Final results from the ribavirin pregnancy registry, 2004-2020.

INTRODUCTION: Significant teratogenic effects have been demonstrated for ribavirin in animal studies. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in pregnant women and their male sexual partners. Both are advised to avoid pregnancy for 6 months after exposure. The registry monitored pregnancy exposures to oral formulations of ribavirin for hepatitis C for signals of possible human teratogenicity from 2004 to 2020. METHODS: Pregnant women were voluntarily enrolled following direct exposure (ribavirin use during pregnancy or the 6 months prior) or indirect exposure (through sexual contact during pregnancy or 6 months prior, with a man who has taken ribavirin within 6 months). Women were followed until the end of pregnancy. Infants were followed until 1 year of age. Birth defect rates were compared with the published rate of 2.67 per 100 live births from the Metropolitan Atlanta Congenital Defects Program (MACDP). RESULTS: The registry enrolled 280 pregnancies resulting in 186 live births: eight birth defect cases among 88 directly exposed [9.09% (8/88, 95% CI: 4.01, 17.13)], and six birth defect cases among 98 indirectly exposed [6.12% (6/98, 95% CI: 2.28, 12.85)]. The 95% CI around the birth defect rate among directly exposed pregnancies exceeds the MACDP rate; however, no patterns suggestive of a teratogenic mechanism or safety signal were detected. CONCLUSION: Based on the patterns of birth defects reported, the final results from this registry do not suggest a clear signal of human teratogenicity for ribavirin. The registry did not meet sample size requirements; therefore, caution should be exercised when interpreting the results.

Risk of interstitial lung disease in patients treated for atrial fibrillation with dronedarone versus other antiarrhythmics.

PURPOSE: To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. METHODS: Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1-year baseline and minimum 6 months of follow-up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. RESULTS: A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1-5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4-2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. CONCLUSIONS: ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Outcomes Associated with Dronedarone Use in Patients with Atrial Fibrillation.

The antiarrhythmic drug dronedarone was designed to reduce the extra-cardiac adverse effects associated with amiodarone use in treatment of patients with atrial fibrillation / atrial flutter (AF/AFL). This epidemiological study used a retrospective cohort design to compare risk of cardiovascular-related hospitalizations and death in AF/AFL patients treated with dronedarone versus other antiarrhythmic drugs (AADs). AF/AFL patients with incident dronedarone fills were matched by propensity score (PS) to incident users of other AADs. The primary study outcome was hospitalization for cardiovascular (CV) causes within 24 months after the first study drug fill. A secondary composite outcome comprised hospitalization for CV causes or all-cause mortality during follow-up. In the AF/AFL patient cohort meeting eligibility criteria, 6,964 incident users of dronedarone and 25 607 incident users of other AADs were identified. The PS-matched cohort comprised 6,349 Dronedarone users (91.2% of all eligible) and 12,698 other AAD users. Dronedarone patients had a significantly lower risk of hospitalization for a CV event compared to Other AAD users (hazard ratio = 0.87; 95% confidence interval = 0.79 to 0.96). This was consistent with results for the composite outcome (hazard ratio=0.86; 95% confidence interval = 0.78 to 0.95). In conclusion, AF/AFL patients initiated on dronedarone versus other AADs had significantly lower risk of CV hospitalizations as well as the composite CV hospitalization / death from any cause.

Modafinil and the risk of cardiovascular events: Findings from three US claims databases.

PURPOSE: This study examined the potential risk of cardiovascular (CV) events associated with modafinil and the consistency of the risk estimates across databases. METHODS: A retrospective, inception cohort design of patients who initiated treatment with modafinil between 2006 and 2008 was used in three US health care claims databases. Modafinil users were matched with nonusers. Patients were further divided into two cohorts of obstructive sleep apnea (OSA) and non-OSA (NOSA) cohorts. Endpoints of interest, including myocardial infarction (MI), stroke, CV hospitalizations, and all-cause death, were assessed using incidence rates and Cox proportional hazard ratios (HRs), adjusted for potential confounding factors. RESULTS: The cohorts included a total of 175 524 patients in MarketScan CM; 77 266-in IMS LifeLink; and 8174-in MarketScan Medicaid. No increased risk for MI in the OSA and NOSA cohorts was observed across all three databases. The risks of CV hospitalization in the OSA and NOSA cohorts were not different between the modafinil users and nonusers, except for IMS LifeLink database where the HR was lower than one in the modafinil users compared with the nonusers (HR, 0.69; 95% confidence interval [CI], 0.54 to 0.87). For OSA patients with prior stroke, an adjusted HR of 1.96 (95% CI, 1.02 to 3.76) was observed for stroke among modafinil users compared with nonusers. Among the NOSA, the HRs for all-cause death in the OSA were inconsistent across databases. CONCLUSIONS: Except for few CV outcomes, applying one common protocol generated consistent risk estimates of CV events following modafinil use across cohorts and databases.

Long-term risk of hysterectomy and ectopic pregnancy among Vietnamese women using the quinacrine hydrochloride pellet system vs. intrauterine devices or tubal ligation for contraception.

OBJECTIVES: Determine the long-term risk of hysterectomy and ectopic pregnancy in women using the quinacrine hydrochloride pellet system of permanent contraception (QS) relative to the comparable risk in women using Copper T intrauterine device (IUD) or tubal ligation surgery (TL) for long-term or permanent contraception. METHODS: This was a retrospective cohort study, conducted in the Northern Vietnamese provinces of Ha Nam, Nam Dinh, Ninh Binh and Thai Binh. Women who had their first QS procedure, last IUD insertion or TL between 1989 and 1996 were interviewed regarding post-procedure health outcomes approximately 16 years post exposure. RESULTS: A 95% response rate resulted in 21,040 completed interviews. Overall incidence rates were low for both outcomes (91/100,000 women years of follow-up and 22/100,000 women years of follow-up for hysterectomy and ectopic pregnancy, respectively). After accounting for variations in baseline characteristics between women choosing QS vs. the other two contraceptive methods, no significant excess hazard of either hysterectomy or ectopic pregnancy was associated with QS. CONCLUSIONS: No significant excess long-term risk of hysterectomy or ectopic pregnancy was found among a large group of women using QS vs. IUD or TL for contraception after an average 16 years of follow-up.

The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment.

INTRODUCTION: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity. METHODS: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct-women taking ribavirin during pregnancy or the 6 months prior to conception-or indirect-women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program's published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated. RESULTS: The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen. CONCLUSION: Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00114712.

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. PERSPECTIVE: Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation.

Long-term risk of reproductive cancer among Vietnamese women using the quinacrine hydrochloride pellet system vs. intrauterine devices or tubal ligation for contraception.

OBJECTIVES: To determine the long-term risk of reproductive tract cancer in women using the quinacrine hydrochloride pellet system of permanent contraception (QS) relative to the comparable risk in women using Copper T intrauterine device (IUD) or tubal ligation surgery (TL) for long-term or permanent contraception. METHODS: This was a retrospective cohort study, conducted in the Northern Vietnamese provinces of Ha Nam, Nam Dinh, Ninh Binh and Thai Binh. Women who had their first QS procedure, last IUD insertion or TL between 1989 and 1996 were interviewed regarding post-procedure health outcomes, particularly reproductive tract cancers. RESULTS: A 95% response rate resulted in 21,040 completed interviews. Reproductive cancer incidence rates were very low (5.77/100,000 women years of follow-up time; 95%CI = 3.72-8.94). No significant excess hazard of reproductive tract cancer was associated with QS. CONCLUSIONS: No significant excess long-term risk of reproductive tract cancer was found after an average 16 years of follow-up among a large group of women using QS vs. IUD/TL for contraception.

Intranasal Fluticasone Propionate Observational Cohort Safety Studies: Reviewing Evidence from Databases on Two Continents.

PURPOSE: Our objective was to highlight the importance of database selection in observational research and to determine the incidence of corticosteroid-related events in patients exposed to fluticasone propionate intranasal spray (FPNS) compared with other intranasal steroids (INS). METHODS: After a feasibility study using an electronic medical record database in the UK (1990-2002), a retrospective cohort study was conducted using a large administrative claims database in the USA from 1994 to 2002 comparing the incidence and rate ratios of steroid-related events among intermittent, sub-chronic, and chronic FPNS use and other INS use episodes. RESULTS: Most patients used INS intermittently; power was low to evaluate risk associated with chronic use. Significantly elevated adjusted rate ratios were observed in the US study comparing FPNS with other INS for hypercorticism, sinusitis, abscess, and empyema, as well as a significantly decreased rate ratio for cataracts. The US claims database provided greater granularity on covariates and markers of severity to improve control of confounding for this study and time period, but neither database was able to assess the indication for prescription and the UK study could not address the use of INS without a prescription. CONCLUSIONS: The FPNS results were consistent with the risk profile for INS and did not raise any new safety signals at the time of study conduct, which is consistent with the current safety profile. We were not able to discern the extent of potential off-label use of FPNS or other INS. Differences in the available data and healthcare systems highlight important considerations for database selection in the feasibility phase to assess the precision and limitations prior to formal risk evaluation.

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

BACKGROUND AND OBJECTIVES: Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. METHODS: The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. RESULTS: The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. DISCUSSION AND CONCLUSIONS: MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. SCIENTIFIC SIGNIFICANCE: Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651).

Hospitalized cardiovascular events in patients with diabetic macular edema.

BACKGROUND: Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases. METHODS: This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January 2002 to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and CVA events were then calculated. RESULTS: The adjusted rate ratio for MI was 2.50 (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI events were heart disease, history of acute MI, and prior use of antiplatelet or anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83, p < 0.001) for DME versus diabetes controls. Predictors of CVA events were cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia, and other cerebrovascular diseases. CONCLUSION: Event rates of MI or CVA were higher in patients with DME than in diabetes controls. This study is one of few with sufficient sample size to accurately estimate the relationship between DME and cardiovascular outcomes.

Risk of significant infection in rheumatoid arthritis patients switching anti-tumor necrosis factor-α drugs.

OBJECTIVES: To describe rates of first significant infection of rheumatoid arthritis patients who switch between anti-tumor necrosis factor (aTNF) drugs. METHODS: Subjects with rheumatoid arthritis who received only aTNF drugs were observed in an insurance claims database from January 2001 to December 2007. Nonswitchers (NS) remained on one aTNF throughout the study period (date of the first aTNF claim was the index date); switchers (S) received at least one other aTNF (claim date for the 2nd agent was the index date). Significant infections included those that required intravenous antibiotics or hospitalization. Two attributable risk periods were used: (1) an infection occurring ≤90 days following a claim for an aTNF (90-day) and (2) an infection occurring after the index date (ever-treated). Follow-up was censored at the first occurrence of a significant infection event, end of eligibility, or end of study period. Data were analyzed using Cox regression. RESULTS: In 13,752 NS and 2293 S patients, time-stratified rates declined 2- to 3-fold between the first year versus ≥2 years. Risk of significant infection was not different for either attribution model [90-day hazard ratio (HR) = 0.93, 95CI: 0.74 to 1.17, P = 0.55; ever treated HR = 0.94, 95CI: 0.78 to 1.15, P = 0.57]. First and second year rates were similar. Predictors included age ≥50 years; history of significant or opportunistic infection, diabetes, respiratory disease; Charlson score ≥2; or prior hospitalizations. CONCLUSIONS: The risk of a significant infection was not different between NS and S patients. Regardless of switching status, the rate of infection was greater in the first year. This study was limited by the lack of clinical data to determine the reason for switching.

Pharmacoepidemiology: defining the field and its core content.

PURPOSE: Emerging interests in pharmacoepidemiology make it important to define the profession's core content. The International Society for Pharmacoepidemiology (ISPE)'s Education Committee sought to develop a consensus on its core disciplines. This report recapitulates their efforts and conclusions. METHODS: The survey for skill inventories conducted characterized the field of pharmacoepidemiology by five categories of core competency/knowledge (pharmacovigilance, exposure data, epidemiology, clinical pharmacology, and medical product regulation) plus communication and leadership in these areas. It was sent to pharmacoepidemiology units within the industry, academia, and government representing the membership worldwide. RESULTS: After three waves, 125 members responded (~10% of the membership). Respondents were from North America (61%), European Union (23%), and the remainder from Asian Pacific and South American regions, representing the full spectrum of ISPE membership. Pharmacovigilance, analysis of exposure data, epidemiologic methods, and communication skills were the competencies identified as essential. Fourteen competencies were judged to be "essential" by >80% of the respondents; a further 26 had "essential" as the most frequently rated category but represented <80% of the respondents. Six items had "desirable but not a core competency" as the most commonly selected. None of the proposed competencies scored as "not a core competency" by >25% of the respondents. Only five of the competencies were suggested as "not core" by 10% or more. CONCLUSIONS: This survey identified a wide range of content relevant to the field of pharmacoepidemiology. This list will likely evolve over time. A curriculum around these areas will help prepare the next generation of pharmacoepidemiologists. Copyright © 2012 John Wiley & Sons, Ltd.

Validation of a claims-based diagnostic code for Stevens-Johnson syndrome in a commercially insured population.

PURPOSE: To validate the administrative claims identification of a diagnosis of Stevens-Johnson syndrome (SJS) using medical records as the "gold standard" in a large, commercially insured US population. METHODS: Patients with >1 medical claim with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x between 1 July 2000 and 31 May 2007 were queried in the HealthCore Integrated Research Database(SM) , which contains administrative claims data for 14 commercial health insurance plans. Trained nurses and pharmacists abstracted pertinent information from the identified patients' medical records, which were then reviewed by two independent dermatologists to identify criteria to determine SJS diagnosis. Positive predictive values (PPVs) based on the claims and chart data were computed for all the cases. RESULTS: Medical charts for 200 claims-identified cases, with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x, were abstracted and reviewed by the dermatologists. A total of five cases (PPV = 2.50%, 95%CI = 0.8%-5.7%) were determined to be SJS with clinical certainty. PPVs varied with data stratification: PPV for inpatient claims only (PPV = 2.00%, 95%CI = 0.24%-7.04%), inpatient claims with 695.1x in first diagnosis field (PPV = 4.11%, 95%CI = 0.86%-11.54%), and final decisions of either clinical certainty or probable cases of SJS (PPV = 6.00%, 95%CI = 3.14%-10.25%). CONCLUSION: These findings demonstrate the difficulties associated with identifying rare disorders, which lack specific diagnostic criteria, within administrative claims databases. They underscore the challenges of using claims data to monitor ill-defined clinical conditions as well as the need to validate claims-identified cases with information from other sources, such as medical charts. Copyright © 2012 John Wiley & Sons, Ltd.

Increasing rates of breast cancer and cardiac surveillance among high-risk survivors of childhood Hodgkin lymphoma following a mailed, one-page survivorship care plan.

BACKGROUND: Hodgkin lymphoma (HL) survivors face substantially elevated risks of breast cancer and cardiovascular disease. They and their physicians are often unaware of these risks and surveillance recommendations. PROCEDURE: A prospective one-arm study was conducted among a random sample of 72 HL survivors, ages 27-55 years, participating in the Childhood Cancer Survivor Study (CCSS) who were at increased risk for breast cancer and/or cardiomyopathy and had not had a screening mammogram or echocardiogram, respectively, within the prior 2 years. A one-page survivorship care plan with recommendations for surveillance was mailed to participants. In addition, survivors' primary physicians were contacted and provided patient-specific information and a web-based Virtual Information Center was made available for both survivors and physicians. Outcomes were assessed by telephone 6 months after the intervention. RESULTS: The survivor participation (62/72; 86%) and 6-month retention (56/61; 92%) rates were high. Tension and anxiety, measured by the Profile of Mood States, did not increase following risk notification; 91% of survivors described their reactions to receiving the information in positive terms. At 6 months, 41% of survivors reported having completed the recommended mammogram; 20% reported having an echocardiogram (females 30%, males 10%). Only 29% of survivors visited the website. Nine physicians enrolled, and none used the study resources. CONCLUSION: A mailed, personalized survivorship care plan was effective in communicating risk and increasing compliance with recommended medical surveillance. Internet- and telephone-based strategies to communicate risk were not utilized by survivors or physicians.

Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database.

AIMS: To characterize the patient profile, medication utilization, and healthcare encounters of patients with neurogenic bladder dysfunction related to incontinence. METHODS: Medical and pharmacy claims were retrospectively analyzed from April 1, 2002 to March 31, 2007 to characterize neurogenic bladder patients. There were 46,271 patients in the Neurogenic bladder cohort, and 9,315 and 4,168 patients in Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) subcohorts, respectively. Demographic data, concomitant diseases, use of overactive bladder (OAB) oral drug, and healthcare encounters were summarized using descriptive statistics. RESULTS: The mean age of neurogenic bladder patients was 62.5 (standard deviation 19.6) years. A high frequency of lower urinary tract infections (UTIs; 29%-36%), obstructive uropathies (6%-11%), and urinary retention (9%-14%), was observed. Overall, 33,100 (71.5%) patients were taking an OAB oral drug; 10,110 (30.5%) patients discontinued and did not restart. During the one-year follow-up period, 39.0% (8,034) of neurogenic bladder patients had a urology visit, 31.7% (14,679) had a neurology visit, 33.3% (15,415) were hospitalized, and 14.4% (6,646) were in a nursing home (highest rates observed in SCI subcohort). UTI diagnoses comprised over 20% of all hospitalizations one-year post-index. Annually, neurogenic bladder patients averaged 16 office and 0.5 emergency room visits. CONCLUSIONS: This is the largest observational study conducted to address the epidemiology of the neurogenic bladder population, including healthcare utilization. These data suggest that patients with neurogenic bladder may have suboptimal management, indicated by high incidences of urinary tract complications and hospitalizations.

Prevalence of pediatric dyslipidemia: comparison of a population-based claims database to national surveys.

OBJECTIVE: To determine the prevalence of pediatric dyslipidemia in a large US medical insurance claims database and to compare the resulting estimate to the prevalence from the National Health and Nutrition Examination Survey (NHANES). PATIENTS AND METHODS: Children 10-18 years old who had laboratory-defined dyslipidemia were identified from the Integrated Healthcare Information Services (IHCIS) database 2003-2006. For comparison purposes, the corresponding prevalence among the US children of same age was estimated from the NHANES 1999-2004 data. RESULTS: Among the 273 064 children with at least one laboratory lipid value in the IHCIS database, 22.9% (n = 62 451) had laboratory-defined dyslipidemia. This prevalence was the same as the NHANES estimate (23.9%, 95%CI: 21.6-26.3). Elevated triglyceride (TG) was the most common type of dyslipidemia, detected among 13.2% of the IHCIS children and 14.2% of the US children, followed by elevated total cholesterol (TC), 7.7 and 9.6%, respectively. Among IHCIS dyslipidemic children, older teenage boys had higher rates than younger boys for high-density lipoprotein cholesterol (HDL-C) abnormality, but lower rates for elevated TC and low-density lipoprotein cholesterol (LDL-C). These age-related trends were also seen among NHANES dyslipidemic children. CONCLUSIONS: Analyses of a population-based claims database revealed the same prevalence of pediatric dyslipidemia as that among the US children assessed in the NHANES data. Among dyslipidemic children in the claims database, the occurrence of specific dyslipidemias appeared to vary by age and gender, a trend that was also seen among the dyslipidemic children in the US.

The Ribavirin Pregnancy Registry: Findings after 5 years of enrollment, 2003-2009.

INTRODUCTION: Ribavirin, with interferons or pegylated interferons, is used to treat chronic hepatitis C. Ribavirin is contraindicated in pregnancy (FDA Pregnancy Category X) and in men whose partners may become pregnant. In 2003, the Ribavirin Pregnancy Registry was established to monitor pregnancy exposures to ribavirin and to evaluate the potential human teratogenicity of prenatal exposure. METHODS: This voluntary registry enrolls pregnant women who have been exposed to ribavirin during pregnancy or during the six months prior to conception either directly, by taking ribavirin, or indirectly through sexual contact with a man taking ribavirin. Women are followed until delivery; live born infants are followed for one year. The Registry aims to enroll 131 live births following direct (maternal) exposure to ribavirin and 131 live births following indirect (male) exposures. RESULTS: After more than five years of operation, the Registry has enrolled 49 live births with direct exposure and 69 live births following indirect exposure. Six outcomes with birth defects have been reported. All were among live born infants: torticollis (2), hypospadias (1), polydactyly and a neonatal tooth (1), glucose-6-phosphate dehydrogenase deficiency (1), ventricular septal defect and cyst of 4th ventricle of the brain (1). Three received direct exposures ([6.1% (95% CI: 1.2, 16.9)], three were exposed indirectly [4.3% (95% CI: 0.9, 12.2)]. CONCLUSIONS: Although current enrollment is far short of the required sample size, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin. However, findings must be interpreted with caution concerning direct or indirect prenatal ribavirin exposures.

Development and evaluation of an educational interactive CD-ROM for teens with cancer.

BACKGROUND: Cancer is the number one disease killer of children and adolescents in North America. For adolescents, this diagnosis comes at a particularly vulnerable stage. Educating adolescents with cancer from diagnosis through treatment teaches and empowers them. Increasing evidence shows that these adolescents want more information. Few educational tools exist for young cancer patients; none are interactive; therefore, a CD-ROM was developed to meet this need. PROCEDURE: Animation, voiceover, music, videos, and games were combined to develop a comprehensive multimedia CD-ROM to teach 12- to 18-year-olds with solid tumors about their disease, treatment, coping skills, and late effects in an interactive and non-threatening way. The CD-ROM was evaluated in a pre-post design with 65 subjects recruited from four pediatric oncology centers randomized to the CD-ROM or a "Handbook" containing analogous information. Pre-post questionnaires measured coping strategies, health locus of control, quality of life, cancer knowledge, and self-efficacy; post-test variables also included acceptability and use by teens, their families, and healthcare professionals. RESULTS: Teens receiving the CD-ROM were significantly more likely to increase their internal locus of control scores; however, no significant differences were observed on other measures, attributable in part to the study sample size. Among teens, acceptability was higher in the CD-ROM versus the Handbook group, but not different between the two parent groups. Pediatric oncology healthcare providers gave positive feedback on the CD-ROM. CONCLUSIONS: This CD-ROM is an innovative and engaging educational tool--the first portable interactive product with access on demand for adolescents with solid tumors.

Longitudinal study on pediatric dyslipidemia in population-based claims database.

PURPOSE: To examine the rate of lipid testing among children from a large US medical insurance claims database, describe the characteristics of pediatric dyslipidemia, and assess the sensitivity of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying dyslipidemic children. METHODS: This retrospective cohort study used the claims data from the Integrated Healthcare Information Services (IHCIS), for the years 2003-2006. Two study cohorts consisted of children with laboratory-defined and diagnosis/treatment-defined dyslipidemia, respectively. They were compared to age- and gender-matched children without dyslipidemia, with respect to co-morbidities during the 6-month prior to and 12-month after the first dyslipidemic laboratory value or diagnosis/treatment. RESULTS: Seven per cent of the children who had laboratory values available in the database had a cholesterol test during the study period. Only 15% of laboratory-defined children (n = 23,475) had a dyslipidemia diagnosis. Cholesterol-modifying medications were rarely prescribed. Substantially more laboratory-defined children than their comparators were obese (8 times), had diabetes mellitus (10 times), or had hypertension (5 times). These co-morbidities were even higher among diagnosis/treatment-defined children. CONCLUSIONS: The rate of lipid testing among children was low. The ICD-9-CM diagnostic codes showed low sensitivity against laboratory definitions. Though only a small proportion of dyslipidemic children were diagnosed or treated with a medication, co-morbidities associated with dyslipidemia were common.