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.

Associations between low- and high-dose oral fluconazole and pregnancy outcomes: 3 nested case-control studies.

BACKGROUND: While topical azoles are the first-line treatment for fungal infections, oral fluconazole is frequently used during pregnancy. We aimed to assess the effect of exposure to low and high doses of fluconazole during pregnancy on the occurrence of spontaneous abortions, major congenital malformations and stillbirths. METHODS: Within the Quebec Pregnancy Cohort (1998-2015), we identified women exposed to low- (≤ 150 mg) and high-dose (> 150 mg) fluconazole, and women who were not exposed. For each case of spontaneous abortion or stillbirth, up to 5 controls were randomly selected using an incidence density sampling method matched on gestational age at diagnosis of spontaneous abortion or stillbirth (index date) and the year of the last menstrual period. For cases of major congenital malformation, we considered all liveborn babies as controls. Generalized estimation equation models were used to analyze the 3 main outcomes separately. RESULTS: Within a cohort of 441 949 pregnancies, 320 868 pregnancies were included in the analyses of spontaneous abortions, 226 599 of major congenital malformations and 7832 of stillbirths. Most (69.5%) women exposed to fluconazole in pregnancy received the common single therapeutic dose of 150 mg (low dose); the remainder received a dose of > 150 mg (high dose). Use of oral fluconazole during early pregnancy was associated with an increased risk of spontaneous abortion compared with no exposure (adjusted odds ratio [OR] for 345 cases exposed to low-dose treatment 2.23, 95% confidence interval [CI] 1.96-2.54; adjusted OR for 249 cases exposed to high-dose treatment 3.20, 95% CI 2.73-3.75). Exposure to fluconazole during the first trimester did not increase the risk of overall major congenital malformations; however, exposure to a high dose during the first trimester was associated with an increased risk of cardiac septal closure anomalies (adjusted OR 1.81, 95% CI 1.04-3.14; 13 exposed cases) compared with no exposure. No association was found between exposure to fluconazole during pregnancy and the risk of stillbirth. INTERPRETATION: Any maternal exposure to fluconazole during pregnancy may increase risk of spontaneous abortion and doses higher than 150 mg during the first trimester may increase risk of cardiac septal closure anomalies.

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.

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.

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.

Drug-drug interactions associated with length of stay and cost of hospitalization.

PURPOSE: To evaluate the prevalence of drug-drug interactions (DDI) in prescriptions of hospitalized patients and to identify risk factors associated. METHODS: A retrospective cross-sectional analysis of prescription data and medical records from a public hospital in Brazil was conducted to identify potential DDI. An inappropriate drug combination was identified and classified with a standard drug interaction source. The main diagnoses were classified with Charlson Comorbidity Index (CCI). Sex, age, polypharmacy and length of stay, among other variables, were correlated with the frequency of potential DDI. RESULTS: The study included 589 patients and 3,585 prescriptions. Thirty-seven percent of the patients were exposed to at least one potential interaction during their stay in the hospital. The most frequent interacting pair was Digoxin+Furosemide (11%). In univariate analysis, several variables were associated with DDI, including sex, age, number of prescribed drugs, length and cost of hospitalization and CCI. Multivariate analysis showed that the adjusted odds of being prescribed a potential DDI among patients in polypharmacy was almost five-fold that of patients taking less than five drugs. Further, length of stay, CCI and cost of hospitalization were independently associated with DDI. CONCLUSION: Analysis of prescription data found that a substantial number of potential DDI were identified. Results of this study indicate that DDI is associated with number of prescribed drugs, increased duration of stay in the hospital and cost, which suggest that DDI are a significant clinical and economic problem. Potential damage to patients could be avoided.

A Systematic Review of Interventions and Programs Targeting Appropriate Prescribing of Opioids.

BACKGROUND: Canada and the United States have the highest levels of prescription opioid consumption in the world. In an attempt to curb the opioid epidemic, a variety of interventions have been implemented. Thus far, evidence regarding their effectiveness has not been consolidated. OBJECTIVES: The objectives of this study were to: 1) identify interventions that target opioid prescribing; 2) assess and compare the effectiveness of interventions on opioid prescription and related harms; 3) determine the methodological quality of evaluation studies. STUDY DESIGN: The study involved a systematic review of the literature including bibliographical databases and gray literature sources. SETTING: Systematic review including bibliographical databases and gray literature sources. METHODS: We searched MEDLINE, Embase, and LILACS databases from January 1, 2005 to September 23, 2016 for any intervention that targeted the prescription of opioids. We also examined websites of relevant organizations and scanned bibliographies of included articles and reviews for additional references. The target population was that of all health care providers (HCPs) or users of opioids with no restriction on indication. Endpoints were those related to process (implementation), outcomes (effectiveness), or impact. Sources were screened independently by 2 reviewers using pre-defined eligibility criteria. Synthesis of findings was qualitative; no pooling of results was conducted. RESULTS: Literature search yielded 12,278 unique sources. Of these, 142 were retained. During full-text review, 75 were further excluded. Searches of the gray literature and bibliographies yielded 49 additional sources. Thus, a total of 95 distinct interventions were identified. Over half consisted of prescription monitoring programs (PMPs) and mainly targeted HCPs. Evaluation studies addressed mainly opioid prescription rate (30.6%), opioid use (19.4%), or doctor shopping or diversion (9.7%). Fewer studies considered overdose death (9.7%), abuse (9.7%), misuse (4.2%), or diversion (5.6%). Study designs consisted of cross-sectional surveys (23.3%), pre-post intervention (26.7%), or time series without a comparison group (13.3%), which limit the robustness of the evidence. Although PMPs and policies have been associated with a reduction in opioid prescription, their impact on appropriateness of use according to clinical guidelines and restriction of access to patients in need is inconsistent. Continuing medical education (CME) and pain management programs were found effective in improving chronic pain management, but studies were conducted in specific settings. The impact of interventions on abuse and overdose-death is conflicting. LIMITATIONS: Due to the very large number of publications and programs found, it was difficult to compare interventions owing to the heterogeneity of the programs and to the methodologies of evaluation studies. No assessment of publication bias was done in the review. CONCLUSIONS: Evidence of effectiveness of interventions targeting the prescription of opioids is scarce in the literature. Although PMPs have been associated with a reduction in the overall prescription rates of Schedule II opioids, their impact on the appropriateness of use taking into consideration benefits, misuse, legal and illegal use remains elusive. Our review suggests that existing interventions have not addressed all determinants of inappropriate opioid prescribing and usage. A well-described theoretical framework would be the backdrop against which targeted interventions or policies may be developed. KEY WORDS: Opioid, prescription, abuse, misuse, diversion, interventions, prescription monitoring programs.

Restrictive measure for the commercialization of antimicrobials in Brazil: results achieved.

OBJECTIVE: To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS: A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS: The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006-0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003-0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS: The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

Direct-Acting Antivirals for Hepatitis C: Predictors of Early Discontinuation in the Real World.

BACKGROUND: The treatment for hepatitis C virus (HCV) infection has evolved over time, and direct-acting antivirals (DAA) have revolutionized HCV therapy. OBJECTIVES: To (a) assess early treatment discontinuation and (b) identify predictors of early discontinuation in a cohort of patients receiving second-generation DAAs. METHODS: We identified HCV patients newly prescribed simeprevir/sofosbuvir (SIM/SOF), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR), and glecaprevir/pibrentasvir (GLE/PIB) between 2014 and 2017. Early discontinuation was defined as duration of therapy less than 8 weeks. Multivariable logistic regression was performed to evaluate the association of drug regimens and potential predictive factors to early discontinuation. RESULTS: We identified 26,098 DAA-treated patients: 67.8% with LDV/SOF, 9.9% with OPrD, 8.5% with SIM/SOF, 7.8% with SOF/VEL, 5.2% with EBR/GZR, and 0.8% with GLE/PIB. With approval of new therapies in 2016 and 2017, use of OPrD, LDV/SOF, and SIM/SOF declined substantially. At baseline, there was some heterogeneity of past HCV drug use and comorbidity across groups; patients on SIM/SOF had the highest frequency of previous interferon, cirrhosis, and decompensated cirrhosis. Most HCV patients received therapy for 8-12 weeks; fewer patients went through 16-week and 24-week therapy courses. Early discontinuation rates (95% CI) were 7.1% (6.0-8.2) for SIM/SOF, 3.2% (2.9-3.5) for LDV/SOF, 9.6% (8.5-10.7) for OPrD, 3.1% (2.3-3.8) for SOF/VEL, 4.2% (3.1-5.3) for EBR/GZR, and 2.5% (0.3-4.7) for GLE/PIB. In multivariable analyses, versus OPrD, patients starting other drug regimens were less likely to discontinue therapy early. Early discontinuation was more common in women, patients with baseline anemia, and Medicare and Medicaid patients. CONCLUSIONS: These real-world data confirm low rates of early discontinuation in users of second-generation DAAs. Future research focusing on socio-economic and sex/gender issues may help further optimize care for patients with HCV. DISCLOSURES: This study was funded by the Canadian Institutes of Health Research. Klein has received grants for investigator-initiated trials from ViiV Healthcare, Janssen, Gilead, and Merck, as well as consulting fees from ViiV Healthcare, Merck, and AbbVie. Feld has received research support and/or scientific consulting fees from AbbVie, Contravir, Enanta, Gilead, Janssen, Merck, and Wako. All other authors have no conflicts of interest to declare. Results from this study were presented as a poster at the 34th International Conference of Phamacoepidemiology and Therapeutic Risk Management; August 22-26, 2018; Prague, Czech Republic.

Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study.

BACKGROUND: Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. METHODS: We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics. The date of first prescription was defined as the cohort entry. The therapy was considered effective if all of the following criteria from a claims-based algorithm were achieved at the first year of follow-up: high adherence, no biologic or tofacitinib switch or addition, no DMARD switch or addition, no increase in dose or frequency of index drug, no more than one glucocorticoid joint injection, and no new/increased oral glucocorticoid dose. The safety outcome was serious infections requiring hospitalization. Non-TNF biologics comprised the reference group. RESULTS: We included 21,832 patients with RA, including 0.8% treated with tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and 19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF biologics appeared to have similar effectiveness rates, whereas DMARD initiators were less effective than non-TNF biologics. We could not clearly establish if tofacitinib was associated with a higher rate of serious infections. CONCLUSIONS: In patients with RA previously treated with methotrexate, our comparisons of tofacitinib with non-TNF biologics, though not definitive, did not demonstrate differences with respect to hospitalized infections or effectiveness.

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population-based study.

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80-0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI, 1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a strong rationale for choosing TDs as first-line monotherapy for the control of hypertension.

[Use of medications by elderly Brazilian retirees: 1--methodology and response rates of a multicenter survey]. / Utilização de medicamentos por aposentados brasileiros: 1--metodologia e resultados de cobertura de inquérito multicêntrico.

This paper reports methodological aspects and response rates of a survey with the main objective of describing the drug utilization profile of retirees of the Institute of National Social Security of Brazil, 60 years of age or older, in three simple random samples: Brazil (countrywide), Belo Horizonte municipality, and Rio de Janeiro municipality. This cross-sectional study employed two approaches: mail (self-report questionnaires) and home interviews (questionnaires completed by interviewers). This strategy allowed evaluation of response agreement between the mail and home interview approaches. In the national sample of 3,000 individuals, 1,025 only responded to the self-report questionnaire. Despite this the low response rate, there was reasonable resemblance between respondents and non-respondents, suggesting that this sample is representative of the target population. In Belo Horizonte and Rio de Janeiro the initial samples of 800 individuals were replicated for both approaches, mail and home interview. The response rates to the mail surveys were 46.8% and 34.4% in Belo Horizonte and Rio de Janeiro, respectively. The response rates to the home interviews were 80.3% and 70.7% in Belo Horizonte and Rio de Janeiro, respectively, after unavoidable attrition.

Costs of Drug Therapy in Patients with Ankylosing Spondylitis in Brazil.

INTRODUCTION: The Brazilian Public Health System offers free-of-charge drug treatment for ankylosing spondylitis (AS) to all Brazilian citizens. We report here the first population-based cohort study on patients with AS in Brazil. The aim of this study was to evaluate the costs of the tumour necrosis factor (anti-TNF) blockers and disease-modifying antirheumatic drugs (DMARDs) that were used in the treatments of patients with AS in Brazil between March 2010 and September 2013. METHODS: A retrospective cohort study was performed using administrative databases. All patients with a diagnosis of AS who were aged 18 years or older and had been dispensed anti-TNF or DMARDs were included in the analysis. The cost analysis was carried out from the health system perspective, and the results were described as median monthly cost per capita and the annual cost over the study period. RESULTS: A search of the databases identified 1251 patients with AS who were treated during the study period, of whom 63.3% were male; the median age was 41 years. During the study period, 78.0% of patients initiated treatment with anti-TNF drugs and 22.0% with DMARDs. The median monthly cost per capita was US$ 1650 for anti-TNF therapy and US$ 25 for treatment with DMARDs. Among the anti-TNF drugs, therapy with etanercept was associated with the lowest cost per patient, followed by adalimumab and infliximab. No difference in monthly cost was observed in relation to gender and age. CONCLUSION: The cost per patient of treating AS in this study cohort was lower with etanercept than with adalimumab and infliximab. These results highlights the economic burden of treating patients with AS.

Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS: This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients' chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS: The study included 11,642 patients with rheumatoid arthritis - 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD - and 1,251 patients with ankylosing spondylitis - 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS: A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher persistence for DMARD in patients with rheumatoid arthritis as compared to ankylosing spondylitis. OBJETIVO: Avaliar a persistência do tratamento em pacientes com artrite reumatoide e espondilite anquilosante que iniciaram terapia com medicamentos modificadores do curso da doença (MMCD) e agentes bloqueadores do fator de necrose tumoral (anti-TNF). MÉTODOS: Este estudo de coorte retrospectiva de julho de 2008 a setembro de 2013 avaliou a persistência na terapia, definida como o tempo do início até a descontinuação, permitindo-se um intervalo de até 30 dias entre o fim da prescrição e o início da prescrição seguinte. Odds ratio (OR) com intervalos de confiança de 95% (IC95%) foram calculados por meio de modelos de regressão logística para estimar a chance de apresentar persistência na terapia após o primeiro e os dois primeiros anos de seguimento. RESULTADOS: Foram incluídos 11.642 pacientes com artrite reumatoide - 2.241 iniciaram uso de agentes anti-TNF (+/-MMCD) e 9.401 iniciaram MMCD - e 1.251 pacientes com espondilite anquilosante - 976 iniciaram uso de agentes anti-TNF (+/-MMCD) e 275 iniciaram MMCD. No primeiro ano de acompanhamento, 63,5% persistiram em terapia com anti-TNF (+/-MMCD) e 54,1% em uso de MMCD do grupo com artrite reumatoide. Em relação à espondilite anquilosante, 79,0% do grupo anti-TNF (+/-MMCD) e 41,1% do grupo MMCD persistiram no tratamento. O OR (IC95%) para persistência na terapia foi de 1,50 (1,34-1,67) para o grupo anti-TNF (+/-MMCD) comparado com MMCD no primeiro ano em pacientes com artrite reumatoide, e de 2,33 (1,74-3,11) em pacientes com espondilite anquilosante. Foi observada tendência semelhante ao final do segundo ano. CONCLUSÕES: Observou-se uma tendência geral de taxas mais elevadas de persistência na terapia com anti-TNF (+/-MMCD) em relação a MMCD no período estudado. Foram observadas taxas de persistência mais elevadas para os usuários de anti-TNF (+/-MMCD) em pacientes com espondilite anquilosante em relação a artrite reumatoide, e maior persistência para MMCD em pacientes com artrite reumatoide em relação à espondilite anquilosante.

[Evaluation of potential drug interactions in primary health care prescriptions in Vitória da Conquista, Bahia (Brazil)]. / Avaliação de interações medicamentosas potenciais em prescrições da atenção primária de Vitória da Conquista (BA), Brasil.

Drug interactions are risk factors for the occurrence of adverse drug reactions. The risk for drug interactions includes factors related to prescription that are intrinsic to the patient. This study sought to evaluate the potential drug interactions in primary care prescriptions in Vitória da Conquista in the state of Bahia to fill the knowledge gap on this topic in Brazil. Information about several variables derived from the primary health care prescriptions was collected and drug interactions were evaluated based on information from Medscape and Micromedex(R) databases. Polypharmacy frequency and its association with the occurrence of drug interactions were also evaluated. Results revealed a 48,9% frequency of drug interactions, 74,9% of moderate or greater severity, 8,6% of prescriptions in polypharmacy that in the chi-square test showed a positive association with the occurrence of drug interactions (p < 0,001). Prescriptions from primary care in Vitória da Conquista in the state of Bahia showed a high frequency of drug interactions, however it is necessary to analyze other risk factors for their occurrence at this level of health care.

Restrictive measure for the commercialization of antimicrobials in Brazil: results achieved / Medida restritiva para comercialização de antimicrobianos no Brasil: resultados alcançados

ABSTRACT OBJECTIVE To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006-0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003-0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

RESUMO OBJETIVO Avaliar se a incidência de infecção hospitalar por microrganismo resistente diminuiu após a implementação da medida restritiva da Agência Nacional de Vigilância Sanitária para comercialização de antimicrobianos. MÉTODOS Estudo de coorte histórica de registros de prontuários de pacientes adultos admitidos para internação em um hospital geral e público no período de maio de 2010 a julho de 2011. Foi formada uma coorte com pacientes internados em período anterior à medida restritiva para comercialização de antimicrobianos (Fase I) e uma segunda coorte com pacientes admitidos após a implantação da medida restritiva (Fase II). RESULTADOS O risco instantâneo de infecção hospitalar por microrganismo resistente foi estimado em sete por 1.000 pessoas-tempo (IC95% 0,006-0,008) na Fase I, e quatro por 1.000 pessoas-tempo (IC95% 0,003-0,005) na Fase II do estudo. As diferenças entre as curvas de sobrevida nas diferentes fases do estudo e estratificadas pela faixa etária também foram significativas (p < 0,05). CONCLUSÕES Os resultados sugerem que a implantação da medida restritiva de comercialização de antimicrobianos pela Agência Nacional de Vigilância Sanitária reduziu a incidência de infecção hospitalar por microrganismo resistente.

[Health survey in Quilombola communities (descendants of Afro-Brazilian slaves who escaped from slave plantations that existed in Brazil until abolition in 1888) in Vitória da Conquista in the state of Bahia (COMQUISTA Project), Brazil: methodological aspects and descriptive analysis]. / Inquérito de Saúde em Comunidades Quilombolas de Vitória da Conquista, Bahia, Brasil (Projeto COMQUISTA): aspectos metodológicos e análise descritiva.

The scope of this article was to present the methodology, preliminary descriptive results and the reliability of the instruments used in the COMQUISTA Project. It involved a cross-sectional study with adults (>18 years) and children (up to 5 years old) of Quilombola communities in Vitória da Conquista, Bahia. Data collection consisted of individual and household interviews, anthropometric and blood pressure measurements. A semi-structured questionnaire adapted from the Brazilian National Health Survey (PNS) was used and the interviews were conducted using handheld computers. 397 housing units were visited and 797 adults and 130 children were interviewed. The demographic profile of the Quilombolas was similar to the Brazilian population with respect to sex and age, however, they had precarious access to basic sanitation and a low socioeconomic status. The analysis of reliability revealed the adequacy of strategies adopted for quality assurance and control in the study. The methodology used was considered adequate to achieve the objectives and can be used in other populations. The results indicate the need for implementing strategies to improve the quality of life and reduce the degree of vulnerability of the Quilombolas.

[Medication use by the quilombola population: a survey in Southwestern Bahia, Brazil]. / Utilização de medicamentos pela população quilombola: inquérito no Sudoeste da Bahia.

OBJECTIVE: To characterize the medication use by the quilombola population. METHODS: A population-based cross-sectional study was conducted with 797 adult quilombola in Vitória da Conquista, BA, Northeastern Brazil, in 2011. Analysis of variance was used to compare means of drugs by subject, according to demographic, socioeconomic and health-related behavior variables. Prevalence, prevalence ratios and their 95% confidence intervals were estimated. Multivariate analysis was carried out using Poisson regression with robust variance. RESULTS: The most widely consumed drugs by the population were those for the cardiovascular and nervous systems. Prevalence of medication use was 41.9%, significantly higher among women (50.3%) than men (31.9%). After adjusted analysis, medication use was associated with being female gender, being aged 60 or older, higher economic level, worse self-rated health, greater number of self-reported diseases and number of medical appointments. CONCLUSIONS: Strategies to improve rational drug use should preferentially focus on women and older adults. Thus, special attention should be given to promote rational prescription in everyday health services.

[Hospital readmissions related to drug interactions: a retrospective study in a hospital setting]. / Interação medicamentosa associada à reinternação hospitalar: estudo retrospectivo em um hospital geral.

OBJECTIVE: To examine the relationship between potential drug interactions and hospital readmissions. METHODS: Retrospective study with 1,487 adult patients (> 18 years old) admitted to a general hospital in the city of Vitória da Conquista, Northeastern Brazil, from January to December 2007. Data were collected from Hospital Admission Authorization (AIH) forms in the Brazilian National Health System Hospital Database (SIH/SUS). Probabilistic linkage was used to combine multiple AIH forms from the same admission into a single record and to identify readmissions. Information on prescriptions was manually added to the SIH/SUS records. Logistic regression was used to quantitatively assess the impact of drug interactions on hospital readmissions. Cox regression was performed to test the impact of this variable on time to first readmission. RESULTS: A total of 99 readmissions (7% of all patients) were identified. Potential drug interactions were found in 35% of all prescriptions evaluated. Patients with potential drug interactions in a prior admission were more likely to be readmitted. The adjusted odds ratio indicated a 2.4-fold increase in odds of being readmitted; and the adjusted hazard ratio showed that this risk was increased by 79% in patients with potential drug interactions (p < 0.01). CONCLUSIONS: The study results suggest an association between prior drug interactions and increased risk of readmission. Health professionals should be aware of potential hazard of certain drug combinations and closely monitor high-risk patients such as elderly patients and those with renal impairment.