[Performing pharmacoepidemiological studies using the French health insurance data warehouse (SNDS): How to translate guidelines into practice]. / Réalisation d'études pharmacoépidémiologiques à partir du système national des données de santé (SNDS) : application des recommandations dans la pratique.

The French health insurance data warehouse named SNDS is one of the largest medico-administrative in the world allowing for powerful pharmacoepidemiological studies, based on real-life data collected prospectively. In addition to the absolute necessity of a strong pharmacological rationale, recommendations have been thought to improve the quality of pharmacoepidemiological studies. These guidelines emphasize the importance of an accurate definition of the study population, outcome and exposure, especially for studies performed on medico-administrative databases. Compliance with certain guidelines, particularly those concerning the identification of a specific population or an outcome and the definition of risk periods or exposure periods, may be difficult when performing studies on the SNDS because of its structure and the nature of the data recorded. The objective of this article is to provide advice for the conduct of pharmacoepidemiological studies according to the recommendationswhen using the SNDS, given its specificities. The performing of reliable studies from this rich but complex data warehouse requires the expertise of researchers with deep knowledge both in the SNDS and in pharmacological reasoning.

Iron salt supplementation during gestation and gestational diabetes mellitus

ABSTRACT OBJETIVE To evaluate the association between the use of iron salts during the first two trimesters of gestation in non-anemic women and the development of gestational diabetes mellitus. METHODS The study used maternal data from the 2015 Pelotas Birth Cohort. All non-anemic women at the 24th week of gestation (n = 2,463) were eligible for this study. Gestational diabetes mellitus was self-reported by women. Crude and adjusted logistic regression were performed considering level of significance = 0.05. RESULTS Among the women studied, 69.7% were exposed to prophylactic iron supplementation in the first two trimesters of gestation. The prevalence of gestational diabetes mellitus among those exposed was 8.7% (95%CI: 7.4-10.1) and 9.3% (95%CI: 7.4-11.6) among those who were not exposed. Iron supplementation was not associated with increased risk of gestational diabetes mellitus in crude (OR = 0.9; 95%CI: 0,7-1,3) and adjusted analysis (OR = 1.1; 95%CI :0,8-1,6). CONCLUSIONS The results suggest that routine iron use in non-anemic pregnant women does not increase the risk of developing gestational diabetes. This evidence supports the existing national and international guidelines, in which prophylactic iron supplementation is recommended for all pregnant women as soon as they initiate antenatal care in order to prevent iron deficiency anemia.

Use of the French national health insurance information system for research in the field of mental health: Systematic review and perspectives.

PURPOSE: This systematic review registered in PROSPERO (CRD42021225296) aimed to describe the use of the French national health insurance information system, which covers the entire French population (67 million inhabitants), for research in the field of mental health. METHODS: Three electronic databases and a journal hand-search identified 15 265 articles from January 1, 2003 (year of creation of the database) to October 31, 2020. Studies of any design were eligible for inclusion provided that they (i) made use of at least one component of the French health insurance database and (ii) focused on a topic in near and far connection with the field of mental health in France. Database used, design and methods, study period, population, key findings, and type of use for medical research were described. RESULTS: A total of 152 studies were included in the review analysis. There was an increase in the number of published articles over time throughout the studied period. Studies focusing on adults (n = 139) largely outnumbered those focusing on children and adolescents (n = 11). Pharmacoepidemiological studies were by far the most frequent (n = 123), followed by methodological studies (n = 23), epidemiological studies (n = 17), and health economics studies (n = 3). The most studied psychotropic drugs were antidepressants (n = 27), anxiolytics (n = 27), and opioids (n = 25) while fewer studies focused on methylphenidate (n = 6) and on mood stabilizers (n = 5). Few studies specifically focused on psychiatric disorders, mainly depression (n = 4), suicide (n = 4), and psychotic disorders (n = 3). CONCLUSION: This systematic review highlighted a relatively poor exploitation of the Système national des données de santé database in the field of psychiatric research with regard to the great possibilities it offers, with a clear lag in certain fields such as epidemiological or health economics studies and in specific populations, in particular children and adolescents.

Aspects épidémiologiques et thérapeutiques de la maladie de Kawasaki à Libreville de 2014 à 2021

Introduction.Kawasaki disease (KD) is an acute multi-systemic vasculitis of young children and infants. It is the first cause of acquired cardiac disease in children and remains poorly described in Gabon. We therefore wanted to describe the epidemiological and therapeutic aspects of this disease in two hospitals in Libreville. Patients and methods.We conducted a retrospective, descriptive study from 2014 to 2021 at the Akanda University Hospital and the El Rapha polyclinic in Libreville. All records of patients hospitalised in paediatrics for MK were included. Results.Thirty three cases of MK were retrieved, giving ahospital prevalence of0.6%. The mean age of patients was 20.4 months, the proportion of patients <18 months was 60.6% and the sex ratio was 1.7. The symptoms were observed mainly during the dry season (69.7%). Fever (100%), conjunctivitis (78.8%) and desquamation (72.7%) were the main reasons for consultation. In 24.2% of cases, a traditional medicine was administered. The average time between the onset of symptoms and hospitalization was 11 days. Once hospitalized, the diagnosis of MK was evoked within an average of 3 days. The typical form was observed in 57.6% of cases. In 100% of cases, the hemoglobin level was <12g/dl and the CRP was >15mg/l. Echocardiography was abnormal in 5 patients. Acetylsalicylic acid was the only treatment with a mean time to apyrexia of 3 days after administration. No deaths were recorded. Conclusion:the MK is relatively present in Libreville. It is important to mention it in the event of a fever of more than 5 days.

Validity of ICD-10-CM diagnoses to identify hospitalizations for serious infections among patients treated with biologic therapies.

PURPOSE: Identifying hospitalizations for serious infections among patients dispensed biologic therapies within healthcare databases is important for post-marketing surveillance of these drugs. We determined the positive predictive value (PPV) of an ICD-10-CM-based diagnostic coding algorithm to identify hospitalization for serious infection among patients dispensed biologic therapy within the FDA's Sentinel Distributed Database. METHODS: We identified health plan members who met the following algorithm criteria: (1) hospital ICD-10-CM discharge diagnosis of serious infection between July 1, 2016 and August 31, 2018; (2) either outpatient/emergency department infection diagnosis or outpatient antimicrobial treatment within 7 days prior to hospitalization; (3) inflammatory bowel disease, psoriasis, or rheumatological diagnosis within 1 year prior to hospitalization, and (4) were dispensed outpatient biologic therapy within 90 days prior to admission. Medical records were reviewed by infectious disease clinicians to adjudicate hospitalizations for serious infection. The PPV (95% confidence interval [CI]) for confirmed events was determined after further weighting by the prevalence of the type of serious infection in the database. RESULTS: Among 223 selected health plan members who met the algorithm, 209 (93.7% [95% CI, 90.1%-96.9%]) were confirmed to have a hospitalization for serious infection. After weighting by the prevalence of the type of serious infection, the PPV of the ICD-10-CM algorithm identifying a hospitalization for serious infection was 80.2% (95% CI, 75.3%-84.7%). CONCLUSIONS: The ICD-10-CM-based algorithm for hospitalization for serious infection among patients dispensed biologic therapies within the Sentinel Distributed Database had 80% PPV for confirmed events and could be considered for use within pharmacoepidemiologic studies.

Prevalence and factors associated with the consumption of folic acid and iron in pregnant women in the BRISA cohort / Prevalência e fatores associados ao uso de ácido fólico e ferro em gestantes da coorte BRISA

Abstract Objectives: to describe the prevalence and factors associated with the consumption of folic acid and iron among puerperal women in the city of São Luís, Maranhão. Methods: a cross-sectional study with 4,036 puerperal women through a standardized questionnaire. The dependent variables (outcomes) were: the consumption of folic acid during pregnancy, iron and folic acid before pregnancy. The independent variables: age; schooling; skin color; marital status; income; planned pregnancy; place and number of prenatal consultations. Statistical analyzes were performed on STATA 14.0. For the first two outcomes, Poisson model with a robust variance was used. And for the last one, logistic regression. Results: the prevalence of consuming folic acid and iron during pregnancy were, respec-tively, 77.27% and 84.98%. However, only 0.37% reported the consume of folic acid and iron before pregnancy. In the adjusted analysis, the variables associated with the consumption of folic acid during pregnancy were: schooling and income; the consume of iron during preg-nancy, age only; and for those who consumed folic acid before pregnancy, no variable was statistically significant. Conclusions: high percentage of puerperal women who consumed folic acid and iron supplements during pregnancy, however, the recommended consumption of folic acid before pregnancy was low and maternal, social and economic factors influence the consumption of these supplements.

Resumo Objetivos: descrever prevalência e fatores associados ao uso deácido fólico e ferro entre puérperas do município de São Luís, Maranhão. Métodos: estudo transversal com 4.036 puérperas através de questionário padronizado. As variáveis dependentes (desfechos) foram: uso durante a gestação de ácido fólico, ferro e ácido fólico antes da gestação. As variáveis independentes: idade; escolaridade; cor da pele; situação conjugal; renda; gravidez planejada; local e número de consultas do pré-natal. As análises estatísticas foram realizadas no STATA 14.0. Para os dois primeiros desfechos, utilizou-se modelo de Poisson com variância robusta. Para o último, regressão logística. Resultados: a prevalência do uso de ácido fólico e ferro durante a gestação foram, respectivamente, 77,27% e 84,98%. Entretanto, apenas 0,37% declararam uso antes da gestação. Na análise ajustada, as variáveis associadas com uso de ácido fólico durante a gestação foram: escolaridadee renda; parausode ferro durante a gestação, apenas a idade; e para as que fizeram uso de ácido fólico antes da gestação, nenhuma variável mostrou-se estatisticamente significativa. Conclusões: alto percentual de puérperas fez uso de suplementos de ácido fólico e ferro-durante a gestação, porém o uso recomendado de ácido fólico antes da gestação mostrou-se baixo e que fatores maternos, sociais e econômicos influenciam no consumo destes suple-mentos.

Tuberculosis drug safety and pharmacovigilance in health system of Kosova: A cross-sectional analysis.

BACKGROUND: Tuberculosis (TB) remains a significant worldwide social and life-threatening epidemiological problem. Because this disease requires multiple drug treatment and prolonged therapy for several months, followed by a high probability of adverse effects (AEs), we assessed AE monitoring for anti-TB drugs in the Health Care System of Kosova. METHODS: This survey was a cross-sectional analysis performed at the primary, secondary and tertiary health care levels in Kosova. We included 930 registered tuberculosis patients within three levels of this health system in our study. Furthermore, we interviewed 62 physicians and 71 nurses at TB health facilities. Data were collected from official TB registers and personal contact with patients for 12 months. RESULTS: The representative age group was 19 to 29 years (30.49%), followed by a group of patients aged >60 years (23.23%). Among 930 patients treated with TB drugs, the total incidence of adverse AEs was 29.03%. Female TB patients had a higher rate of AEs than did male patients (33.56% vs 28.84%, respectively). The highest incidence of registered AEs was recorded in the gastrointestinal system (270, 80.83%), followed by the central nervous system (CNS, 7.50%) and was lower in other organ systems. The reporting of anti-TB drug effects by medical staff (TB medical doctor and TB medical nurse) at different levels of TB medical settings occurred among 62.90% of medical doctors and 81.69% of nurses. Only 53.23% of medical doctors and 46.48% of nurses completed pharmacovigilance training. CONCLUSION: The pharmacovigilance approach in Health System of Kosova is not comprehensible and not systematic. The relatively low incidence of AEs among TB patients is due under reporting of these by medical staff. The knowledge, attitudes, and adherence of medical staff reveal low awareness for pharmacovigilance activities, and this concern should be addressed to reinforce this important issue for the safe treatment of TB patients.

Screening to identify signals of opioid drug interactions leading to unintentional traumatic injury.

BACKGROUND: Efforts to minimize harms from opioid drug interactions may be hampered by limited evidence on which drugs, when taken concomitantly with opioids, result in adverse clinical outcomes. OBJECTIVE: To identify signals of opioid drug interactions by identifying concomitant medications (precipitant drugs) taken with individual opioids (object drugs) that are associated with unintentional traumatic injury DESIGN: We conducted pharmacoepidemiologic screening of Optum Clinformatics Data Mart, identifying drug interaction signals by performing confounder-adjusted self-controlled case series studies for opioid + precipitant pairs and injury. SETTING: Beneficiaries of a major United States-based commercial health insurer during 2000-2015 PATIENTS: Persons aged 16-90 years co-dispensed an opioid and ≥1 precipitant drug(s), with an unintentional traumatic injury event during opioid therapy, as dictated by the case-only design EXPOSURE: Precipitant-exposed (vs. precipitant-unexposed) person-days during opioid therapy. OUTCOME: Emergency department or inpatient International Classification of Diseases discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to generate confounder adjusted rate ratios. We accounted for multiple estimation via semi-Bayes shrinkage. RESULTS: We identified 25,019, 12,650, and 10,826 new users of hydrocodone, tramadol, and oxycodone who experienced an unintentional traumatic injury. Among 464, 376, and 389 hydrocodone-, tramadol-, and oxycodone-precipitant pairs examined, 20, 17, and 16 (i.e., 53 pairs, 34 unique precipitants) were positively associated with unintentional traumatic injury and deemed potential drug interaction signals. Adjusted rate ratios ranged from 1.23 (95 % confidence interval: 1.05-1.44) for hydrocodone + amoxicillin-clavulanate to 4.21 (1.88-9.42) for oxycodone + telmisartan. Twenty (37.7 %) of 53 signals are currently reported in a major drug interaction knowledgebase. LIMITATIONS: Potential for reverse causation, confounding by indication, and chance CONCLUSIONS: We identified previously undescribed and/or unappreciated signals of opioid drug interactions associated with unintentional traumatic injury. Subsequent etiologic studies should confirm (or refute) and elucidate these potential drug interactions.

Vitamin, micronutrients and supplement prescribing patterns in a group of ambulatory colombian patients, 2016 / Patrones de prescripción de vitaminas y suplementos nutricionales en un grupo de pacientes de Colombia

Abstract Introduction: Vitamins and micronutrients are essential organic substances in the metabolic processes of living things, and supplementation is only recommended in conditions of nutritional deficits. Objective: To determine the prescription patterns of vitamins and supplements in a group of patients enrolled in the Colombian Health System in 2016. Methodology: This was a cross-sectional study based on a population database. Vitamin-prescribed patients of both sexes and all ages were selected for 3 consecutive months. A database was designed using the dispensing records. SPSS 23.0 was used for the univariate, bivariate and multivariate analyses. A p-value <0.05 was considered statistically significant. Results: In total, 9998 patients receiving vitamin supplementation were identified. A female predominance was observed (n=8341, 83.4%). The mean age was 57.7±18.7 years. The most commonly formulated vitamins and micronutrients were vitamin D (58.0%), calcium (55.0%) and folic acid (25.0%). Overall, 60.8% of patients were prescribed more than one vitamin. The most frequent multiple-nutrient association was between calcium and vitamin D (n=5505); 77.3% received concurrent treatment with other medications to manage comorbidities. The probability of comedication in the multivariate analysis was higher for folic acid (OR:3.10, 95%CI 2.69-3.59), thiamine (OR:2.75, 95%CI:2.15-3.5) and calcium + vitamin D (OR:1.61, 95%CI: 1.42-1.82) and for those individuals older than 65 years (OR:1.24, 95%CI:1.02-1.51). Conclusions: Vitamins are widely used in the Colombian population. The results of this study elucidate the patterns of use of these supplements and offer proposed strategies to the future and to evaluate and minimize prescriptions that are potentially inappropriate or of little therapeutic value. MÉD.UIS. 2020;33(2):41-8.

Resumen Introducción: Las vitaminas y micronutrientes son sustancias orgánicas esenciales en los procesos metabólicos de los seres vivos y solo se recomienda suplementación en condiciones con déficits nutricionales. Objetivo: Determinar los patrones de prescripción de vitaminas y suplementos en un grupo de pacientes afiliados al Sistema de Salud en Colombia, en el año 2016. Métodos: Estudio de corte transversal a partir de una base de datos poblacional. Se seleccionaron pacientes con prescripción de vitaminas por 3 meses consecutivos de ambos sexos y todas las edades. Se diseñó una base de datos con los registros de dispensación. Se usó SPSS 23.0 para análisis univariados, bivariados y multivariados. Se consideró estadísticamente significativo un valor de p<0,05. Resultados: Se hallaron 9998 pacientes con prescripción de suplementos vitamínicos. Se halló un predominio femenino (n=8341; 83,4%). La edad media fue de 57,7±18,7 años, las vitaminas y micronutrientes más formulados fueron: vitamina D (58,0%), calcio (55,0%) y ácido fólico (25,0%). El 60,8% de pacientes tenía más de un suplemento prescrito. La asociación más frecuente fue calcio y vitamina D (n=5505), y el 77,3% recibía tratamiento simultáneo con otros medicamentos para el control de comorbilidades. La probabilidad de comedicacion en el análisis multivariado fue mayor en formulados con ácido fólico (OR:3,10; IC95%:2,69-3,59), tiamina (OR:2,75; IC95%:2,15-3,50), calcio+vitamina D (OR:1,61; IC95%:1,42-1,82) y los mayores de 65 años (OR:1,24; IC95%:1,02-1,51). Conclusiones: Las vitaminas son ampliamente usadas en la población colombiana, los hallazgos de este estudio permiten conocer un estado de los patrones de uso de estos suplementos, así como plantear estrategias para racionalizar las prescripciones potencialmente inapropiadas o de poco valor terapéutico. MÉD.UIS. 2020;33(2):41-8.

[PRACTICE OF MANAGEMENT OF PATIENTS WITH INFECTIOUS ENDOCARDITIS IN CONDITIONS OF LOW FREQUENCY OF ETIOLOGICALLY SIGNIFICANT PATHOGENS IN THE RUSSIAN FEDERATION].

The article presents the results of a multicenter study of the etiology, antibiotic sensitivity and pharmacoepidemiology of infective endocarditis in the Russian Federation. The purpose of this study is to analyze the current practice of management of patients with infective endocarditis in conditions of low frequency of etiologically significant pathogens in the Russian Federation. The study included patients of both sexes of all age groups with definite and probable infective endocarditis. 406 cases of infectious endocarditis (240 in retrospect and 166 in the prospective part) were analyzed. Etiologically significant pathogen was isolated in 144 cases (35.5%). The structure of pathogens was dominated by gram (+) cocci (90.3%), most often - Staphylococcus aureus (46.5% of all isolated pathogens). Aminoglycosides (22.8%), parenteral cephalosporins of the III generation (22.1%) and glycopeptides (14.5%) were most frequently used in the course of starting antimicrobial therapy. When changing the mode of antimicrobial therapy, glycopeptides (18.6%), aminoglycosides (15.3%), fluoroquinolones (11.2%) and parenteral cephalosporins of generation III (9.5%) were most often prescribed.

Medication Use among Pregnant Women from the 2015 Pelotas (Brazil) Birth Cohort Study.

Background: Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women from the 2015 Pelotas (Brazil) Birth Cohort Study. Methods: This paper relies on a population-based cohort study including 4270 women. Participants completed a questionnaire about the antenatal period, including information about medication use. We performed descriptive analyses of the sample and the medications used and adjusted analyses for the use of medications and self-medication. Results: The prevalence of medication use was 92.5% (95% CI 91.7-93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3-29.1). In the adjusted analysis, women who had three or more health problems during pregnancy demonstrated higher use of medicines. Self-medication was higher in lower income groups and among smokers and multiparous women (three pregnancies or more). Acetaminophen, scopolamine, and dimenhydrinate were the medications most commonly used. Conclusions: This study describes the pattern of drug use among pregnant women in a population-based cohort study, with a high prevalence of self-medication. Greater awareness of the risks of self-medication during pregnancy is required, focusing on groups more prone to this practice, as well as ensuring qualified multidisciplinary prenatal care.

An algorithm to identify pregnancies in BIFAP Primary Care database in Spain: Results from a cohort of 155 419 pregnancies.

PURPOSE: There has been a notable progress on the development of methods for identification of pregnancies using primary care databases. We aimed to evaluate the prescription of medications during pregnancy applying a novel algorithm. METHODS: We identified pregnancies in women aged 15 to 49 years registered in the Database for Pharmacoepidemiological Research in Primary Care (BIFAP) between 2002 and 2015. The algorithm applied sequential cycles that searched in hierarchical order for indicators of conception, delivery or pregnancy loss, and other codes suggestive of pregnancy. Length of pregnancy was assessed by searching for last menstrual period (LMP) date, gestational age, and outcomes of pregnancy. Prescription of specific drugs during the pre-pregnancy period and first trimester and time trends during pregnancy were evaluated. RESULTS: We identified a total of 155 419 pregnancies during the study period (77.5% completed pregnancies, 21.5% pregnancies losses, 0.8% ectopic pregnancies, and 0.2% stillbirths). Excluding vitamins and supplements, 43.8% of women received at least one prescription during the pre-pregnancy period and 68.4% during the first trimester. During the first trimester, the most commonly drugs prescribed were analgesics (16.3%) followed by antibiotics (11.8%). From 2002/2003 to 2014/2015, there was an increase of prescriptions for thyroid hormones (1.0% vs 4.7%), H2 blockers (1.0% vs 2.2%), and PPIs (1.4% vs 2.2%). While antidepressants (2.0% vs 1.5%) and benzodiazepines (3.1% vs 2.4%) decreased in the last period. CONCLUSION: Having in mind the challenges of identifying pregnancies in health care databases, this study demonstrates the usefulness of BIFAP database for studies on drug utilization during pregnancy.

Development and preliminary validation of an instrument to enable laypersons to assess suspected side effects from medicines.

PURPOSE: Research into causality assessment tools enabling patients to assess suspected adverse drug reactions (ADRs) is limited. Supporting patients with tools could improve their confidence in discussions with health professionals and encourage reporting of suspected ADRs to regulators. This study describes development and preliminary validation of an instrument: Side Effect Patient ASsessment Tool (SE-PAST). METHODS: SE-PAST was developed from survey and interview data involving patients experiencing suspected ADRs. It included 10 statements enabling causality assessment, covering timing, additional information sources, and experiences, with four options: yes/no/don't know/not applicable. Scoring and weighting resulted in four categories of causal association: highly probable, probable, possible, unlikely. Validation involved obtaining feedback from 31 individuals experiencing an ADR. Further validation involved online distribution through patient support groups and comparison of reported symptoms to known ADRs. RESULTS: Validators found SE-PAST easy to read (31), to understand (27), and to complete (29). A total of 294 respondents completed SE-PAST online, with 98% completing eight or more causality assessment statements. Symptoms were categorised as highly probable (46; 16%), probable (80; 62%), possible (44; 15%), and unlikely (21; 7%). A total of 221 respondents identified one suspected medicine, with 95% of these reporting at least one symptom known to be an ADR. Of 227 providing feedback, 139 (61%) found SE-PAST useful, 160 (71%) felt motivated to discuss their experience with a health professional, and 136 (60%) were encouraged to report to the regulator. CONCLUSION: SE-PAST was easily completed and understood by people experiencing suspected ADRs and could be useful in encouraging patient reporting to health professionals and agencies.

Safety profile of traditional Chinese herbal injection: An analysis of a spontaneous reporting system in China.

PURPOSE: Although a series of serious adverse events have continually raised concerns about the potential toxicity of traditional Chinese medicine injections (TCM injections), studies on this subject are still sparse. We conducted a descriptive analysis of a spontaneous reporting system in China to describe the safety profile of TCM injections. METHODS: The safety profile of TCM injections is described by descriptive analysis of 559 066 adverse reports collected from Guangdong Provincial Center for adverse drug reaction (ADR) Monitoring in China during 2003 to 2017. RESULTS: The percentage of new or serious ADRs of TCM injections is much higher than average percentage of China's spontaneous reporting system (SRS) as a whole (48.70% vs <25%). Compared with conventional injections, TCM injections have a slightly lower percentage of serious ADRs (6.02% vs 6.72%) and much higher percentage of unknown (new) ADRs (46.74% vs 24.13%). The gender and age distribution for TCM injections are similar to conventional injections. The reporting rates of ADRs increased with age. Anaphylactic shock and anaphylactoid reaction are high-risk ADRs for TCM injections and, anaphylactic shock is ranked number 1 in causing deaths (50.00%). CONCLUSIONS: There are some differences and similarities on the safety profile between TCM injections and conventional injections. TCM injections have higher risk of adverse effects than any other dosage forms of TCM medications and higher percentage of new or serious adverse effects than conventional injections. A lot of work need to be done to clarify the huge amount of potential unknown adverse effects related to TCM injections.

The value of a health insurance database to conduct pharmacoepidemiological studies in oncology.

Some concerns have emerged about the evidence of benefits on survival outcomes or quality of life of new anticancer drugs. In parallel, the decreased cancer mortality leads to an increased number of patients exposed to cancer treatment-related consequences. In this context, pharmacoepidemiology is crucial to assess anticancer drug use, effectiveness and safety in real life conditions. We aimed to describe strengths, limitations and considerations associated with the use of the French national health insurance database (système national des données de santé [SNDS]) to conduct pharmacoepidemiological studies in oncology. The SNDS represents a powerful tool in pharmacoepidemiology owing to its extensive coverage, accurate description and quantification of drug exposure and individual data on patients. The main limitations of this database ensue from the administrative nature resulting in technical difficulties in its management and gaps in availability of data. Another limitation is the lack of accurate identification of diseases, comorbidities or outcomes and potential confounding with notably the lack of data regarding cancer stage, prognosis or risk factors. Finally, the accurate identification of the nature of chemotherapy received by patients is sometimes complex. To minimize these limitations, several approaches and statistical methods could be used as highlighted by national or international initiatives. First, the SNDS may be linked with cancer registry or clinical data. Then, several data sources could be combined using meta-analytical methods. The development of methodological tools and the use of standardized methods are crucial to enhance the quality of studies that can impact clinical practice and guide public decision. Pharmacoepidemiological approaches and pharmacovigilance represent an important cornerstone in oncology for signal detection or long-term follow up of cancer patients. In this context, validated methods to identify cancer patients and to describe chemotherapy regimens within these data should be promoted and remain too scarce despite international guidelines. Moreover, limits and strength of each data sources should be systematically discussed according to the research question. Optimized and framed use of claims database represents a future challenge in onco-pharmacoepidemiology.

Medication history assessment in research: A randomized controlled trial comparing tablet-based (eMedHAT) versus structured interview (MedHAT).

PURPOSE: Accurate capture of medication use is important for high quality research. For epidemiologic studies, medication histories are the most common measure of exposure when trying to identify associations between medications and outcomes. Concomitant medications can alter the efficacy or safety of study drugs in clinical trials. However, there are few studies evaluating the accuracy and efficiency of methods to collect these histories. The objective of this study is to compare the accuracy of medication histories collected by structured interview to histories captured using a tablet-based application. METHODS: This was a randomized controlled trial. Subjects were instructed to record all prescription medications, non-prescription medications, vitamins, and dietary supplements in a diary for 30 days. At the end of the diary collection, subjects were randomized to providing a medication history during a structured interview by a trained research assistant (MedHAT) or using a tablet-based application (eMedHAT). The accuracy of these histories was compared using an adjusted analysis. We also measured the duration of the history collection and data entry. RESULTS: A total of 111 subjects were in the MedHAT group and 109 subjects were in the eMedHAT group. Recall of medications for the 30-day period was similar for MedHAT and eMedHAT (76.9% versus 75.2%, respectively). The total time required for researchers and subjects for history collection and data entry was 16 minutes shorter for the tablet-based method. CONCLUSIONS: Tablet-based medication histories were as accurate as histories obtained by research assistants and required less time for the researcher.

Xafran, a drug utilization study of rivaroxaban in stroke prevention in atrial fibrillation in France using a claim database.

BACKGROUND: Little is known about the utilization of rivaroxaban in real life treatment settings in France. AIMS: Objectives of this study were to describe the conditions of use and treatment persistence in patients with atrial fibrillation and treated with rivaroxaban for stroke prevention (SP-AF). METHODS: A cohort study was performed using a representative sample of the French nationwide database. All adults who initiated rivaroxaban for SP-AF between 01/08/2012 and 31/12/2014 were included and followed for one year. Inappropriate use of rivaroxaban's was defined as use inconsistent with the summary of product characteristics. RESULTS: In this study, 1278 patients were included, 687 (53.8%) were men and the mean age was 73.4years; 123 patients (9.6%) had a stroke and 78 (6.1%) a major bleeding event in the three years before rivaroxaban initiation. At treatment initiation 236 (18.5%) had chronic congestive heart failure, 991 (77.5%) hypertension, 247 (19.3%) diabetes and 9 (0.7%) HIV, hepatitis B or C infection. No anticoagulant had been administered in the six previous months for 777 patients (60.8%); 160 patients (12.5%) had an inappropriate use of rivaroxaban in SP-AF. At 6 and 12 months after the first delivery with rivaroxaban, 62.8%, and 51.7% (68.5% and 60.5% in sensitivity analyses) of the patients were still treated with rivaroxaban. The proportion of patients with a continuous medication availability above 80% was 96.1%. CONCLUSION: The characteristics of patients in this study are similar to patients treated with this drug in other observational studies. Adherence and persistence with rivaroxaban can be considered good.

Analysis of Drug-Drug Interactions in Swiss Claims Data Using Tizanidine and Ciprofloxacin as a Prototypical Contraindicated Combination.

BACKGROUND: Potential drug-drug interactions (pDDIs) are described in various case reports, but few studies have evaluated the impact of specific combinations on a population level. OBJECTIVE: To analyze the type and frequency of multiple contraindicated (X-pDDIs) and major interactions (D-pDDIs) and to subsequently assess the impact of the particular combination of tizanidine and ciprofloxacin on outpatient physician visits and hospitalizations. METHODS: Anonymized Swiss claims data from 524 797 patients in 2014-2015 were analyzed. First, frequencies of X- and D-pDDIs were calculated. Next, a retrospective cohort study was conducted among patients prescribed tizanidine and ciprofloxacin (exposed, n = 199) or tizanidine and other antibiotics (unexposed, n = 960). Hospitalizations and outpatient physician visits within 7, 14, and 30 days after initiation of antibiotic therapy were evaluated using multiple binary logistic regression and multiple linear regression. RESULTS: The relative frequencies of X- and D-pDDIs were 0.4% and 6.65%, respectively. In the cohort study, significant associations between exposure to tizanidine and ciprofloxacin and outpatient physician visits were identified for 14 and 30 days (odds ratio [OR] = 1.61 [95% CI = 1.17-2.24], P = 0.004, and OR = 1.59 [95% CI = 1.1-2.34], P = 0.016). A trend for increased risk of hospitalization was found for all evaluated time periods (OR = 1.68 [95% CI = 0.84-3.17], OR = 1.52 [95% CI = 0.63-3.33], and OR = 2.19 [95% CI = 0.88-5.02]). Conclusion and Relevance: The interaction between tizanidine and ciprofloxacin is not only relevant for individual patients, but also at the population level. Further investigation of the impact of other clinically relevant DDIs is necessary to improve patient safety and reduce avoidable health care utilization.

Time to and factors associated with initiation of biological therapy in patients with rheumatoid arthritis in Colombia / Tiempo y factores asociados con el inicio de terapia biológica con antirreumáticos modificadores de enfermedad en pacientes con Artritis Reumatoide en Colombia

ABSTRACT Aims: To determine the time Colombian patients with rheumatoid arthritis (RA) are treated with non-biological disease-modifying antirheumatic drugs (DMARDs) before changing to biological therapy. Methods: A retrospective cohort study that collected information about the start of antirheumatic treatment in patients of all ages with a diagnosis of RA until the change to biological DMARD therapy. Survival analysis using Kaplan-Meier curves, from 1 January 2007 until 31 December 2013 by SPSS 23.0 for Windows, was made. Results: A total of 3880 patients (75.3% women) with a mean age of 51.3 years started non-biological DMARDs. After 5 years, 234 patients (6.0%) initiated biological DMARD therapy in 17.5 ± 13.9 months. The use of glucocorticoids (OR: 2.49; 95% CI: 1.658-3.732), having any comedication (OR: 1.83; 95%CI: 1.135-2.966) and being treated in the city of Bogota (OR: 2.30; 95%CI: 1.585-3.355) or in the cities of the Colombian Atlantic coast (OR: 2.848; 95%CI: 1.468-5.524) were associated with a higher likelihood of biological DMARD initiation. Whereas the initiation of therapy with methotrexate (OR: 0.04; 95% CI: 0.014-0.108; p < 0.001) or chloroquine (OR: 0.13; 95% CI: 0.092-0.187; p < 0.001) or receiving antihypertensive medication (OR: 0.64; 95% CI: 0.421-0.960; p = 0.031) was associated with a significant reduce in likelihood. Conclusion: After 5 years of non-biological DMARD therapy, 6.0% of people with RA started biological DMARDs. Receiving glucocorticoids, having any comedication, being treated in Bogota City or cities of the Colombian Atlantic coast affected the probability of switching to biological therapy in these patients.

RESUMEN Objetivo: Determinar el tiempo transcurrido desde que pacientes de Colombia con artritis reumatoide (AR) en tratamiento con fármacos antirreumáticos modificadores de enfermedad no biológicos (FAMEs) cambian a terapia con biológicos. Materiales y métodos: Estudio de cohorte retrospectiva que recogió información sobre inicio de tratamiento antirreumático en pacientes de todas las edades con diagnóstico de AR hasta que pasaron a terapia con FAMEs biológicos. Se hizo un análisis de sobrevida, utilizando curvas de Kaplan-Meier, desde el 1 de enero de 2007 hasta el 31 de diciembre de 2013 mediante SPSS 23.0 para Windows. Resultados: Un total de 3880 pacientes iniciaron terapia con FAMEs no biológicos, (75,3% fueron mujeres) con una edad media de 51,3 anos. Tras cinco años de seguimiento, 234 pacientes (6,0%) iniciaron FAMEs biológicos en promedio a los 17,5 ± 13,9 meses. El uso de corticoides (OR: 2,49; IC95%: 1,658-3,732; p<0,001), recibir alguna comedicación (OR: 1,83; IC95%: 1,135-2,966), ser tratado en Bogotá (OR: 2,30; IC95%: 1,585-3,355), en las ciudades de la costa Atlántica (OR: 2,848; IC95%: 1,468-5,524) estuvieron asociados con una mayor probabilidad de inicio de biológicos mientras que el uso de metotrexate (OR: 0,04; IC95%: 0,014-0,108) o cloroquina (OR: 0,13; IC95%: 0,092-0,187) o recibir medicación antihipertensiva (OR: 0,64; IC95%: 0,421-0,960) redujeron la posibilidad. Conclusiones: Después de cinco años de terapia antirreumática convencional, un 6,0% de pacientes con AR inició terapia con FAMEs biológicos. Recibir corticoides, recibir comedicación, ser tratado en Bogotá o la costa Atlántica afectan la probabilidad de cambiar a terapia biológica.

Use of text-mining methods to improve efficiency in the calculation of drug exposure to support pharmacoepidemiology studies.

Background: Efficient generation of structured dose instructions that enable researchers to calculate drug exposure is central to pharmacoepidemiology studies. Our aim was to design and test an algorithm to codify dose instructions, applied to the NHS Scotland Prescribing Information System (PIS) that records about 100 million prescriptions per annum. Methods: A natural language processing (NLP) algorithm was developed that enabled free-text dose instructions to be represented by three attributes - quantity, frequency and qualifier - specified by three, three and two variables, respectively. A sample of 15 593 distinct dose instructions was used to test, validate and refine the algorithm. The final algorithm used a zero-assumption approach and was then applied to the full dataset. Results: The initial algorithm generated structured output for 13 152 (84.34%) of the 15 593 sample dose instructions, and reviewers identified 767 (5.83%) incorrect translations, giving an accuracy of 94.17%. Following subsequent refinement of the algorithm rules, application to the full dataset of 458 227 687 prescriptions (99.67% had dose instructions represented by 4 964 083 distinct instructions) generated a structured output for 92.3% of dose instruction texts. This varied by therapeutic area (from 86.7% for the central nervous system to 96.8% for the cardiovascular system). Conclusions: We created an NLP algorithm, operational at scale, to produce structured output that gives data users maximum flexibility to formulate, test and apply their own assumptions according to the medicines under investigation. Text mining approaches can provide a solution to the safe and efficient management and provisioning of large volumes of data generated through our health systems.