Birth and Neonatal Outcomes Following Opioid Use in Pregnancy: A Danish Population-Based Study.

BACKGROUND: Few population-based data exist on birth outcomes in women who received opioid maintenance treatment during pregnancy. We therefore examined adverse birth outcomes in women exposed to methadone or buprenorphine during pregnancy and the risk of neonatal abstinence syndrome (NAS) among neonates exposed to buprenorphine, methadone, and/or heroin in utero. PATIENTS AND METHODS: This study included all female Danish residents with a live birth or a stillbirth from 1997 to 2011. We identified the study population, use of opioids and opioid substitution treatment, birth outcomes, and NAS through medical registers. Birth outcomes included preterm birth (born before 38th gestational week), low-birth weight (LBW) (<2,500 g, restricted to term births), small for gestational age (SGA) (weight <2 standard deviations from the sex- and gestational-week-specific mean), congenital malformations, and stillbirths. We used log-binomial regression to estimate the prevalence ratio (PR) for birth outcomes. RESULTS: Among 950,172 pregnancies in a total of 571,823 women, we identified 557 pregnancies exposed to buprenorphine, methadone, and/or heroin (167 to buprenorphine, 197 to methadone, 28 to self-reported heroin, and 165 to combinations). Compared with nonexposed pregnancies, prenatal opioid use was associated with greater prevalence of preterm birth (PR of 2.8 (95% confidence interval (CI), 2.3-3.4)), LBW among infants born at term (PR of 4.3 (95% CI, 3.0-6.1)), and being SGA (PR of 2.7 (95% CI, 1.9-4.3)). Restricting the analyses to women who smoked slightly lowered these estimates. The prevalence of congenital malformations was 8.3% in opioid-exposed women compared with 4.2% in nonexposed women (PR of 2.0 (95% CI, 1.5-2.6)). The risk of NAS ranged from 7% in neonates exposed to buprenorphine only to 55% in neonates exposed to methadone only or to opioid combinations. CONCLUSION: The maternal use of buprenorphine and methadone during pregnancy was associated with increased prevalence of adverse birth outcomes, and this increase could only be explained to a smaller extent by increased prevalence of smoking. The risk of NAS was eight-fold higher in methadone-exposed neonates than that in buprenorphine-exposed neonates, but this difference may at least partly be explained by differences in underlying indications (analgesic versus opioid maintenance treatment) between the two groups.

Validation study in four health-care databases: upper gastrointestinal bleeding misclassification affects precision but not magnitude of drug-related upper gastrointestinal bleeding risk.

OBJECTIVE: To evaluate the accuracy of disease codes and free text in identifying upper gastrointestinal bleeding (UGIB) from electronic health-care records (EHRs). STUDY DESIGN AND SETTING: We conducted a validation study in four European electronic health-care record (EHR) databases such as Integrated Primary Care Information (IPCI), Health Search/CSD Patient Database (HSD), ARS, and Aarhus, in which we identified UGIB cases using free text or disease codes: (1) International Classification of Disease (ICD)-9 (HSD, ARS); (2) ICD-10 (Aarhus); and (3) International Classification of Primary Care (ICPC) (IPCI). From each database, we randomly selected and manually reviewed 200 cases to calculate positive predictive values (PPVs). We employed different case definitions to assess the effect of outcome misclassification on estimation of risk of drug-related UGIB. RESULTS: PPV was 22% [95% confidence interval (CI): 16, 28] and 21% (95% CI: 16, 28) in IPCI for free text and ICPC codes, respectively. PPV was 91% (95% CI: 86, 95) for ICD-9 codes and 47% (95% CI: 35, 59) for free text in HSD. PPV for ICD-9 codes in ARS was 72% (95% CI: 65, 78) and 77% (95% CI: 69, 83) for ICD-10 codes (Aarhus). More specific definitions did not have significant impact on risk estimation of drug-related UGIB, except for wider CIs. CONCLUSIONS: ICD-9-CM and ICD-10 disease codes have good PPV in identifying UGIB from EHR; less granular terminology (ICPC) may require additional strategies. Use of more specific UGIB definitions affects precision, but not magnitude, of risk estimates.

Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems: a validation study in three European countries.

OBJECTIVE: To evaluate positive predictive value (PPV) of different disease codes and free text in identifying acute myocardial infarction (AMI) from electronic healthcare records (EHRs). DESIGN: Validation study of cases of AMI identified from general practitioner records and hospital discharge diagnoses using free text and codes from the International Classification of Primary Care (ICPC), International Classification of Diseases 9th revision-clinical modification (ICD9-CM) and ICD-10th revision (ICD-10). SETTING: Population-based databases comprising routinely collected data from primary care in Italy and the Netherlands and from secondary care in Denmark from 1996 to 2009. PARTICIPANTS: A total of 4 034 232 individuals with 22 428 883 person-years of follow-up contributed to the data, from which 42 774 potential AMI cases were identified. A random sample of 800 cases was subsequently obtained for validation. MAIN OUTCOME MEASURES: PPVs were calculated overall and for each code/free text. 'Best-case scenario' and 'worst-case scenario' PPVs were calculated, the latter taking into account non-retrievable/non-assessable cases. We further assessed the effects of AMI misclassification on estimates of risk during drug exposure. RESULTS: Records of 748 cases (93.5% of sample) were retrieved. ICD-10 codes had a 'best-case scenario' PPV of 100% while ICD9-CM codes had a PPV of 96.6% (95% CI 93.2% to 99.9%). ICPC codes had a 'best-case scenario' PPV of 75% (95% CI 67.4% to 82.6%) and free text had PPV ranging from 20% to 60%. Corresponding PPVs in the 'worst-case scenario' all decreased. Use of codes with lower PPV generally resulted in small changes in AMI risk during drug exposure, but codes with higher PPV resulted in attenuation of risk for positive associations. CONCLUSIONS: ICD9-CM and ICD-10 codes have good PPV in identifying AMI from EHRs; strategies are necessary to further optimise utility of ICPC codes and free-text search. Use of specific AMI disease codes in estimation of risk during drug exposure may lead to small but significant changes and at the expense of decreased precision.

Positive predictive values of the coding for bisphosphonate therapy among cancer patients in the Danish National Patient Registry.

BACKGROUND: The purpose of this study was to estimate the positive predictive value (PPV) of the coding for bisphosphonate treatment in selected cancer patients from the Danish National Patient Registry (DNPR). METHODS: Through the DNPR, we identified all patients with recorded cancer of the breast, prostate, lung, kidney, and with multiple myeloma. We restricted the study sample to patients with bisphosphonate treatment recorded during an admission to Aalborg Hospital, Denmark, from 2005 through 2009. We retrieved and reviewed medical records of these patients from the initial cancer diagnosis onwards to confirm or rule out bisphosphonate therapy. We calculated the PPV of the treatment coding as the proportion of patients with confirmed bisphosphonate treatment. RESULTS: We retrieved and reviewed the medical records of 60 cancer patients with treatment codes corresponding to bisphosphonate therapy. Recorded code corresponded to treatment administered intravenously for 59 of 60 patients, corresponding to a PPV of 98.3% (95% confidence interval 92.5-99.8). In the remaining patient, bisphosphonate treatment was also confirmed but was an orally administered bisphosphonate; thus, the treatment for any bisphosphonate regardless of administration was confirmed for all 60 patients (PPV of 100%, 95% confidence interval 95.9-100.0). CONCLUSION: The PPV of bisphosphonate treatment coding among cancer patients in the DNPR is very high and the recorded treatment nearly always corresponds to intravenous administration.

Completeness of breast cancer staging in the Danish Cancer Registry, 2004-2009.

BACKGROUND: The purpose of this study was to investigate the completeness of TNM (Tumor, Node, Metastasis) staging for breast cancer in the Danish Cancer Registry. METHODS: We identified 26,488 patients with a first diagnosis of breast cancer between 2004 and 2009 from the Danish Cancer Registry. We obtained information on comorbidity through the Danish National Patient Registry. We estimated the completeness of TNM registration in the Danish Cancer Registry and stratified the analysis by gender, age, year of cancer diagnosis, and comorbidity. We designed an algorithm categorizing breast cancer into localized, regional, distant, or unknown stage based on TNM codes. RESULTS: The overall completeness of TNM registration was 85.4%. The completeness varied little by gender and study year, but decreased from 91.3% in patients aged 0-39 years to 57.0% in patients aged 80 years or more, and from 87.9% among patients with a low level of comorbidity to 69.7% among patients with a high level of comorbidity. CONCLUSION: The completeness of the TNM registration varied substantially by age and level of comorbidity. Thus, depending on the outcome under study, stage-specific analyses may yield biased results. The completeness of TNM should be considered in study designs using TNM information.