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991.
992.
Ahmed ElBoraie JulieAnne Tanner Andy Z.X. Zhu Katrina G. Claw Bhagwat Prasad Erin G. Schuetz Kenneth E. Thummel Koya Fukunaga Taisei Mushiroda Michiaki Kubo Neal L. Benowitz Caryn Lerman Rachel F. Tyndale 《CTS Clinical and Translational Science》2022,15(1):204
CYP2A6 activity, phenotyped by the nicotine metabolite ratio (NMR), is a predictor of several smoking behaviors, including cessation and smoking‐related disease risk. The heritability of the NMR is 60–80%, yet weighted genetic risk scores (wGRSs) based on common variants explain only 30–35%. Rare variants (minor allele frequency <1%) are hypothesized to explain some of this missing heritability. We present two targeted sequencing studies where rare protein‐coding variants are functionally characterized in vivo, in silico, and in vitro to examine this hypothesis. In a smoking cessation trial, 1687 individuals were sequenced; characterization measures included the in vivo NMR, in vitro protein expression, and metabolic activity measured from recombinant proteins. In a human liver bank, 312 human liver samples were sequenced; measures included RNA expression, protein expression, and metabolic activity from extracted liver tissue. In total, 38 of 47 rare coding variants identified were novel; characterizations ranged from gain‐of‐function to loss‐of‐function. On a population level, the portion of NMR variation explained by the rare coding variants was small (~1%). However, upon incorporation, the accuracy of the wGRS was improved for individuals with rare protein‐coding variants (i.e., the residuals were reduced), and approximately one‐third of these individuals (12/39) were re‐assigned from normal to slow metabolizer status. Rare coding variants can alter an individual’s CYP2A6 activity; their integration into wGRSs through precise functional characterization is necessary to accurately assess clinical outcomes and achieve precision medicine for all. Investigation into noncoding variants is warranted to further explain the missing heritability in the NMR. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
993.
Edward Compton Rachel Y. Goldstein Alexander Nazareth Stephen J. Shymon Lydia Andras Robert M. Kay 《Medicine》2022,101(2)
Previous studies demonstrated the safety of tranexamic acid (TXA) use in cerebral palsy (CP) patients undergoing proximal femoral varus derotational osteotomy (VDRO), but were underpowered to determine if TXA alters transfusion rates or estimated blood loss (EBL). The purpose of this study was to investigate if intraoperative TXA administration alters transfusion rates or EBL in patients with CP undergoing VDRO surgery.We conducted a retrospective review of 390 patients with CP who underwent VDRO surgery between January 2004 and August 2019 at a single institution. Patients without sufficient clinical data and patients with preexisting bleeding or coagulation disorders were excluded. Patients were divided into 2 groups: those who received intraoperative TXA and those who did not.Out of 390 patients (mean age 9.4 ± 3.8 years), 80 received intravenous TXA (TXA group) and 310 did not (No-TXA group). There was no difference in mean weight at surgery (P = .25), Gross Motor Function Classification System level (P = .99), American Society of Anesthesiologist classification (P = .50), preoperative feeding status (P = .16), operative time (P = .91), or number of procedures performed (P = .12) between the groups. The overall transfusion rate was lower in the TXA group (13.8%; 11/80) than the No-TXA group (25.2%; 78/310) (P = .04), as was the postoperative transfusion rate (7.5%; 6/80 in the TXA group vs 18.4%; 57/310 in the No-TXA group) (P = .02). The intraoperative transfusion rate was similar for the 2 groups (TXA: 7.5%; 6/80 vs No-TXA: 10.3%; 32/310; P = .53). The EBL was slightly lower in the TXA group, although this was not significant (TXA: 142.9 ± 113.1 mL vs No-TXA: 177.4 ± 169.1 mL; P = .09). The standard deviation for EBL was greater in the No-TXA group due to more high EBL outliers. The percentage of blood loss based on weight was similar between the groups (TXA: 9.2% vs No-TXA: 10.1%; P = .40). The number needed to treat (NNT) with TXA to avoid one peri-operative blood transfusion in this series was 9.The use of intraoperative TXA in patients with CP undergoing VDRO surgery lowers overall and postoperative transfusion rates.Level of evidence: III, Retrospective Comparative Study. 相似文献
994.
Glenn Waller Peter Slade Rachel Calam 《The International journal of eating disorders》1990,9(2):225-228
Clinicians have suggested that anorexic and bulimic disorders are associated with abnormal family interaction. This study used the FACES II questionnaire to test that hypothesis. Anorexic and bulimic women perceived their families as lower in adaptability (rigid) and cohesion (disengaged) than comparison women. However, there were no linear relationships between perceived family interaction and scores on the EAT-40. The FACES II is poorly associated with measures of eating attitudes but has a more clinically valid association with diagnosed eating disorders. 相似文献
995.
996.
Non-alcoholic fatty liver disease (NAFLD) is one of the most prominent causes of liver-related morbidity in the Western world. NAFLD is a chronic disease charac... 相似文献
997.
Rachel Rothschild H. Matthew Quitkin Frederic M. Quitkin Jonathan W. Stewart Katja Ocepek-Welikson Patrick J. McGrath Elaine Tricamo 《The International journal of eating disorders》1994,15(1):1-9
Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comor-bid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor ant/depressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size. © 1994 by John Wiley & Sons, Inc. 相似文献
998.
Mohsen Raza Ryan Geleit James Houston Rachel Williams Alex Trompeter 《The British journal of radiology》2021,94(1125)
Objectives:Orthopaedic surgeons have a responsibility to minimise risks of ionising radiation to patients, themselves and staff. This study aims to establish the understanding of radiation practice, legislation and risk by orthopaedic surgeons.Methods:A nationwide online survey of UK-based orthopaedic surgeons was conducted. Participants answered 18 multiple-choice questions assessing level of radiation safety training, basic principles/knowledge of ionising radiation, relevant legislation and operating practice.Results:A total of 406 surgeons completed the survey. 92% reported using intraoperative ionising radiation at least once per week. 38% received no formal training on radiation safety. Knowledge of basic principles of radiation and legislation was limited. There was variable knowledge when labelling an image intensifier machine and choosing its safest orientation. Poor uptake of radiation protection equipment was noted. Only 19% agreed they had adequate training in ionising radiation safety and 27% reported receiving adequate training in equipment emitting ionising radiation in the operating theatre.Conclusion:Many orthopaedic surgeons in the UK do not believe they are adequately trained in radiation safety. There is a deficiency amongst practicing surgeons in basic knowledge, relevant legislation and practicalities of the use of ionising radiation in the operating room. This could potentially put patients and health-care professionals at additional risk. We recommend that a standardised national training programme on the basic principles and safety of ionising radiation is implemented for all practicing orthopaedic surgeons.Advances in knowledge:This paper is the first UK national survey amongst orthopaedic surgeons and is one of the largest reported internationally. 相似文献
999.
1000.
Rachel Hennein Petty Tineo Jessica Bonumwezi Hannah Gorman Max Jordan Nguemeni Tiako Sarah R. Lowe 《Journal of general internal medicine》2022,37(6):1475
BackgroundRacial and ethnic diversity of healthcare workers have benefits on team functioning and patient care. However, a significant barrier to retaining diverse providers is discrimination.ObjectiveTo assess the predictors, perpetrators, and narratives of racial discrimination among healthcare workers.DesignSurvey study.ParticipantsHealthcare workers employed at academic hospitals.Main MeasuresWe assessed prevalence and perpetrators of racial and ethnic discrimination using the General Ethnic Discrimination Scale. We included an open-ended question asking respondents to recount experiences of discrimination and analyzed responses using grounded theory.Key ResultsOf the 997 participants, 12.2% were females from backgrounds underrepresented in medicine (URM), 4.0% URM males, 10.1% Asian females, 4.7% Asian males, 49.1% non-Hispanic White females, and 19.8% non-Hispanic White males. Among healthcare workers of color, 85.2% reported discrimination. Over half of URM females (51.4%), URM males (52.6%), and Asian females (62.5%) reported discrimination by patients. About 20–25% of URM females, URM males, and Asian females reported discrimination by teachers, supervisors, co-workers, and institutions. In adjusted binary logistic models, URM females had 10.14 odds (95% confidence interval [95%CI]: 5.13, 20.02, p<.001), URM males 6.23 odds (95%CI: 2.59, 14.98, p<.001), Asian females 7.90 odds (95%CI: 4.07, 15.33, p<.001), and Asian males 2.96 odds (95% CI: 1.47, 5.97, p=.002) of reporting discrimination compared with non-Hispanic White males. Needing more support was associated with 2.51 odds (95%CI: 1.54, 4.08, p<.001) of reporting discrimination. Our qualitative findings identified that the murder of George Floyd intensified URM healthcare workers’ experiences of discrimination through increased fear of violence and requests for unpaid diversity work. Asian healthcare workers reported that pandemic-related anti-Asian violence shaped their experiences of discrimination through increased fear of violence and care refusal from patients.ConclusionsOur findings provide insights into experienced discrimination among healthcare workers and opportunities for hospitals to create programs that improve inclusivity.KEY WORDS: discrimination, race and ethnicity, bias, healthcare workers 相似文献