Validation of a primary care electronic medical records case definition for eczema: retrospective cross-sectional study.

BACKGROUND: To validate case definitions for eczema using primary care Electronic Medical Record (EMR) data from the Canadian Primary Care Sentential Surveillance Network (CPCSSN). METHODS: This study used EMR data from 1,574 primary care providers in seven Canadian provinces, representing 689,301 patients. Using a subset of patient records seven medical students or family medicine residents created a reference set of 1,772 patients. A total of 23 clinician-informed case definitions were validated against the reference. We assessed agreement using sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and overall accuracy. The case definitions with the best agreement statistics were deployed to estimate the prevalence of eczema in the CPCSSN. RESULTS: Case definition 1 had the highest SE (92.1%,85.0-96.5) but a lower SP (88.5%,86.7-90.1) and PPV (36.6%,33.1-40.3). Case definition 7 was the most specific case definition with a SP (99.8%, 99.4-100) and PPV (84.2%,61.2-94.7) but low SE (15.8%,9.3-24.5). Case definition 17 had a SE (75.3%, 65.7-83.3), SP (93.8%, 91.5-94.3) and PPV 43.7% (38.3-49.2). When we applied the most specific and most sensitive case definitions, we estimate the prevalence of eczema to be between 0.8 and 15.1%. Case definition 17 suggests an eczema prevalence estimate of 8.2% (8.08-8.21%). CONCLUSIONS: We validated EMR-based eczema case definitions to estimate the prevalence of clinician-documented eczema. Future studies may choose to apply one or more of these definitions' dependent on their studies objectives to inform disease surveillance as well as explore burden of illness or interventions related to eczema care in Canada.

Primary care provider diagnosed eczema within electronic medical records from seven canadian provinces.

Context: Most epidemiological research on eczema has largely relied on patient survey data. With the increasing use of electronic medical records (EMR) in primary care, there has been a shift in epidemiological research towards the use of validated case definitions to study disease. Objective: Apply a validated case definition for eczema to EMR data from primary care providers participating in the Canadian Primary Care Sentential Surveillance Network (CPCSSN) to determine the prevalence of diagnosed eczema in Canada and describe patient's characteristics including risk factors and comorbidities. Study Design: Cross-sectional study. Dataset: EMR data from 1,574 primary care providers in seven Canadian provinces. Population Studied: Patient records were examined for those with at least one encounter with a family physician, nurse practitioner or community pediatrician participating in CPCSSN between January 1, 2017, and December 31, 2019 (N= 689,301 patients). Outcome Measures: Primary outcome was lifetime prevalence of eczema. Secondary outcomes were demographics of eczema patients and the association between eczema and various comorbidities. Results: Descriptive statistics revealed a lifetime prevalence of documented eczema of 11.6% overall, 15.1% in those <19 years, and 11.5% in those >19 years. Patients with eczema were more likely to be smokers. Using the Material and Social Deprivation Index we found eczema was more prevalent among the least materially and socially deprived quintiles. In logistic regression, female patients (OR, 1.29; 95% CI, 1.27-1.32) and patients <19 years (OR, 1.27; 95% CI, 1.19-1.35) had higher odds of eczema compared to male patients and patients aged >19 years. Patients with comorbidities such as rhinitis (OR, 2.11; 95% CI, 2.06-2.17), asthma (OR, 1.4; 95% CI, 1.37-1.43), any allergy (OR, 1.09, 95% CI 1.06-1.11), COPD (OR, 1.1; 95% CI, 1.06-1.14) and anxiety (OR, 1.66; 95% CI, 1.63-1.69) had higher odds of eczema compared to patients without these comorbidities. Depression (OR, 0.96; 95% CI, 0.94-0.98) and obesity (OR, 0.96; 95% CI, 0.94-0.98) were negatively associated with a diagnosis of eczema. Conclusion: This is the first study in Canada to determine the prevalence of primary care provider documented eczema using EMR data. This study can inform and improve disease surveillance as well as future studies exploring burden of illness, trends or interventions related to eczema care in Canada.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)/Drug-Induced Hypersensitivity Syndrome (DiHS)-Readdressing the DReSS.

Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe, systemic, T cell mediated drug reaction with combinations of cutaneous, hematologic, and internal organ involvement. Pathogenesis of DReSS is multi-factorial, involving drug-exposure, genetic predisposition through specific human leukocyte antigen (HLA) alleles and metabolism defects, viral reactivation, and immune dysregulation. Clinical features of this condition are delayed, stepwise, and heterogenous, making this syndrome challenging to recognize and diagnose. Two sets of validated diagnostic criteria exist that can be employed to diagnose DReSS/DiHS. Methods to improve early recognition of DReSS and predict disease severity has been a recent area of research focus. In vitro and in vivo tests can be employed to confirm the diagnosis and help identify culprit drugs. The mainstay treatment of DReSS is prompt withdrawal of the culprit drug, supportive treatment, and immunosuppression depending on the severity of disease. We present a comprehensive review on the most recent research and literature on DReSS, with emphasis on pathogenesis, clinical features, diagnosis, confirmatory testing modalities, and treatment. Additionally, this summary aims to highlight the differing viewpoints on this severe disease and broaden our perspective on the condition known as DReSS.

Oxolipidomics profile in major depressive disorder: Comparing remitters and non-remitters to repetitive transcranial magnetic stimulation treatment.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects. OBJECTIVES: To investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD. METHODS: Fourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission. RESULTS: Fifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p<0.05]. However, no significant changes in OxPC levels were found as a result of rTMS, regardless of treatment response [p>0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline. CONCLUSION: Certain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

Global DNA Methylation and Histone Posttranslational Modifications in Human and Nonhuman Primate Brain in Association with Prenatal Alcohol Exposure.

BACKGROUND: Based upon experimental animal studies, the neurodevelopmental abnormalities associated with prenatal alcohol exposure (PNAE)/fetal alcohol spectrum disorder (FASD) have been attributed, at least in part, to epigenetic modifications. However, there are no direct analyses of human brain tissue. METHODS: Immunohistochemical detection of global epigenetic markers was performed on temporal lobe samples of autopsied fetuses and infants with documented PNAE. They were compared to age-, sex-, and postmortem delay-matched control cases (18 pairs; 20 to 70.5 weeks postconception). Temporal lobe tissue from a macaque monkey model of PNAE was also studied (5.7 to 6 months of age). We used antibodies targeting 4 DNA cytosine, 4 histone methylation, and 6 histone acetylation modifications and assigned scores based upon the semiquantitatively graded intensity and proportion of positively labeled nuclei in the ventricular and subventricular zones, ependyma, temporal cortex, temporal white matter, dentate gyrus (DG), and CA1 pyramidal layer. RESULTS: Temporal changes were identified for almost all marks according to the state of maturation in the human brain. In the DG (and 3 other brain regions), a statistically significant increase in H3K9ac was associated with PNAE. Statistically significant decreases were seen among 5mC, H3K4me3, H3K9ac, H3K27ac, H4K12ac, and H4K16ac in select regions. In the macaques, H3K36me3 decreased in the DG, and the ependyma showed decreases in 5fC and H3K36me3. CONCLUSIONS: In human brain, global intranuclear epigenetic modifications are brain region and maturation state-specific. These exploratory results support the general hypothesis that PNAE is associated with a global decrease in DNA methylation, a global decrease in histone methylation, and a global increase in histone acetylation. Although the human and monkey subjects are not directly comparable in terms of brain maturation, considering the rapid temporal changes in global epigenetic modifications during brain development, interspecies comparisons may be extremely difficult.

DNA methylation and histone post-translational modification stability in post-mortem brain tissue.

BACKGROUND: Epigenetic (including DNA and histone) modifications occur in a variety of neurological disorders. If epigenetic features of brain autopsy material are to be studied, it is critical to understand the post-mortem stability of the modifications. METHODS: Pig and mouse brain tissue were formalin-fixed and paraffin-embedded, or frozen after post-mortem delays of 0, 24, 48, and 72 h. Epigenetic modifications frequently reported in the literature were studied by DNA agarose gel electrophoresis, DNA methylation enzyme-linked immunosorbent assays, Western blotting, and immunohistochemistry. We constructed a tissue microarray of human neocortex samples with devitalization or death to fixation times ranging from < 60 min to 5 days. RESULTS: In pig and mouse brain tissue, we found that DNA cytosine modifications (5mC, 5hmC, 5fC, and 5caC) were stable for ≥ 72 h post-mortem. Histone methylation was generally stable for ≥ 48 h (H3K9me2/K9me3, H3K27me2, H3K36me3) or ≥ 72 h post-mortem (H3K4me3, H3K27me3). Histone acetylation was generally less stable. The levels of H3K9ac, H3K27ac, H4K5ac, H4K12ac, and H4K16ac declined as early as ≤ 24 h post-mortem, while the levels of H3K14ac did not change at ≥ 48 h. Immunohistochemistry showed that histone acetylation loss occurred primarily in the nuclei of large neurons, while immunoreactivity in glial cell nuclei was relatively unchanged. In the human brain tissue array, immunoreactivity for DNA cytosine modifications and histone methylation was stable, while subtle changes were apparent in histone acetylation at 4 to 5 days post-mortem. CONCLUSION: We conclude that global epigenetic studies on human post-mortem brain tissue are feasible, but great caution is needed for selection of post-mortem delay matched controls if histone acetylation is of interest.