantly lower than in the general population. Patients who survive an episode of TMA may be susceptible to long-term vascular complications, but the magnitude of this risk and how to mitigate it remains unclear. Am. J. Hematol. 91:623-630, 2016. © 2016 Wiley Periodicals, Inc.

Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women.

BACKGROUND: The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic. METHODS: We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m(2)) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim-sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m(2)). RESULTS: The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36-0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25-0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses. INTERPRETATION: In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin.

Identifying Ontarians with Type 2 Diabetes Mellitus in Administrative Data: A Comparison of Two Case Definitions.

INTRODUCTION: This study compared two previously validated sensitive and specific diabetes case definitions to explore the impact of different classification methods in Ontario ICES administrative data. METHODS: This study included patients captured by the Ontario Diabetes Database with type 2 diabetes using either the sensitive cohort definition (≥ 2 physician visits for diabetes within 1 year or ≥ 1 drug claim for diabetes or ≥ 1 hospitalization with diabetes), or the specific cohort definition (≥ 3 physician visits for diabetes within 1 year), between October 1, 2013 to September 30, 2015. Each cohort's demographic and clinical features were described using descriptive analysis. RESULTS: Using sensitive and specific definitions, 1,093,812 and 783,228 patients with type 2 diabetes were identified, respectively. Overall, the demographic and clinical characteristics were similar between cohorts. Patients in the sensitive cohort had mean age of 64.1 years and were 52.4% male, compared to 64.8 years and 53.6% male in the specific cohort. In the sensitive and specific cohorts respectively, 64.4% and 55.7% of patients reported one-year mean HbA1c of < 7% (53 mmol/mol) and 25.3% and 31.5% reported levels between 7.0-8.5% (53-69 mmol/mol). CONCLUSIONS: Although sample sizes were different between sensitive and specific cohorts, demographic and clinical characteristics were similar.

Impact of the COVID-19 Pandemic on Adults With Type 2 Diabetes Care and Clinical Parameters in a Primary Care Setting in Ontario, Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes requires ongoing monitoring and care to prevent long-term adverse health outcomes. In Canada, quarantine restrictions were put into place to address the coronavirus-2019 (COVID-19) pandemic in March 2020. Primary care diabetes clinics limited their in-person services and were advised to manage type 2 diabetes (T2D) through virtual visits and reduce the frequency of routine diabetes-related lab tests and screening. METHODS: This retrospective cross-sectional study used de-identified patient records from a primary care electronic medical records database in Ontario, Canada, to identify people with T2D who had at least 1 health-care touchpoint between March 1, 2018, and February 28, 2021. Outcomes were described on a monthly or yearly basis: 1) number of people with primary care visits (in-person vs virtual); 2) number of people with referrals; 3) number of people with each of the vital/lab measures; and 4) results of the vital/lab measures. RESULTS: A total of 16,845 individuals with T2D were included. Compared with the pre-pandemic period, the COVID-19 period had a 16.8% reduction in the T2D population utilizing any primary care and an increase of 330.4% in the number of people with at least 1 virtual visit. Compared with the pre-pandemic period, fewer people had vital/lab measures in the pandemic period. However, among the people with the test results available, the average values for all tests were similar in the pre- and pandemic periods. CONCLUSION: Further research is needed to understand the impact of the reduction of in-person clinical care on the entire population with T2D.

Impact of the COVID-19 Pandemic on Antihyperglycemic Prescriptions for Adults With Type 2 Diabetes in Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality. METHODS: This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. "New-to-molecule" patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D. RESULTS: A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020. CONCLUSION: The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D.

An institutional report of heparin induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse. OBJECTIVE: We report our institution's incidence and outcomes of HIT-II in aSAH patients. METHODS: We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA). RESULTS: 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores. CONCLUSION: Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.

A survey of physician experience and treatment satisfaction prescribing once-weekly semaglutide injections for patients with type 2 diabetes in Canada.

We assessed physicians' experiences of prescribing once-weekly (OW) semaglutide to patients with type 2 diabetes (T2D) in Canada. Physicians who had prescribed OW semaglutide to ≥2 patients with T2D in the past 12 months and had been doing so for ≥3 months were surveyed during 1-17 October 2018. Prescribing reasons, treatment satisfaction and reasons for discontinuation were assessed. Of the 50 participants, 72% and 54% were prescribed OW semaglutide due to its superior glycemic control and effect on weight, respectively. Most physicians were more satisfied with injection frequency (62%), effect on weight (60%), achieving HbA1c target (54%) and therapy simplicity (50%) with OW semaglutide versus other glucagon-like peptide-1 receptor agonists. Treatment discontinuations in 13% of OW semaglutide-treated patients were reported by physicians, primarily due to gastrointestinal symptoms (70%). The survey suggests that physicians are satisfied with the OW semaglutide clinical effects. Video Abstract: http://links.lww.com/CAEN/A34.

Cost-Effectiveness of Once-Weekly Semaglutide 1 mg versus Canagliflozin 300 mg in Patients with Type 2 Diabetes Mellitus in a Canadian Setting.

OBJECTIVE: Our objective was to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin from the healthcare payer and societal perspectives in Canada. METHODS: Head-to-head data from the SUSTAIN 8 randomised trial (NCT03136484) were extrapolated over 40 years using economic simulation modelling. The cost-effectiveness of once-weekly semaglutide 1 mg versus canagliflozin 300 mg for treating T2DM was estimated using the Swedish Institute for Health Economics-Diabetes Cohort Model (IHE-DCM) and the Economic and Health Outcomes Model of T2DM (ECHO-T2DM). Unit costs and disutility weights capturing treatments and key macro- and microvascular complications were sourced from the literature to best match the Canadian setting. A probabilistic base-case simulation and sensitivity analyses were conducted. RESULTS: Once-weekly semaglutide 1 mg was associated with reductions in macro- and microvascular complications, yielding incremental cost-effectiveness ratios (ICERs) of (Canadian dollars [CAD]) CAD16,392 and 18,098 per incremental quality-adjusted life-year (QALY) gained versus canagliflozin 300 mg for IHE-DCM and ECHO-T2DM, respectively, from a healthcare payer perspective. Accounting for productivity loss as well, ICERs were CAD14,127 and 13,188 per QALY gained for IHE-DCM and ECHO-T2DM, respectively, from a societal perspective. Sensitivity analyses confirmed that the base-case results were robust to changes in input parameters and assumptions used. CONCLUSIONS: At a willingness-to-pay threshold of CAD50,000 per QALY gained, once-weekly semaglutide 1 mg was cost-effective over 40 years versus once-daily canagliflozin 300 mg for the treatment of T2DM in patients failing to maintain glycemic control with metformin alone.

Real-world persistence with liraglutide 3.0 mg for weight management and the SaxendaCare® patient support program.

OBJECTIVE: Weight management medications can significantly increase patients' chances of achieving a clinically meaningful weight loss if patients persist with treatment. This retrospective observational study of de-identified medical records of 311 patients is the first real-world study examining persistence with liraglutide 3.0 mg in Canada, and also investigates associations between the SaxendaCare® patient support program and persistence and weight loss. METHODS: Overall persistence was assessed, as well as associations of enrollment in SaxendaCare®, persistence and weight loss. RESULTS: Overall mean (standard deviation) persistence with liraglutide 3.0 mg was 6.3 (4.1) months, and 67.5% (n = 210) and 53.7% (n = 167) of patients persisted for ≥4 and ≥ 6 months, respectively. Enrollment in SaxendaCare® was associated with significantly longer persistence with liraglutide 3.0 mg and greater weight loss. Patients enrolled in SaxendaCare® (n = 119) persisted for 7.9 (4.0) versus 5.2 (3.8) months for those not enrolled (n = 184) (p < 0.001), and had significantly greater percent weight loss after 6 months regardless of the duration of their persistence (-7.9% vs -5.5% from baseline, p < 0.01). CONCLUSIONS: These findings suggest that, in clinical settings, persistence with liraglutide 3.0 mg can exceed 6 months, and that enrolling in SaxendaCare® may be associated with comparatively longer persistence and, regardless of persistence, greater weight loss.

Weight loss and persistence with liraglutide 3.0 mg by obesity class in the real-world effectiveness study in Canada.

OBJECTIVE: Liraglutide 3.0 mg is associated with clinically significant weight loss in clinical trials, but real-world data are lacking. In this analysis, weight loss and persistence outcomes with liraglutide 3.0 mg were assessed across obesity classes, in a real-world clinical setting. METHODS: Secondary analysis of an observational, retrospective study of liraglutide 3.0 mg for weight management (as adjunct to diet and exercise) at six Wharton Medical Clinics in Canada. Patients were categorized by body mass index (BMI, kg/m2) into obesity class I (BMI 30-34.9); class II (BMI 35-39.9); and class III (BMI ≥40). Change in weight, categorical weight loss, time to maintenance dose (defined as the time to reach the full liraglutide 3.0 mg maintenance dose) and persistence were assessed for each class and for differences between classes. RESULTS: Of 308 patients, 70 (22.7%) had obesity class I, 83 (26.9%) obesity class II and 155 (50.3%) obesity class III. Similar percentage change in weight was observed between obesity classes (mean [standard deviation, SD]: -7.0% [6.0], -6.6% [6.0] and -6.1% [5.0], respectively; p = .640), and similar proportions achieved ≥5% weight loss (60.4%, 62.0% and 55.3%, respectively; p = .717) at 6 months. Mean time to maintenance dose (SD) was 64.2 (56.4) d, 76.4 (56.3) d and 71.4 (54.5) d for obesity classes I, II and III, respectively (p = .509). Persistence with medication was also similar between obesity classes (p = .358). CONCLUSIONS: These findings suggest that real-world treatment with liraglutide 3.0 mg, regardless of obesity class, is associated with similar clinically significant weight loss, time to maintenance dose and medication persistence.

Cost Effectiveness of Once-Weekly Semaglutide Versus Once-Weekly Dulaglutide in the Treatment of Type 2 Diabetes in Canada.

OBJECTIVE: The aim of this study was to assess the cost effectiveness of semaglutide versus dulaglutide, as an add-on to metformin monotherapy, for the treatment of type 2 diabetes (T2D), from a Canadian societal perspective. METHODS: The Swedish Institute for Health Economics Cohort Model of T2D was used to assess the cost effectiveness of once-weekly semaglutide (0.5 or 1.0 mg) versus once-weekly dulaglutide (0.75 or 1.5 mg) over a 40-year time horizon. Using data from the SUSTAIN 7 trial, which demonstrated comparatively greater reductions in glycated hemoglobin (HbA1c), body mass index and systolic blood pressure with semaglutide, compared with dulaglutide, a deterministic base-case and scenario simulation were conducted. The robustness of the results was evaluated with probabilistic sensitivity analyses and 15 deterministic sensitivity analyses. RESULTS: The base-case analysis indicated that semaglutide is a dominant treatment option, compared with dulaglutide. Semaglutide was associated with lower total costs (Canadian dollars [CAN$]) versus dulaglutide for both low-dose (CAN$113,287 vs. CAN$113,690; cost-saving: CAN$403) and high-dose (CAN$112,983 vs. CAN$113,695; cost-saving: CAN$711) comparisons. Semaglutide resulted in increased quality-adjusted life-years (QALYs) and QALY gains, compared with dulaglutide, for both low-dose (11.10 vs. 11.07 QALYs; + 0.04 QALYs) and high-dose (11.12 vs. 11.07 QALYs; + 0.05 QALYs) comparisons. The probabilistic sensitivity analysis showed that for 66-73% of iterations, semaglutide was either dominant or was considered cost effective at a willingness-to-pay threshold of CAN$50,000. CONCLUSIONS: From a Canadian societal perspective, semaglutide may be a cost-effective treatment option versus dulaglutide in patients with T2D who are inadequately controlled on metformin monotherapy.

Real-World Clinical Effectiveness of Liraglutide 3.0 mg for Weight Management in Canada.

OBJECTIVE: Real-world clinical effectiveness of liraglutide 3.0 mg, in combination with diet and exercise, was investigated 4 and 6 months post initiation. Changes in absolute and percent body weight were examined from baseline. METHODS: A cohort of liraglutide 3.0 mg initiators in 2015 and 2016 was identified from six Canadian weight-management clinics. Post initiation values at 4 and 6 months were compared with baseline values using a paired t test. RESULTS: The full cohort consisted of 311 participants, with 210 in the ≥ 4-month persistence group and 167 in the ≥ 6-month persistence group. Average baseline BMI was 40.7 kg/m2 , and weight was 114.8 kg. There was a significant change in body weight 6 and 4 months after initiation of treatment in persistent subjects (≥ 6-month: -8.0 kg, P < 0.001; ≥ 4-month: -7.0 kg, P < 0.001) and All Subjects, regardless of persistence (-7.3 kg; P < 0.001). Percentage change in body weight from baseline was -7.1% in the ≥ 6-month group and -6.3% in the ≥ 4-month group, and All Subjects lost 6.5% body weight. Of participants in the ≥ 6-month group, 64.10% and 34.5% lost ≥ 5% and > 10% body weight, respectively. CONCLUSIONS: In a real-world setting, liraglutide 3.0 mg, when combined with diet and exercise, was associated with clinically meaningful weight loss.

Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD.

BACKGROUND AND OBJECTIVES: Current dosing recommendations for cephalosporin antibiotics are on the basis of pharmacokinetic studies and are frequently ignored in practice. This study was undertaken to investigate the clinical outcomes of failing to dose-reduce cephalosporin antibiotics in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective cohort study conducted in Ontario, Canada using linked population-based health care databases. Nine thousand three hundred forty-seven outpatients (median age 83; interquartile range, 77-88 years; 57% women) with an eGFR<30 ml/min per 1.73 m2 and no prior history of dialysis were dispensed oral cephalexin, cefuroxime, or cefprozil between April of 2007 and March of 2016. Two thirds of the patients (6253 of 9347) received a higher than recommended daily dose of cephalexin (>1000 mg), cefuroxime (>500 mg), or cefprozil (>500 mg). The primary outcome was a hospital encounter (emergency room visit or hospital admission) with a condition listed as a possible side-effect of cephalosporins. Secondary outcomes were antibiotic treatment failure and all-cause mortality. All measures were assessed in the 30 days after cephalosporin initiation. RESULTS: Patients who received a higher than recommended dose of a cephalosporin antibiotic were similar in multiple indicators of baseline health to patients who received a reduced dose. Overall, 6% of patients presented to hospital with a possible cephalosporin side-effect, 13% failed antibiotic treatment, and 3% died. Compared with a reduced dose, receiving a higher dose of antibiotic was not associated with a different rate of side-effects (adjusted odds ratio, 1.00; 95% confidence interval, 0.84 to 1.20), treatment failure (1.01; 0.88 to 1.15), or death (0.99; 0.76 to 1.29). CONCLUSIONS: In this study we failed to demonstrate any association between the dose of cephalosporin antibiotic administered to elderly patients with CKD and the risk of side-effects leading to hospitalization, treatment failure, or mortality.

Perceptions of barriers to effective obesity management in Canada: Results from the ACTION study.

Obesity is a chronic disease with a significant and growing impact on Canadians. The "Awareness, Care and Treatment In Obesity MaNagement" (ACTION) Study investigated perceptions, attitudes and perceived barriers to obesity management among Canadian people with obesity (PwO), healthcare providers (HCPs) and employers. In this study adult PwO (body mass index ≥30 kg/m2 , based on self-reported height/weight), HCPs (physicians and allied HCPs managing PwO) and employers (≥20 employees; offering health insurance), completed online surveys between 3 August and 11 October 2017 in a cross-sectional design. Survey respondents (N = 2545) included 2000 PwO, 395 HCPs and 150 employers. Obesity was viewed as a "chronic medical condition" by most PwO (60%), HCPs (94%) and employers (71%) and deemed to have a large impact on overall health (74%, 78%, 81%, respectively). Many PwO (74%) believed weight management was their own responsibility. While PwO (55%) reportedly knew how to manage their weight, only 10% reported maintaining ≥10% weight reduction for >1 year. Despite low success rates, the most commonly reported effective long-term weight loss methods tried and/or recommended were "improvements in eating habits" (PwO 38%; HCP 63%) and "being more active" (PwO 39%; HCP 54%). PwO and HCPs reported very different perceptions of the quality and content of their interaction during obesity management discussions. These findings highlight the communication gaps and misunderstanding between PwO, HCPs and employers. This underscores the importance of, and need for, evidence-based management of obesity and a collaborative approach and understanding of the complex nature of this chronic disease.

A matched case-control study to assess the association between non-steroidal anti-inflammatory drug use and thrombotic microangiopathy.

Several case reports suggest that non-steroidal anti-inflammatory drug (NSAID) use is associated with development of thrombotic microangiopathy (TMA). We conducted a matched population-based case-control study using linked administrative healthcare data in Ontario, Canada to assess the relationship between TMA hospitalization and recent exposure to prescription NSAIDs versus acetaminophen (acetaminophen was chosen as the referent drug because it has no known association with TMA). Cases and controls were drawn from a source population of adults who filled a prescription for either NSAIDs or acetaminophen between 1991 and 2015 (restricted to adults with prescription drug benefits [n = 3.6 million]). We identified 44 eligible cases with a hospital admission for incident TMA and a recent prescription for NSAIDs or acetaminophen. We successfully matched 38 cases (1:4) to 152 controls without TMA on demographics, risk factors for TMA, and indications for NSAID use. Cases and controls were similar with respect to age (71 years) and sex (63% women); however, on average, cases had more comorbidities than controls (12 vs. 14; p<0.05) and more primary care visits in the year before the index date (19 vs. 12; p<0.05). Cases were significantly less likely than controls to have received a recent prescription for NSAIDs (19/38 [50%] vs. 115/152 [76%], respectively; adjusted odds ratio 0.37, 95% confidence interval: 0.16 to 0.84). Results were similar in several sensitivity analyses. Overall, the results of this study do not support a harmful association between NSAID use and the development of TMA.