Contrasting Perspectives of Anesthesiologists and Gastroenterologists on the Optimal Time Interval between Bowel Preparation and Endoscopic Sedation

Background. The optimal time interval between the last ingestion of bowel prep and sedation for colonoscopy remains controversial, despite guidelines that sedation can be administered 2 hours after consumption of clear liquids. Objective. To determine current practice patterns among anesthesiologists and gastroenterologists regarding the optimal time interval for sedation after last ingestion of bowel prep and to understand the rationale underlying their beliefs. Design. Questionnaire survey of anesthesiologists and gastroenterologists in the USA. The questions were focused on the preferred time interval of endoscopy after a polyethylene glycol based preparation in routine cases and select conditions. Results. Responses were received from 109 anesthesiologists and 112 gastroenterologists. 96% of anesthesiologists recommended waiting longer than 2 hours until sedation, in contrast to only 26% of gastroenterologists. The main reason for waiting >2 hours was that PEG was not considered a clear liquid. Most anesthesiologists, but not gastroenterologists, waited longer in patients with history of diabetes or reflux. Conclusions. Anesthesiologists and gastroenterologists do not agree on the optimal interval for sedation after last drink of bowel prep. Most anesthesiologists prefer to wait longer than the recommended 2 hours for clear liquids. The data suggest a need for clearer guidelines on this issue

A Novel Phenotype-Based Drug-Induced Liver Injury Causality Assessment Tool (DILI-CAT) Allows for Signal Confirmation in Early Drug Development

ECU/Wiley Open Access Read-and-Publish agreemen

Amoxicillin-Clavulanate-Induced Liver Injury

Background and Aims Amoxicillin–clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Methods Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. Results One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. Conclusion AC-DILI causes a moderately severe, mixed hepatocellular–cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation

U.S. Physician-Scientist Workforce in the 21st Century: Recommendations to Attract and Sustain the Pipeline

The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort. It is through biomedical research that certain diseases have been eliminated, cures for others have been discovered, and medical procedures and therapies that save lives have been developed. Yet, the U.S. PS workforce has both declined and aged over the last several years. The resulting decreased inflow and outflow to the PS pipeline renders the system vulnerable to collapsing suddenly as the senior workforce retires. In November 2015, the Alliance for Academic Internal Medicine hosted a consensus conference on the PS workforce to address issues impacting academic medical schools, with input from early-career PSs based on their individual experiences and concerns. One of the goals of the conference was to identify current impediments in attracting and supporting PSs and to develop a new set of recommendations for sustaining the PS workforce in 2016 and beyond. This Perspective reports on the opportunities and factors identified at the conference and presents five recommendations designed to increase entry into the PS pipeline and nine recommendations designed to decrease attrition from the PS workflow

Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug‐Induced Liver Injury Network (DILIN)

Background & AimsBecause of the lack of objective tests to diagnose drug‐induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test–retest reliability is unknown. To determine the test–retest reliability of the expert opinion process used by the Drug‐Induced Liver Injury Network (DILIN).MethodsThree DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow‐up information. One hundred randomly selected DILIN cases were re‐assessed using the same processes for initial assessment but by three different reviewers in 92% of cases.ResultsThe median time between assessments was 938 days (range 140–2352). Thirty‐one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50–0.71) and 0.60 (0.52–0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury.ConclusionsThe DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as ≥50% likely to be DILI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111130/1/liv12540.pd

Drug-induced liver injury in the elderly: Consensus statements and recommendations from the IQ-DILI Initiative

The elderly demographic is the fastest-growing segment of the world\u27s population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) that encourage data collection in the elderly and recommend improved practices that will facilitate a more inclusive approach. To establish what is already known about DILI in the elderly and pinpoint key gaps of knowledge in this arena, a working definition of elderly is required that accounts for both chronologic and biologic ages and varying states of frailty. In addition, it is critical to characterize the biological role of aging on liver function, as well as the different epidemiological factors such as polypharmacy and inappropriate prescribing that are common practices. While data may not show that elderly people are more susceptible to DILI, DILI due to specific drugs might be more common in this population. Improved characterization of DILI in the elderly may enhance diagnostic and prognostic capabilities and improve the way in which liver safety is monitored during clinical trials. This summary of the published literature provides a framework to understand and evaluate the risk of DILI in the elderly. Consensus statements and recommendations can help to optimize medical care and catalyze collaborations between academic clinicians, drug manufacturers, and regulatory scientists to enable the generation of high-quality research data relevant to the elderly population

Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.</p> <p>Methods</p> <p>Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.</p> <p>Results</p> <p>Seven individual protein spots were identified as either significantly increased (α₂-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α₂-macroglobulin, are included in existing non-invasive serum marker panels.</p> <p>Conclusion</p> <p>Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.</p

1965: Abilene Christian College Bible Lectures - Full Text

LIFT UP YOUR EYES” Being the Abilene Christian College Annual Bible Lectures 1965 Price: $3.95 Published by ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE ACC Station Abilene. Texa