Cristiano Soares de Moura

Potential drug-drug interactions associated with prolonged stays in the intensive care unit: a retrospective cohort study.

BACKGROUND AND OBJECTIVES Drug-drug interactions (DDIs) are one cause of adverse drug events and can cause harm to hospitalized patients. Little has been done to study the relationship between potential DDIs and an increased length of stay (LOS) in the intensive care unit (ICU). The aim of this study was to determine the frequency of potential DDIs during ICU stays and to determine whether the frequency of these adverse events was associated with ICU LOS. METHODS This retrospective cohort study was conducted from January to December 2007 in the ICU of the General Hospital of Vitória da Conquista, Brazil. The study population comprised all patients aged >18 years admitted to the hospitals ICU. Demographic and prescription data were collected from medical files. All prescriptions administered during the period were examined. Potential DDIs were identified and classified according to the book Drug Interaction Facts. The median LOS was determined by the Kaplan-Meier method and Cox proportional hazards models were fitted to analyse the relationship between potential DDIs and the LOS. RESULTS The study population comprised 236 adults, 158 (67%) of them men, between the ages of 18 and 96 years, with a mean ± SD age of 50 ± 20 years. The median LOS among patients with at least one DDI was 12 days compared with 5 days among those with no DDIs (p < 0.01). Multiple Cox proportional regression analyses showed that a prolonged ICU stay was positively associated with DDIs (hazard ratio [HR] 0.54; 95% CI 0.37, 0.80; p < 0.01), where an HR <1 indicates a variable that increases the risk of prolonged stay (i.e. an adverse outcome). This association was true even after controlling for the cost of hospitalization, the number of procedures and the number of prescribed drugs. CONCLUSION In this study, DDIs were found to be associated with a longer ICU stay. Given that LOS is an important indicator of the quality of health care delivered and that DDIs are considered avoidable, specific measures are necessary to increase the recognition of DDIs. E-prescriptions and dispensing programmes associated with a DDI knowledge base can help health professionals identify hazardous drug combinations.

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 Vitoria 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.

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 Vitoria 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.

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

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.

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.

Medication persistence of DMARDs and anti‐TNF agents in a cohort of patients with rheumatoid arthritis in Brazil

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.

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.

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.

Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis

ABSTRACT 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.

THU0198 Risk of Hospitalized Serious Infection in Spondylitis Ankylosing (AS) Patients Using Nbdmard or Anti-TNF

Background Nonbiologic Disease-modifying anti-rheumatic drugs (nbDMARDs) and anti-tumor necrosis factor (anti-TNFs) have been used in AS patients who do not respond adequately to non-steroidal anti-inflammatories (NSAIDs). However, concerns exist regarding the risk of serious infections1. Objectives To assess the risk of serious infections associated with nbDMARDs or anti-TNF use in an AS cohort. Methods We assembled a cohort of potential AS patients identified from hospitalization discharge diagnoses or physician visit billing claims, using ICD-9 code 720 or ICD10 code M45. Patients were required to have two or more ICD codes and at least one anti-TNF or nbDMARD exposure between January 1, 2001 and December 31, 2011. Cohort entry was defined as the date of the first of these prescriptions and analysis was restricted to individuals who had not used anti-TNF drugs prior to cohort entry. Patients were excluded if they were not covered by the Quebec drug plan 1 year before the first prescription of nbDMARDs and/or an anti-TNF agent. We used Cox regression with the following three time-varying drug exposure categories: 1) nbDMARDs, 2) anti-TNF agents alone or in combination with nbDMARDs, and 3) neither drug. Models were adjusted for baseline patient sociodemographics, co-morbidity, prior health service use, and time-dependent use of NSAIDs, and corticosteroids. Current time-dependent corticosteroids dose was standardized according to the Defined Daily Dose (DDD) system. The outcome, first occurrence of an infection requiring hospitalization, was identified from hospitalization discharge diagnoses (primary or non-primary). Results We studied 714 AS patients; 469 (65.7%) were men, with a mean age of 50.3 (standard deviation 14.1) years at cohort entry. During this period, 57 cases of serious infections occurred, for an incidence rate of 3.07/100 PY. The median time from cohort entry to serious infection was 2.1 years. The incidence of serious infection was 4.12/100 PY in patients exposed to nbDMARDs alone, 2.44/100 PY in the anti-TNF +/- nbDMARDs group, and 2.25/100 PY in unexposed patients. Age, prior health service use, and use of corticosteroids in the previous year were associated with increased risk of infection in our multivariate analysis. The 95% confidence intervals, CIs, for the adjusted hazard ratios (HR) of infection (with the unexposed group as comparator) were wide and overlapping for both anti-TNF+/- nbDMARDs (HR=1.05; 95% CI 0.45-2.45) and nbDMARDs alone (HR=1.77; 95% CI 0.78-4.02). Conclusions We present novel findings demonstrating that the risk of serious infection in AS is 3% per year. In the current analyses, we were unable to draw definitive conclusions regarding the whether serious infections in AS are higher with anti-TNF or nbDMARDs use, versus non-use. However, older age, prior health service use, and use of corticosteroids appear to be important risk factors for serious infection in AS. References Grijalva CG et al. (2011). Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA. 306(21):2331-9. Acknowledgements Canadian Institutes for Health Research (CIHR) Disclosure of Interest None declared