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IntroductionUnderstanding the level of recording of acute serious events in general practice electronic health records (EHRs) is critical for making decisions about the suitability of general practice datasets to address research questions and requirements for linking general practice EHRs with other datasets.
ObjectivesTo examine data source agreement of five serious acute events (myocardial infarction, stroke, venous thromboembolism (VTE), pancreatitis and suicide) recorded in general practice EHRs compared with hospital, emergency department (ED) and mortality data.
MethodsData from 61 general practices routinely contributing data to the MedicineInsight database was linked with New South Wales administrative hospital, ED and mortality data. The study population comprised patients with at least three clinical encounters at participating general practices between 2019 and 2020 and at least one record in hospital, ED or mortality data between 2010 and 2020. Agreement was assessed between MedicineInsight diagnostic algorithms for the five events of interest and coded diagnoses in the administrative data. Dates of concordant events were compared.
ResultsThe study included 274,420 general practice patients with at least one record in the administrative data between 2010 and 2020. Across the five acute events, specificity and NPV were excellent (>98%) but sensitivity (13%-51%) and PPV (30%-75%) were low. Sensitivity and PPV were highest for VTE (50.9%) and acute pancreatitis (75.2%), respectively. The majority (roughly 70-80%) of true positive cases were recorded in the EHR within 30 days of administrative records.
ConclusionLarge proportions of events identified from administrative data were not detected by diagnostic algorithms applied to general practice EHRs within the specific time period. EHR data extraction and study design only partly explain the low sensitivities/PPVs. Our findings support the use of Australian general practice EHRs linked to hospital, ED and mortality data for robust research on the selected serious acute conditions.

Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990–1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans' reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans' severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78–9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02–5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01–5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of ...

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.