Sanders SJ, Sahin M, Hostyk J, Thurm A, Jacquemont S, Avillach P, Douard E, Martin CL, Modi ME, Moreno-De-Luca A, Raznahan A, Anticevic A, Dolmetsch R, Feng G, Geschwind DH, Glahn DC, Goldstein DB, Ledbetter DH, Mulle JG, Pasca SP, Samaco R, Sebat J, Pariser A, Lehner T, Gur RE, Bearden CE.
A framework for the investigation of rare genetic disorders in neuropsychiatry. Nat Med 2019;25(10):1477-1487.
AbstractDe novo and inherited rare genetic disorders (RGDs) are a major cause of human morbidity, frequently involving neuropsychiatric symptoms. Recent advances in genomic technologies and data sharing have revolutionized the identification and diagnosis of RGDs, presenting an opportunity to elucidate the mechanisms underlying neuropsychiatric disorders by investigating the pathophysiology of high-penetrance genetic risk factors. Here we seek out the best path forward for achieving these goals. We think future research will require consistent approaches across multiple RGDs and developmental stages, involving both the characterization of shared neuropsychiatric dimensions in humans and the identification of neurobiological commonalities in model systems. A coordinated and concerted effort across patients, families, researchers, clinicians and institutions, including rapid and broad sharing of data, is now needed to translate these discoveries into urgently needed therapies.
Alexander M, Loomis KA, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Avillach P, Egger P, Dhalwani NN, Kendrick S, Celis-Morales C, Waterworth DM, Alazawi W, Sattar N.
Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ 2019;367:l5367.
AbstractOBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).
DESIGN: Matched cohort study.
SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046).
PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database.
MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses.
RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension.
CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.
Zhong Q-Y, Mittal LP, Nathan MD, Brown KM, Knudson González D, Cai T, Finan S, Gelaye B, Avillach P, Smoller JW, Karlson EW, Cai T, Williams MA.
Use of natural language processing in electronic medical records to identify pregnant women with suicidal behavior: towards a solution to the complex classification problem. Eur J Epidemiol 2019;34(2):153-162.
AbstractWe developed algorithms to identify pregnant women with suicidal behavior using information extracted from clinical notes by natural language processing (NLP) in electronic medical records. Using both codified data and NLP applied to unstructured clinical notes, we first screened pregnant women in Partners HealthCare for suicidal behavior. Psychiatrists manually reviewed clinical charts to identify relevant features for suicidal behavior and to obtain gold-standard labels. Using the adaptive elastic net, we developed algorithms to classify suicidal behavior. We then validated algorithms in an independent validation dataset. From 275,843 women with codes related to pregnancy or delivery, 9331 women screened positive for suicidal behavior by either codified data (N = 196) or NLP (N = 9,145). Using expert-curated features, our algorithm achieved an area under the curve of 0.83. By setting a positive predictive value comparable to that of diagnostic codes related to suicidal behavior (0.71), we obtained a sensitivity of 0.34, specificity of 0.96, and negative predictive value of 0.83. The algorithm identified 1423 pregnant women with suicidal behavior among 9331 women screened positive. Mining unstructured clinical notes using NLP resulted in a 11-fold increase in the number of pregnant women identified with suicidal behavior, as compared to solely reliance on diagnostic codes.