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.

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.

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.

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.

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.

Treatment Strategies in Early Rheumatoid Arthritis Methotrexate Management: Results From a Prospective Cohort.

OBJECTIVE: To assess real-world practice patterns surrounding treatment initiation and adjustments over time for methotrexate (MTX) and non-MTX-based treatment strategies in early rheumatoid arthritis (RA). METHODS: We studied a multicenter, incident early RA cohort (enrolled 2007-2017 within 1 year of symptoms) who fulfilled American College of Rheumatology/European League Against Rheumatism criteria. Adult patients with RA were eligible if treatment with MTX (± other disease-modifying antirheumatic drugs [DMARDs]) was initiated within 90 days of cohort entry. We compared time until treatment change for 4 initial MTX-based therapies and time to second treatment change after the first change. The definition of treatment change included changing of route for MTX monotherapy, adding or stopping a DMARD or biologic, and changing dose/frequency of a DMARD or biologic. RESULTS: There was great variability of treatment at initiation and during therapy adjustment. In 1,484 patients with early RA, the majority initiated MTX monotherapy (oral or subcutaneous [SC]). Patients receiving SC MTX monotherapy changed treatment less (45% versus 79%) and remained on treatment longer (hazard ratio [HR] 0.52 [95% confidence interval (95% CI) 0.4-0.67]) than those receiving oral MTX monotherapy. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those adults taking biologics and who were receiving triple therapy had a longer time without treatment change (HR 0.26 [95% CI 0.16-0.42] and HR 0.57 [95% CI 0.38-0.85], respectively). CONCLUSION: We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support the use of SC MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those patients initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy.

Peripartum cardiomyopathy with co-incident preeclampsia: A cohort study of clinical risk factors and outcomes among commercially insured women.

BACKGROUND: Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known. METHODS: We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM). RESULTS: We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups. CONCLUSION: Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM.

Care quality for rheumatoid arthritis patients in Quebec.

AIM: The aims of this study were to: (a) measure the proportion of CARTaGENE rheumatoid arthritis (RA) patients fulfilling pre-specified quality indicators (ie disease-modifying antirheumatic drug [DMARD] use, regular follow up, use of folate supplementation, use of vitamin D and calcium, exercise and smoking status); and (b) examine variation in DMARD use with respect to patient age, sex, education and income. METHODS: A cohort of RA patients was constructed based on the CARTaGENE survey and health administrative database. CARTaGENE is a large, established, population-based study which recruited 19 995 participants from four metropolitan regions in Quebec. Six quality indicators (QI) were assessed; four pertained to RA management and treatment received (use of DMARD therapy, annual medical visits, use of folate supplementation with methotrexate therapy, and use of calcium and vitamin D in steroid-exposed patients) and two pertained to lifestyle factors (physical activity and smoking cessation). QI were reported in terms of proportion of patients fulfilling them. Bayesian logistic regression analyses were preformed to investigate potential variation with DMARD use. RESULTS: Our cohort included 142 RA patients. The QI that pertain to RA pharmacotherapy and medical management ranged 60-80%. Regarding the QI focusing on lifestyle factors, 55% of patients reported performing moderate physical activity and only 16.6% reported current smoking. Results from the Bayesian logistic regression showed no definite associations between DMARD use and patient characteristics (age, education, income and sex). CONCLUSION: Our findings suggest a seemingly modest performance of Quebec's health-care system for RA patients, with respect to these QI.

Treatment Discontinuation and Clinical Events in Type 2 Diabetes Patients Treated with Dipeptidyl Peptidase-4 Inhibitors or NPH Insulin as Third-Line Therapy.

OBJECTIVE: To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas. METHODS: A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations. RESULTS: Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27-1.40) and hypoglycemia (HR: 2.98; 95% CI 2.72-3.28). Risk of cardiovascular events was similar across groups. CONCLUSIONS: This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

The Longterm Effect of Early Intensive Treatment of Seniors with Rheumatoid Arthritis: A Comparison of 2 Population-based Cohort Studies on Time to Joint Replacement Surgery.

OBJECTIVE: Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA). METHOD: Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000-2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated. RESULTS: Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95-0.98) and other DMARD (HR 0.98, 95% CI 0.97-0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2-3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC. CONCLUSION: Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery.

Medication Persistence of Disease-Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor Agents in a Cohort of Patients With Rheumatoid Arthritis in Brazil.

OBJECTIVE: To assess the use and persistence of anti-tumor necrosis factor (anti-TNF) versus disease-modifying antirheumatic drug (DMARD) therapies in patients with rheumatoid arthritis (RA) in Brazil. METHODS: This was a new-user cohort study of RA patients from 2003 to 2010, using administrative data. Individuals were classified as being persistent using a drug at the first year and the first 2 years after cohort entry, if they did not discontinue that drug during that period. Cox regression was used to identify potential determinants of discontinuation of therapy in each medication group. RESULTS: Among 76,351 patients, 14,313 were using anti-TNF (+/- DMARD) therapy. At the end of the first year of followup, 48.2% continued using anti-TNF (+/- DMARD) therapy compared to 42.6% who persisted with DMARDs only. At the end of the second year, 23.1% of anti-TNF (+/- DMARD) users and 19.3% of DMARD-only users continued with therapy. Infliximab users had the lowest persistence rates. Multivariate Cox regression analysis showed that among anti-TNF (+/- DMARD) users, higher discontinuation rates were observed in female patients, in patients with lower income (only at the first 2 years of followup), in nonresidents of the region with the highest Human Development Index (HDI) rates, in those with a higher comorbidity score, and in those enrolled in the 2003-2006 period. Among DMARD-only users, younger patients, patients with lower income, nonresidents in regions with high HDI, those with a higher comorbidity score, and those enrolled in the 2003-2006 period were also more likely to discontinue therapy. CONCLUSION: Brazilian patients with RA showed low rates of medication persistence for DMARDs and anti-TNF agents, particularly at the first 2 years of followup. Future work could determine what other factors might contribute to drug persistence in RA.

Opioid Use and Risk of Nonvertebral Fractures in Adults With Rheumatoid Arthritis: A Nested Case-Control Study Using Administrative Databases.

OBJECTIVE: To assess the risk of nonvertebral fractures in patients with rheumatoid arthritis (RA) who were exposed to opioids. METHODS: A population-based, nested case-control study was conducted using health services administrative databases (Quebec, Canada) from 1997 to 2012. Among RA patients, cases of nonvertebral fractures from 2007 to 2012 were identified using a validated algorithm. The date of the first fracture was the index date for the case and his/her matched control. Controls were selected using incidence density sampling and were matched 5:1 to cases for age, sex, and date of RA diagnosis. Opioid exposure was classified as current use, recent past use, remote past use, and nonuse. Conditional logistic regression was used to assess the association of nonvertebral fractures with opioid exposure, adjusting for comorbidity, indicators of RA severity, drugs influencing fracture risk, and health care utilization. RESULTS: In total, 1,723 cases and 8,046 controls were identified. Among these patients, 2,595 (722 cases and 1,873 controls) had been exposed to opioids. Current use (versus nonuse) increased the risk of nonvertebral fracture. Cumulative current use of opioids according to the quartile distribution was also associated with the risk of nonvertebral fracture: for continuous use for 1-20 days before the index date, odds ratio (OR) 11.49 (95% confidence interval [95% CI] 8.81-14.99); for 21-155 days, OR 1.75 (95% CI 1.31-2.33); for 156-355 days, OR 1.54 (95% CI 1.17-2.04); and for ≥356 days, OR 1.73 (95% CI 1.31-2.30). No association between the risk of nonvertebral fractures and recent past use or remote past use of opioids was observed. CONCLUSION: Among RA patients, the risk of nonvertebral fracture is increased in those treated with opioids.

Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study.

INTRODUCTION: Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada. METHODS: A cohort of new-onset RA patients was identified from Quebec's physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity. RESULTS: During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement. CONCLUSIONS: Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

Comparison of the Effect of Thiazide Diuretics and Other Antihypertensive Drugs on Central Blood Pressure: Cross-Sectional Analysis Among Nondiabetic Patients.

Thiazide diuretics (TDs) are a cost-effective first-line therapy for uncomplicated hypertension; however, they are less prescribed than other options. The authors aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to central blood pressure. Cross-sectional data from the Quebec CARTaGENE project was used. Nondiabetic hypertensive participants on monotherapy for hypertension were studied. Separate adjusted models were constructed to establish noninferiority of TDs to non-TD antihypertensive medications for central blood pressure measurements. Models included a set of potential confounders. Of the 1194 hypertensive participants, 7.4% were taking TDs. We found that TDs were comparable with non-TD antihypertensive medications for central systolic blood pressure (adjusted regression coefficient, 0.45; 95% confidence interval, -1.61 to 2.50). No differences in other central measurements were noted. The results provide additional support that TDs are at least as effective as other first-line medications for treating uncomplicated hypertension.

Humor in systemic lupus erythematosus.

OBJECTIVE: Humor has neurophysiological effects influencing the release of cortisol, which may have a direct impact on the immune system. Laughter is associated with a decreased production of inflammatory cytokines both in the general population and in rheumatoid arthritis (RA). Our objective was to explore the effects of humor on serum cytokines [particularly interleukin-6 (IL-6)] and cortisol levels in systemic lupus erythematosus (SLE), after a standard intervention (120 min of visual comedy). MATERIAL AND METHODS: We enrolled 58 females with SLE from consecutive patients assessed in the Montreal General Hospital lupus clinic. The subjects who consented to participate were randomized in a 1:1 ratio to the intervention (watching 120 min of comedy) or control group (watching a 120 min documentary). Measurements of cytokine and serum cortisol levels as well as 24-h urine cortisol were taken before, during, and after the interventions. We compared serum cytokine levels and serum and 24-h urine cortisol levels in the humor and control groups and performed regression analyses of these outcomes, adjusting for demographics and the current use of prednisone. RESULTS: There were no significant differences between the control and humor groups in demographics or clinical variables. Baseline serum levels of IL-6, IL-10, tumor necrosis factor-alpha, and B-cell activating factor were also similar in both groups. There was no evidence of a humor effect in terms of decreasing cytokine levels, although there was some suggestion of lowered cortisol secretion in the humor group based the 24-h urinary cortisol levels in a subgroup. CONCLUSION: In contrast to what has been published for RA, we saw no clear effects of humor in altering cytokine levels in SLE, although interesting trends were seen for lower cortisol levels after humor intervention compared with the control group.

Availability of data on adverse reactions to antiretroviral drugs in medical charts according to the Naranjo algorithm: an example of a Brazilian historical cohort.

BACKGROUND AND OBJECTIVE: Although not designed for research purposes, medical charts can be a unique source for obtaining information on long-term adverse drug reactions. This study aimed to assess the availability of key information on paper-based patient medical records needed to detect long-term adverse reactions to antiretroviral therapy (ART). METHODS: This is an ongoing historical cohort study carried out in three public HIV/AIDS referral centers in Belo Horizonte, Brazil. Medical charts of treatment-naïve HIV-infected adult patients initiating ART between 2001 and 2005 were reviewed for a follow-up period of up to 5 years after the first ART prescription. Descriptive analysis was performed by estimating the absolute and relative frequencies of selected variables. The Naranjo algorithm was employed to assess the availability of data on long-term adverse outcomes in medical charts. RESULTS: A total of 233 medical charts were eligible for study and 26.1% contained at least one long-term adverse reaction, corresponding to 45 cases of dyslipidemia (19.3%), 16 (6.9%) of lipodystrophy and 5 of type 2 diabetes mellitus (2.1%). Temporal relationship and ART switch could be better documented from medical charts. Information on reasons for ART switching and alternative causes for adverse reactions was very lacking. CONCLUSIONS: Specific tools should be developed and included in medical routines to improve adverse reaction reporting by physicians and other health professionals. This could be implemented simultaneously with the transition from paper to electronic medical charts in Brazil, facilitating the identification of long-term adverse reactions to antiretroviral drugs in epidemiological studies and in clinical practice.