... nurse educators across the country, who acknowledge an obligation to address the disparities that exist for underrepresented students at their schools of nursing, communicate a failure to ...acknowledge the differences that do exist for racial, ethnic, and gender-diverse students. ... I graduated at the top of my class with a 4.0 average, but never attended graduation. Noting that many were minority and ESL students, I proceeded to calculate which courses had the most minority student failures, which faculty members taught those courses, and the length of time those faculty members had been at our university.
Objective:
Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved ...by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.
Methods:
Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment.
Results:
At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.
Conclusions:
SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT’s durability and to compare it with other treatments.
Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study ...(GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 SNP2HLA; 0.939 HLA*IMP:02; 0.976 HIBAG). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations.
Fatal autoimmune myocarditis with rhabdomyolysis and refractory arrhythmias developed in two patients treated with a combination of anti–CTLA-4 and anti–PD-1 blockers. On histologic examination, a ...myocardial infiltrate suggested acute cardiac allograft rejection.
Immune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses.
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Ipilimumab, an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti–programmed death-1 (PD-1) antibody, have individually improved survival in patients with melanoma, and early results suggest that their combination further enhances antitumor activity and survival.
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Other adverse events associated with these agents include dermatitis, endocrinopathies, colitis, hepatitis, and pneumonitis, which are all thought to arise from aberrant activation of autoreactive T cells.
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These toxic effects are more frequent and severe when ipilimumab and nivolumab are used in combination.
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Here, we report . . .
Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele ...HLA‐B*15:02 is associated with an increased risk of Stevens–Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9 and/or HLA‐B genotypes (updates on cpicpgx.org).
The Undiagnosed Diseases Network, an NIH-funded network of seven U.S. sites, accepted 601 patients for evaluation over a 20-month period. Of the 382 patients who had a complete evaluation, 132 (35%) ...received a diagnosis; 15 of the diagnoses (11%) were made by clinical review alone and 98 (74%) by exome or genome sequencing.
HLA‐B35:01 and Green Tea–Induced Liver Injury Hoofnagle, Jay H.; Bonkovsky, Herbert L.; Phillips, Elizabeth J. ...
Hepatology (Baltimore, Md.),
June 2021, Volume:
73, Issue:
6
Journal Article
Peer reviewed
Open access
Background and Aims
Herbal supplements, and particularly multi‐ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated ...products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea‐associated liver injury.
Approach and Results
Among 1,414 patients enrolled in the U.S. Drug‐Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea–associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15‐448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re‐exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA‐B*35:01, found in 72% (95% confidence interval CI, 58‐87) of green tea cases, but only 15% (95% CI, 10‐20) caused by other supplements and 12% (95% CI, 10‐14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5‐11.5).
Conclusions
Green tea–related liver injury has distinctive clinical features and close association with HLA‐B*35:01, suggesting that it is idiosyncratic and immune mediated.
Discusses the Regular Education Initiative used to introduce students with mild mental retardation into classes with their peers for academic purposes. Seeks to provide unique alternatives and ...suggestions for the inclusion of students with mental retardation into groups with their peers. Offers a primary prevention model focusing on group interaction between members with special needs and regular education peers. (KW)
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