The Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing.

Background: Exome sequencing is increasingly being used for clinical diagnostics, with an impetus to expand reporting of incidental findings across a wide range of disorders. Analysis of population cohorts can help reduce risk for genetic variant misclassification and resultant unnecessary referrals to subspecialists. Objective: To examine the burden of candidate pathogenic variants for kidney and genitourinary disorders emerging from exome sequencing. Design: Secondary analysis of genetic data. Setting: A tertiary care academic medical center. Patients: A convenience sample of exome sequence data from 7974 self-declared healthy adults. Measurements: Assessment of the prevalence of candidate pathogenic variants in 625 genes associated with Mendelian kidney and genitourinary disorders. Results: Of all participants, 23.3% carried a candidate pathogenic variant, most of which were attributable to previously reported variants that had implausibly high allele frequencies. In particular, 25 genes (discovered before the creation of the Exome Aggregation Consortium, a genetic database comprising data from a large control population) accounted for 67.7% of persons with candidate pathogenic variants. After stringent filtering based on allele frequency, 1.4% of persons still had a candidate pathogenic variant, an excessive rate given the prevalence of monogenic kidney and genitourinary disorders. Manual annotation of a subset of variants showed that the majority would be classified as nonbenign under current guidelines for clinical sequence interpretation and could prompt subspecialty referrals if returned. Limitation: Limited access to health record data prevented comprehensive assessment of the phenotypic concordance with genetic diagnoses. Conclusion: Widespread reporting of incidental genetic findings related to kidney and genitourinary disorders will require stringent curation of clinical variant databases and detailed case-level review to avoid genetic misdiagnosis and unnecessary referrals. These findings motivate similar analyses for genes relevant to other medical subspecialties. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Human Genome Research Institute.

Carbamazepine drug reaction involving high fevers during the COVID-19 era.

Carbamazepine has demonstrated anticonvulsant properties and is used for a variety of indications in psychiatry and neurology. Total daily doses typically range from 200 to 1200 mg/d, generally divided into 2 doses. Carbamazepine has a broad side-effect profile but is not typically thought to produce high fevers in the absence of a hypersensitivity syndrome. This is a case of a probable adverse drug reaction to carbamazepine consisting of fever without severe major organ involvement. In this instance, a patient in a manic episode with psychotic features was briefly transferred to a COVID-19 unit to rule out coronavirus infection before the fever resolved.

Examining the relationship between gray matter volume and a continuous measure of bipolarity in unmedicated unipolar and bipolar depression.

BACKGROUND: It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals. METHODS: 158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p<0.001, family-wise error-corrected cluster-level p<0.05), with age, sex and total intracranial volume as covariates. RESULTS: GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone. LIMITATIONS: Incomplete clinical data required use of a modified BI scale. CONCLUSION: BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.

Patient Perspectives on Telepsychiatry on the Inpatient Psychiatric Unit During the COVID-19 Pandemic.

Hospitals have eliminated many in-person interactions and established new protocols to stem the spread of COVID-19. Inpatient psychiatric units face unique challenges, as patients cannot be isolated in their rooms and are at times unable to practice social distancing measures. Many institutions have experimented with providing some psychiatric services remotely to reduce the number of people physically present on the wards and decrease the risk of disease transmission. This case report presents 2 patient perspectives on receiving psychiatric care via videoconferencing while on the inpatient unit of a large academic tertiary care hospital. One patient identified some benefits to virtual treatment while the second found the experience impersonal; both were satisfied with the overall quality of care they received and were stable 2 weeks after discharge. These cases demonstrate that effective care can be provided remotely even to severely ill psychiatric patients who require hospitalization.

Interventions for posttraumatic stress disorder symptoms induced by medical events: A systematic review.

OBJECTIVE: Medical events such as myocardial infarction and cancer diagnosis can induce symptoms of posttraumatic stress disorder (PTSD). The optimal treatment of PTSD symptoms in this context is unknown. METHODS: A literature search of 6 biomedical electronic databases was conducted from database inception to November 2018. Studies were eligible if they used a randomized design and evaluated the effect of treatments on medical event-induced PTSD symptoms in adults. A random effects model was used to pool data when two or more comparable studies were available. RESULTS: Six trials met full inclusion criteria. Studies ranged in size from 21 to 81 patients, and included patients with PTSD induced by cardiac events, cancer, HIV, multiple sclerosis, and stem cell transplantation. All trials assessed psychological interventions. Two trials comparing a form of exposure-based cognitive behavioral therapy (CBT) with assessment-only control found that CBT resulted in lower PTSD symptoms [Hedges's g = -0.47, (95% CI -0.82 - -0.12), p = .009]. A third trial compared imaginal exposure (another form of exposure-based CBT) with an attention control and found a trend toward reduced PTSD symptoms. Three trials compared eye movement desensitization and reprocessing (EMDR) with active psychological treatments (imaginal exposure, conventional CBT, and relaxation therapy), and found that EMDR was more effective. CONCLUSION: CBT and EMDR may be promising approaches to reducing PTSD symptoms due to medical events. However, additional trials are needed in this patient population.

Early interventions to prevent posttraumatic stress disorder symptoms in survivors of life-threatening medical events: A systematic review.

Post-traumatic stress disorder (PTSD) induced by life-threatening medical events has been associated with adverse physical and mental health outcomes, but it is unclear whether early interventions to prevent the onset of PTSD after these events are efficacious. We conducted a systematic review to address this need. We searched six biomedical electronic databases from database inception to October 2018. Eligible studies used randomized designs, evaluated interventions initiated within 3 months of potentially traumatic medical events, included adult participants, and did not have high risk of bias. The 21 included studies (N = 4,486) assessed a heterogeneous set of interventions after critical illness (9), cancer diagnosis (8), heart disease (2), and cardiopulmonary surgery (2). Fourteen psychological, 2 pharmacological, and 5 other-type interventions were assessed. Four of the psychological interventions emphasizing cognitive behavioral therapy or meaning-making, 1 other-type palliative care intervention, and 1 pharmacological-only intervention (hydrocortisone administration) were efficacious at reducing PTSD symptoms relative to control. One early, in-hospital counseling intervention was less efficacious at lowering PTSD symptoms than an active control. Clinical and methodological heterogeneity prevented quantitative pooling of data. While several promising interventions were identified, strong evidence of efficacy for any specific early PTSD intervention after medical events is currently lacking.