Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

INTRODUCTION: Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. METHODS: The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. RESULTS: As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381 g to 4762 g, with a mean of 3439.91 g. Twenty-five infants were born at ≥37 weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n = 6 events), ear infection (n = 5 events), neonatal dyspnea (n = 3 events), and respiratory syncytial virus infection (n = 3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. CONCLUSION: A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.

Fitness of real-world data for clinical trial data collection: Results and lessons from a HARMONY Outcomes ancillary study.

BACKGROUND: Despite the extensive use of real-world data for retrospective, observational clinical research, our understanding of how real-world data might increase the efficiency of data collection in patient-level randomized clinical trials is largely unknown. The structure of real-world data is inherently heterogeneous, with each source electronic health record and claims database different from the next. Their fitness-for-use as data sources for multisite trials in the United States has not been established. METHODS: For a subset of participants in the HARMONY Outcomes Trial, we obtained electronic health record data from recruiting sites or Medicare claims data from the Centers for Medicare & Medicaid Services. For baseline characteristics and follow-up events, we assessed the level of agreement between these real-world data and data documented in the trial database. RESULTS: Real-world data-derived demographic information tended to agree with trial-reported demographic information, although real-world data were less accurate in identifying medical history. The ability of real-world data to identify baseline medication usage differed by real-world data source, with claims data demonstrating substantially better performance than electronic health record data. The limited number of lab results in the collected electronic health record data matched closely with values in the trial database. There were not enough follow-up events in the ancillary study population to draw meaningful conclusions about the performance of real-world data for identification of events. Based on the conduct of this ancillary study, the challenges and opportunities of using real-world data within clinical trials are discussed. CONCLUSION: Based on a subset of participants from the HARMONY Outcomes Trial, our results suggest that electronic health record or claims data, as currently available, are unlikely to be a complete substitute for trial data collection of medical history or baseline lab results, but that Medicare claims were able to identify most medications. The limited size of the study population prevents us from drawing strong conclusions based on these results, and other studies are clearly needed to confirm or refute these findings.

Development and evaluation of standardized pregnancy identification and trimester distribution algorithms in U.S. IBM MarketScan® Commercial and Medicaid data.

OBJECTIVES: Creation of new algorithms to identify pregnancies in automated health care claims databases is of public health importance, as it allows us to learn more about medication use and safety in a vulnerable population. Previous algorithms were largely created using international classification of disease codes, but despite the U.S. code transition in 2015, few algorithms are available with the latest ICD-10-CM codes. METHODS: Using U.S. IBM MarketScan® Commercial Claims and Encounters and Multi-State Medicaid databases for women aged 10-64 years during 2014 and 2016, two pregnancy algorithms (ICD-9-CM and ICD-10-CM) were created using expert clinical review. The algorithms were evaluated by assessing the distribution of pregnancy outcomes (live birth and pregnancy losses) within each time-based cohort and the ability of the algorithms to identify select medication use during pregnancy. Medication exposure, demographics, comorbidities, and pregnancy outcomes were compared to published literature estimates for the two time periods. RESULTS: For the IBM MarketScan® Commercial database, the algorithms identified 687,228 pregnancies in 2014 and 444,293 in 2016. In the IBM MarketScan® Medicaid database, 389,132 pregnancies in 2014 and 406,418 in 2016 were identified. Percentages of most pregnancy outcomes identified using the algorithms were similar to national data sources; however, percentages of preterm births and pregnancy losses were not comparable. Most medication use estimates from the algorithms were similar to or higher than published estimates. CONCLUSIONS: By incorporating the latest ICD-10-CM codes, the new algorithms provide more complete estimates of medication use during pregnancy than algorithms using the outdated codes.

The safety of asthma medications during pregnancy and lactation: Clinical management and research priorities.

Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.

A model for human and animal data integration: Weight of evidence strategy.

BACKGROUND: Integration of animal and human data to assess potential risks of the use of medications in pregnancy is important. A qualitative weight of evidence process enables all available evidence to be considered in a consistent, systematic manner. METHODS: We aim to describe the weight of evidence methodology utilized by the authors, a summary of which was presented at the 59th Annual Meeting of the Teratology Society entitled "Integration of Human and Animal Data to Inform Medication Use in Pregnant Women." The qualitative weight of evidence process evaluates data that inform on a potential relationship between an adverse pregnancy outcome and a medication exposure. An interdisciplinary panel evaluates all available human and animal data related to the question of interest. Study quality assessments of both human and animal data are incorporated. The evaluation assesses gaps in the data from the following areas: (a) strength, (b) specificity, (c) consistency, (d) dose response relationship, (e) methodological considerations, and (f) biological plausibility for the potential association of interest. RESULTS: The panel integrates all the information to arrive at an assessment of the evidence and provides recommendations, which may include obtaining more specific information. We provide examples of how the authors apply this process at a pharmaceutical company for evaluation of potential postmarketing safety issues regarding medications and pregnancy outcomes. CONCLUSIONS: This weight of evidence method improves the ability to integrate published literature and other data sources to assess the potential risks of medication use in pregnant women and inform future drug safety studies.

Perinatal Outcomes Associated with Maternal Asthma and Its Severity and Control During Pregnancy.

BACKGROUND: Estimates of the effects of maternal asthma on pregnancy outcomes are inconsistent across studies, possibly because of differences in exposure definition. OBJECTIVE: To evaluate the risk of adverse perinatal outcomes associated with maternal asthma diagnosis, severity, and control in a large, nationally representative cohort. METHODS: This study was conducted within the IBM Health MarketScan Commercial Claims and Encounters Database (2011-2015) and the Medicaid Analytic eXtract database (2000-2014). Asthma was identified by diagnosis and treatment codes, severity was based on medications dispensed, and control was based on short-acting ß-agonist dispensations and exacerbations. We estimated the relative risks (RRs) of stillbirth, spontaneous abortion, preterm birth, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, and congenital malformations, comparing pregnancies with differing asthma disease status. RESULTS: We identified 29,882 pregnancies complicated by asthma in the MarketScan database and 160,638 in the Medicaid Analytic eXtract database. We observed no consistent associations between asthma diagnosis, severity, or control, and stillbirth, abortions, or malformations. However, we observed increased risks of prematurity, SGA, and NICU admission among women with asthma compared with those without asthma. Compared with women with well-controlled asthma, women with poor control late in pregnancy had an increased risk of preterm birth (relative risk, 1.39; 95% CI, 1.32-1.46) and NICU admission (relative risk, 1.26; 95% CI, 1.17-1.35). More severe asthma was associated with SGA (relative risk, 1.18; 95% CI, 1.07-1.30). CONCLUSIONS: We did not observe an increased risk of pregnancy losses or malformations among women with asthma. However, we found an association between asthma severity and SGA, and between exacerbations late in pregnancy and preterm delivery and NICU admission.

Poorly Controlled Asthma During Pregnancy Remains Common in the United States.

BACKGROUND: Asthma is among the most common preexisting medical conditions in pregnancy. Uncontrolled asthma may increase the risk of adverse pregnancy outcomes. OBJECTIVES: To describe the prevalence, severity, and control of asthma during pregnancy in the United States. METHODS: We identified 2 cohorts of pregnancies ending in a live birth within 2 large US health care claims databases: the Truven Health MarketScan Commercial Claims and Encounters Database (MarketScan, private insurance) for the period 2011 to 2015 and the nationwide Medicaid Analytic eXtract (MAX, public insurance) for the period 2000 to 2013. We defined asthma prevalence, severity, and control on the basis of International Classification of Diseases, 9th Revision diagnoses and asthma-related treatments. Severe asthma was defined as dispensing of 1 or more medium/high-dose inhaled corticosteroid plus additional therapy within the 12 months preceding delivery. Poor control was defined as having at least 1 of the following: 1 or more exacerbation (asthma-related hospitalization or emergency room visit, or a course of oral corticosteroids) or 5 or more filled prescriptions for short-acting ß-agonists between the last menstrual period and delivery. RESULTS: Among 604,420 pregnant women in MarketScan and 2,071,359 in MAX, 20,104 (3.3%) and 120,745 (5.8%) had asthma, respectively. Among pregnant women with asthma, 19.0% and 18.8% had severe asthma and 16.5% and 28.0% had poorly controlled asthma in MarketScan and MAX, respectively. Many women with poorly controlled asthma during pregnancy were not dispensed a long-term controller (38.4% in MarketScan and 43.3% in MAX). Within both cohorts, women with poor control were more often smokers and obese, had more comorbidities, and used more concomitant nonasthma medications. CONCLUSIONS: Poorly controlled asthma is more frequent among publicly versus privately insured pregnancies in the United States. Dispensing of long-term controller medications during pregnancy remains low, even for symptomatic patients.

Use of clinical characteristics to predict spirometric classification of obstructive lung disease.

Background: There is no consensus on how to define patients with symptoms of asthma and chronic obstructive pulmonary disease (COPD). A diagnosis of asthma-COPD overlap (ACO) syndrome has been proposed, but its value is debated. This study (GSK Study 201703 [NCT02302417]) investigated the ability of statistical modeling approaches to define distinct disease groups in patients with obstructive lung disease (OLD) using medical history and spirometric data. Methods: Patients aged ≥18 years with diagnoses of asthma and/or COPD were categorized into three groups: 1) asthma (nonobstructive; reversible), 2) ACO (obstructive; reversible), and 3) COPD (obstructive; nonreversible). Obstruction was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7, and reversibility as a post-albuterol increase in FEV1 ≥200 mL and ≥12%. A primary model (PM), based on patients' responses to a health care practitioner-administered questionnaire, was developed using multinomial logistic regression modeling. Other multivariate statistical analysis models for identifying asthma and COPD as distinct entities were developed and assessed using receiver operating characteristic (ROC) analysis. Partial least squares discriminant analysis (PLS-DA) assessed the degree of overlap between groups. Results: The PM predicted spirometric classifications with modest sensitivity. Other analysis models performed with high discrimination (area under the ROC curve: asthma model, 0.94; COPD model, 0.87). PLS-DA identified distinct phenotypic groups corresponding to asthma and COPD. Conclusion: Within the OLD spectrum, patients with asthma or COPD can be identified as two distinct groups with a high degree of precision. Patients outside these classifications do not constitute a homogeneous group.

Disease Burden of Patients with Asthma/COPD Overlap in a US Claims Database: Impact of ICD-9 Coding-based Definitions.

The inclusion of an asthma/chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) population in the 2015 Global Initiative for Chronic Obstructive Lung Disease strategic documents has raised questions about the profile of these patients in clinical practice, as they are mostly excluded from asthma and COPD clinical trials. We estimated the disease burden, co-morbidities, and respiratory treatments of patients with asthma/COPD overlap, utilizing the Truven MarketScan commercial and Medicare databases. Patients with ≥1 COPD or chronic obstructive asthma diagnostic code were identified between January 1, 2008, and December 31, 2011. The asthma/COPD overlap group was defined and stratified based upon type and frequency of asthma diagnostic code (chronic obstructive asthma only, COPD and chronic obstructive asthma, and COPD and ≥1 asthma code). 1,488,613 patients were identified; of these, 1,171,626 were diagnosed with COPD alone and 316,987 with asthma/COPD overlap. Patients with asthma and COPD had higher disease burden indicators and inhaled corticosteroid/long-acting beta-agonist use compared with COPD alone. This trend was consistent for all definitions of asthma/COPD overlap. Patients with obstructive asthma and COPD tended to be older, with greater disease burden compared with other definitions; this population may represent a more severe form of asthma/COPD overlap. Disease burden and treatment also varied based on the codes defining asthma/COPD overlap, indicating possible phenotypic differences. More clinical insight and detailed phenotyping is needed to determine the reasons for coding variation in asthma/COPD overlap, with implications for further research to address unmet needs.

A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings.

BACKGROUND: Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE: The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS: Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS: A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father. CONCLUSIONS: An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.

Understanding asthma-chronic obstructive pulmonary disease overlap syndrome.

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a loosely-defined clinical entity referring to patients who exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD). Clinical definitions and classifications for ACOS vary widely, which impacts our understanding of prevalence, diagnosis and treatment of the condition. This literature review was therefore conducted to characterize the prevalence of ACOS and the effect of different disease definitions on these estimates, as this has not previously been explored. From an analysis of English language literature published from 2000 to 2014, the estimated prevalence of ACOS ranges from 12.1% to 55.2% among patients with COPD and 13.3%-61.0% among patients with asthma alone. This variability is linked to differences in COPD and asthma diagnostic criteria, disease ascertainment methods (spirometry-based versus clinical or symptom-based diagnoses and claims data), and population characteristics including age, gender and smoking. Understanding the reasons for differences in prevalence estimates of ACOS across the literature may help guide decision making on the most appropriate criteria for defining ACOS and aid investigators in designing future ACOS clinical studies aimed at effective treatment.

Characteristics of patients with COPD newly prescribed a long-acting bronchodilator: a retrospective cohort study.

INTRODUCTION: This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD) newly prescribed a long-acting bronchodilator (LABD), and to assess changes in medication over 24 months. METHODS: A cohort of patients with COPD aged ≥40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan(®) Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA) and followed for 24 months. Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline). Patient characteristics were examined. As LABDs were mainly long-acting muscarinic antagonists (LAMAs), additions, switches, discontinuation, adherence to (medication possession ratio), and persistence (proportion of days covered) with LAMA monotherapy were assessed for 24 months following the index date. Adherence and persistence with long-acting ß2-agonists (LABAs) were also assessed. RESULTS: A cohort of 3,268 patients aged 40-65 years was identified (mean age 55.8 years, 48% male). LAMA monotherapy was prescribed to 93% of patients who received an LABD. During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline. Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively. Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively. CONCLUSION: Adherence to newly initiated LAMA monotherapy was low, with one in four patients adding to or switching from LAMA and many patients discontinuing therapy. Adherence to LABA was also low. These results suggest that additional medication to a single LABD may be required in some patients with COPD to achieve optimal disease control.

Treatment evolution after COPD diagnosis in the UK primary care setting.

RATIONALE: To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting. METHODS: A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009. Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed. Treatment classes included long-acting ß2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations. At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up. RESULTS: A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis. At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%). Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months. Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months. Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months. CONCLUSION: Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline. The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.

Respiratory pharmacotherapy use in patients newly diagnosed with chronic obstructive pulmonary disease in a primary care setting in the UK: a retrospective cohort study.

This retrospective cohort study aimed to analyze the prescribing practices of general practitioners treating patients with newly diagnosed chronic obstructive pulmonary disease (COPD), and to assess characteristics associated with initial pharmacotherapy. Patients were identified in the General Practice Research Database, a population-based UK electronic medical record (EMR) with data from January 1, 2008 to December 31, 2009. Patient characteristics, prescribed COPD pharmacotherapies (≤12 months before diagnosis and within 3 months following diagnosis), co-morbidities, hospitalizations, and events indicative of a possible COPD exacerbation (≤12 months before diagnosis) were analyzed in 7881 patients with newly diagnosed COPD. Most patients (64.4%) were prescribed COPD pharmacotherapy in the 12 months before diagnosis. Following diagnosis, COPD pharmacotherapy was prescribed within 3 months in 85.0% of patients. Short-acting bronchodilators alone (22.9%) or inhaled corticosteroids + long-acting beta-2 agonists (ICS+LABA, 22.1%) were prescribed most frequently. Compared with other pharmacotherapies, the prevalence of severe airflow limitation was highest in patients prescribed ICS+LABA+long-acting muscarinic antagonists (LAMA). Moderate-to-severe dyspnea was identified most frequently in patients prescribed a LAMA-containing regimen. Patients prescribed an ICS-containing regimen had a higher prevalence of asthma or possible exacerbations recorded in the EMR than those not prescribed ICS. In conclusion, pharmacotherapy prescribed at initial COPD diagnosis varied by disease severity indicators as assessed by airflow limitation, dyspnea, history of asthma, and possible exacerbations. Frequent prescription of COPD pharmacotherapies before the first-recorded COPD diagnosis indicates a delay between obstructive lung disease presentation in primary care practice and assignment of a medical diagnosis.

First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies.

BACKGROUND: Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta-analysis was conducted. METHODS: A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed-effect summary estimates were calculated and sensitivity analyses performed. RESULTS: Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17-1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08-1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects. CONCLUSIONS: This meta-analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects.

Evaluation of the General Practice Research Database congenital heart defects prevalence: comparison to United Kingdom national systems.

BACKGROUND: As part of an effort to validate the General Practice Research Database (GPRD) for future studies of medication use in pregnancy, this study examined whether the rates of all, and specific types of, congenital heart defects obtained from the GPRD are similar to those obtained from UK national systems. METHODS: The prevalence rates of heart defects for 2001-2003 were determined from the GPRD and compared with both the National Congenital Anomaly System (NCAS) and the European Concerted Action of Congenital Anomalies and Twins (EUROCAT). Rate ratios (RRs) and 95% CIs were calculated comparing the prevalence of all congenital heart defects as well as specific types of heart defects in the three data sources. In addition, the effect of the child's age on the frequency of heart defects in the GPRD was determined. RESULTS: The prevalence of heart defects in the GPRD was more than twice as high as in the NCAS and slightly higher than in the EUROCAT. All differences were statistically significant. The prevalence of specific heart defects varied across the GPRD, NCAS, and EUROCAT. The measured prevalence of congenital heart defects in the GPRD was higher if calculated including children up to age 6. CONCLUSIONS: The comparisons of the GPRD prevalence rates to national prevalence estimates demonstrate that the GPRD can serve as a more complete source of background prevalence for the most commonly occurring congenital heart defects, which is essential to properly assess possible associations between maternal exposures and congenital heart defects.

Physician knowledge and adherence to prescribing antibiotic prophylaxis for sickle cell disease.

OBJECTIVE: The purpose of this research was to examine how physician characteristics were associated with: (i). physician knowledge of and adherence to sickle cell guidelines; and (ii). the types of educational programs about sickle cell disease desired by physicians. METHODS: A survey was developed to assess the research objective. After the survey was pre-tested and an institutional review board exemption was obtained, it was sent to a systematic random sample of 375 pediatricians and all 125 practicing hematologists in North Carolina. They were asked to answer a six-item knowledge test relating to the antibiotic prophylaxis guidelines. RESULTS: The response rate was 57%, of which 61% were pediatricians. Over half (56%) were in a practice with at least one pediatric sickle cell patient. Fifty-nine percent of physicians answered five or more questions correctly on the knowledge test. The question most physicians answered correctly (97%) pertained to the necessity of antibiotics for children with sickle cell disease. The question most frequently answered incorrectly (62%) pertained to prescribing antibiotics to a child with unconfirmed sickle cell disease. Logistic regression results indicated that the number of sickle cell patients seen in practice influenced the number of questions answered correctly. Sixty-six percent of physicians prescribed prophylactic antibiotics for 100% of their patients with sickle cell disease and therefore were 100% adherent. Eighty-one percent of pediatricians compared with 12% of hematologists were 100% adherent in prescribing antibiotics. Hematologists and those practicing at a medical school or university were less likely to be 100% adherent in prescribing antibiotic prophylaxis. CONCLUSION: The majority of physicians surveyed were relatively knowledgeable about sickle cell guidelines, however there may be a need for continuing education programs that focus on the issues of prescribing antibiotics to a child with unconfirmed sickle cell disease and penicillin dosage.

Physicians' perceptions of factors influencing adherence to antibiotic prophylaxis in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) aged <5 years are at great risk for invasive infection with Staphylococcus pneumoniae and Haemophilus influenzae due to the inability of their spleen to protect against infection. OBJECTIVES: This study examined (1) physicians' perceptions of factors associated with adherence to antibiotic prophylaxis in children with SCD and (2) how physician characteristics are associated with these perceptions. METHODS: A MEDLINE search of the years 1996 to 2002, using the terms sickle cell disease, compliance, children, physician perceptions, and antibiotic prophylaxis, was done. A survey was developed using existing literature to assess physicians' perceptions of factors associated with adherence to antibiotic prophylaxis for SCD. The survey was sent to a stratified random sample of 375 pediatricians and all 125 practicing hematologists in North Carolina. They were given a Likert-type scale to assess their perceptions of factors that influence patients' adherence to antibiotic prophylaxis for SCD. Physician demographic information was collected using the North Carolina Health Professions Data Book. The demographic information was matched to the survey respondent and correlated with his or her responses. RESULTS: The response rate was 56.9%. Of the respondents, 60.9% were pediatricians, and 56.5% were in a practice with at least 1 patient aged <5 years with SCD. Physician race and practice specialty were significantly associated with factors physicians considered very important to adherence. CONCLUSIONS: Most physicians agree on many issues that affect adherence; however, significant and important differences exist, based on physician ethnicity. Physicians' perceptions of factors that affect adherence in this study did not always agree with factors demonstrated to actually affect adherence in SCD patients. Therefore, this study indicates a need for physician continuing-education programs that focus on factors that actually influence adherence of antibiotic prophylaxis and the racial/ethnic backgrounds of the providers in relation to the patient.