Key Articles and Guidelines Relative to Intensive Care Unit Pharmacology—2004

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90189/1/phco.25.4.585.61024.pd

Key Articles and Guidelines Relative to Intensive Care Unit Pharmacotherapy: 2009 Update

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90162/1/phco.29.10.1228.pd

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Copyright, Ownership, and Digital Media: A Trilogy

Book review: FREE CULTURE: HOW BIG MEDIA USES TECHNOLOGY AND THE LAW TO LOCK DOWN CULTURE AND CONTROL CREATIVITY. By Lawrence Lessig. 2004. New York, N.Y.: Penguin Press. Pp. xiii, 386. Reviewed by Jessica L. Reyman. Book review: PROMISES TO KEEP: TECHNOLOGY, LAW, AND THE FUTURE OF ENTERTAINMENT. By William W. Fisher III. Stanford, Cal.: Stanford University Press. Pp. ix, 340. Reviewed by Gretchen Haas. Book review: THE ANARCHIST IN THE LIBRARY: HOW THE CLASH BETWEEN FREEDOM AND CONTROL IS HACKING THE REAL WORLD AND CRASHING THE SYSTEM. By Siva Vaidhyanathan. 2004. New York, N.Y.: Basic Books. Pp. ix, 256. Reviewed by Laurie A. Johnson & Krista A. Kennedy

Functional Outcomes From Psychotherapy for People With Posttraumatic Stress Disorder: A Meta-Analysis

People with posttraumatic stress disorder (PTSD) experience a wide array of symptoms, often accompanied by significant functional and quality of life impairments. Evidence-based psychotherapies are effective for alleviating symptoms in this group, but functional outcomes following psychotherapy are understudied. This study aimed to synthesize existing work on functional outcomes of psychotherapy to conduct a meta-analytic investigation examining whether people with PTSD experience significant improvements in functioning and quality of life following a course of psychotherapy. A literature search was conducted for studies reporting results of randomized clinical trials of psychotherapies for people diagnosed with PTSD that included a functional or quality of life outcome measured at pre- and post-intervention. Both between-groups and within-groups analyses were conducted using a random effects model. Fifty-six independent samples were included. Results suggest that, on average, people with PTSD experience significant, moderate improvement in functional outcomes after a course of psychotherapy. Taken together, this meta-analysis represents a substantial advance in our understanding of functional outcomes of psychotherapy for people with PTSD. Findings suggest that psychotherapy is one vehicle through which functional outcomes may be improved for this group, though notably to a lesser degree than symptom improvement

Sleep Disorders In Veterans With Serious Mental Illnesses: Prevalence In VA Health Record Data

Study Objectives:: This study aimed to estimate the 12-month prevalence of diagnosed sleep disorders among veterans with and without serious mental illnesses (SMI) in VA health record data in 2019. We also examined diagnosed sleep disorders across a 9-year period and explored associations with demographic and health factors. Methods:: This study used health record data from VISN 4 of the Veterans Health Administration (VHA) from 2011-2019. SMI diagnoses included schizophrenia and bipolar spectrum diagnoses as well as major depression with psychosis. Sleep diagnoses included insomnias, hypersomnias, sleep-related breathing disorders, circadian rhythm sleep-wake disorders, and sleep-related movement disorders. Demographic and health-related factors were also collected from the record. Results:: In 2019, 21.8% of veterans with SMI were diagnosed with a sleep disorder. This is a significantly higher proportion than for veterans without SMI, 15.1% of whom were diagnosed with a sleep disorder. Sleep disorder rates were highest in veterans with a chart diagnosis of major depression with psychosis. From 2011 to 2019, the overall prevalence of sleep disorders in veterans with SMI more than doubled (10.2% to 21.8%), suggesting improvements in the detection and diagnosis of sleep concerns for this group. Conclusions:: Our findings suggest that identification and diagnosis of sleep disorders for veterans with SMI has improved over the past decade, though diagnoses still likely underrepresent actual prevalence of clinically relevant sleep concerns. Sleep concerns may be at particularly high risk of going untreated in veterans with schizophrenia-spectrum disorders