Background Studies indicate unwarranted variation in a wide range of neonatal care practices, contributing to preventable morbidity and mortality. Unwarranted variation is the result of complex... Show moreBackground Studies indicate unwarranted variation in a wide range of neonatal care practices, contributing to preventable morbidity and mortality. Unwarranted variation is the result of complex interactions and multiple determinants. One of the determinants contributing to unwarranted variation in care may be variation in local hospital protocols. The purpose of this study was to examine variation in the content of obstetric and neonatal protocols for six common indications for neonatal referral to the pediatrician: large for gestational age/macrosomia, small for gestational age/fetal growth restriction, meconium-stained amniotic fluid, vacuum extraction, forceps extraction, and cesarean birth. Methods We conducted a nationwide cross-sectional study examining protocols for neonatal referral to the pediatrician in the obstetric and neonatal departments of all Dutch hospitals. Variation in protocols was analyzed between regions, between neonatal and obstetrics departments located in the same hospital, and within neonatal and obstetrics departments. Results There was considerable variation in protocols between regions, between neonatal and obstetrics departments, and within neonatal and obstetrics departments. The results of this study showed considerable variation in recommendations for type of referral, admission, screening/diagnostic tests, treatment, and discharge. Furthermore, results generally showed lower referral thresholds in neonatal departments compared with obstetric departments, and higher referral thresholds in the eastern region of the Netherlands. We also found variation in local hospital protocols, which could not be explained by population characteristics but which may be explained by varying recommendations in existing national and international guidelines and/or lack of adherence to these guidelines. Conclusions To reduce unwarranted variation in local protocols, evidence-based, multidisciplinary guidelines should be developed in the Netherlands. Further research addressing knowledge gaps is needed to inform these guidelines. Attention should be paid to the implementation of evidence, and only where evidence is lacking or inconclusive should agreements be based on multidisciplinary consensus. Where protocols deviate from evidence-based guidelines because of specific local circumstances, clearer, more transparent justifications should be made. Uniformity in guidance will offer clear standards for care evaluation and provide opportunities to reduce inappropriate care. Show less
BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising... Show moreBACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development. Show less