The Canadian Assisted Reproductive Technologies Register (CARTR) Plus database: a validation study.

STUDY QUESTION: Are data accurately documented in the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database? SUMMARY ANSWER: Measures of validity were strong for the majority of variables evaluated while those with moderate agreement were FSH levels, oocyte origin and elective single embryo transfer. WHAT IS KNOWN ALREADY: Health databases and registries are excellent sources of data. However, as these databases are typically not established for the primary purpose of performing research, they should be evaluated prior to utilization for research both to inform the study design and to determine the extent to which key study variables, such as patient characteristics or therapies provided, are accurately documented in the database. CARTR Plus is Canada's national register for collecting extensive information on IVF and corresponding pregnancy outcomes, and it has yet to be validated. STUDY DESIGN SIZE DURATION: This study evaluating the data translation CARTR Plus database examined IVF cycles performed in 2015 using data directly from patient charts. Six clinics across Canada were recruited to participate, using a purposive sampling strategy. Fixed random sampling was employed to select 146 patient cycles at each clinic, representing unique patients. Only a single treatment cycle record from a unique patient at each clinic was considered during chart selection. PARTICIPANTS/MATERIALS SETTING METHODS: Twenty-five data elements (patient characteristics, treatments and outcomes) were reabstracted from patient charts, which were declared the reference standard. Data were reabstracted by two independent auditors with relevant clinical knowledge after confirming inter-rater reliability. These data elements from the chart were then compared to those in CARTR Plus. To determine the validity of these variables, we calculated kappa coefficients, sensitivity, specificity, positive predictive value and negative predictive value with 95% CI for categorical variables and calculated median differences and intraclass correlation coefficients (ICC) for continuous variables. MAIN RESULTS AND THE ROLE OF CHANCE: Six clinics agreed to participate in this study representing five Canadian provinces. The mean age of patients was 35.5 years, which was similar between the two data sources, resulting in a near perfect level of agreement (ICC = 0.99; 95% CI: 0.99, 0.99). The agreement for FSH was moderate, ICC = 0.68 (95% CI: 0.64, 0.72). There was nearly perfect agreement for cycle type, kappa = 0.99 (95% CI: 0.98, 1.00). Over 90% of the cycles in the reabstracted charts used autologous oocytes; however, data on oocyte source were missing for 13% of cycles in CARTR Plus, resulting in a moderate degree of agreement, kappa = 0.45 (95% CI, 0.37, 0.52). Embryo transfer and number of embryos transferred had nearly perfect agreement, with kappa coefficients greater than 0.90, whereas that for elective single or double embryo transfer was much lower (kappa = 0.55; 95% CI: 0.49, 0.61). Agreement was nearly perfect for pregnancy type, and number of fetal sacs and fetal hearts on ultrasound, all with kappa coefficients greater than 0.90. LARGE-SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: CARTR Plus contains over 200 variables, of which only 25 were assessed in this study. This foundational validation work should be extended to other CARTR Plus database variables in future studies. WIDER IMPLICATIONS OF THE FINDINGS: This study provides the first assessment of the quality of the data translation process of the CARTR Plus database, and we found very high quality for the majority of the variables that were analyzed. We identified key data points that are either too often lacking or inconsistent with chart data, indicating that changes in the data entry process may be required. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Canadian Institutes of Health Research (CIHR) (Grant Number FDN-148438) and by the Canadian Fertility and Andrology Society Research Seed Grant (Grant Number: N/A). The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

A systematic review of database validation studies among fertility populations.

STUDY QUESTION: Are routinely collected data from fertility populations adequately validated? SUMMARY ANSWER: Of the 19 studies included, only one validated a national fertility registry and none reported their results in accordance with recommended reporting guidelines for validation studies. WHAT IS KNOWN ALREADY: Routinely collected data, including administrative databases and registries, are excellent sources of data, particularly for reporting, quality assurance, and research. However, these data are subject to misclassification bias due to misdiagnosis or errors in data entry and therefore need to be validated prior to using for clinical or research purposes. STUDY DESIGN SIZE DURATION: We conducted a systematic review by searching Medline, Embase, and CINAHL from inception to 6 October 2016 to identify validation studies of databases that contain routinely collected data in an ART setting. Webpages of international ART centers were also searched. PARTICIPANTS/MATERIALS SETTING METHODS: We included studies that compared at least two data sources to validate ART population data. Key words and MeSH terms were adapted from previous systematic reviews investigating routinely collected data (e.g. administrative databases and registries), measures of validity (including sensitivity, specificity, and predictive value), and ART (including infertility, IVF, advanced reproductive age, and diminished ovarian reserve). Only full-text studies in English were considered. Results were synthesized qualitatively. The electronic search yielded 1074 citations, of which 19 met the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Two studies validated a fertility database using medical records; seven studies used an IVF registry to validate vital records or maternal questionnaires, and two studies failed to adequately describe their reference standard. Four studies investigated the validity of mode of conception from birth registries; two studies validated diagnoses or treatments in a fertility database; four studies validated a linkage algorithm between a fertility registry and another administrative database; one study created an algorithm in a single database to identify a patient population. Sensitivity was the most commonly reported measure of validity (12 studies), followed by specificity (9 studies). Only three studies reported four or more measures of validation, and five studies presented CIs for their estimates. The prevalence of the variable in the target population (pre-test prevalence) was reported in seven studies; however, only four of the studies had prevalence estimates from the study population (post-test prevalence) within a 2% range of the pre-test estimate. The post-test estimate was largely discrepant from the pre-test value in two studies. LIMITATIONS REASONS FOR CAUTION: The search strategy was limited to the studies and reports published in English, which may not capture validation studies from countries that do not speak English. Furthermore, only three specific fertility-based diagnostic variables (advanced reproductive age, diminished ovarian reserve, and chorionicity) were searched in Medline, Embase, and CINAHL. Consequently, published studies with other diagnoses or conditions relevant to infertility may not have been captured in our review. WIDER IMPLICATIONS OF THE FINDINGS: There is a paucity of literature on validation of routinely collected data from a fertility population. Furthermore, the prevalence of the markers that have been validated are not being presented, which can lead to biased estimates. Stakeholders rely on these data for monitoring outcomes of treatments and adverse events; therefore, it is essential to ascertain the accuracy of these databases and make the reports publicly available. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Canadian Institutes of Health Research (CIHR) (FDN-148438). There are no competing interests for any of the authors. REGISTRATION NUMBER: International Prospective Register of Systematic Reviews ID: CRD42016048466.

Abnormal brain structure in youth who commit homicide.

BACKGROUND: Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. METHODS: Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). RESULTS: Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. CONCLUSIONS: Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses.

Cerebral palsy and chorioamnionitis: the inflammatory cytokine link.

Cerebral palsy remains a significant cause of perinatal morbidity in medically developed countries. Human epidemiologic data suggest a relationship between cerebral palsy and chorioamnionitis mediated by proinflammatory cytokines. This association has been confirmed by experimental data from human and animal research that demonstrate an increase in cytokine levels in the amniotic fluid of cases of white matter damage. Recent evidence suggests this damage is the result of a fetal inflammatory response initiated in response to placental inflammation. The strong association between cerebral palsy and chorioamnionitis warrants additional investigation into the mechanisms by which white matter damage is initiated and into possible neuroprotective treatments to prevent the development of cerebral palsy.