Retrotransposon Tf1 is targeted to Pol II promoters by transcription activators.

The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration.

Understanding the association between admission source and in-hospital delirium: A cross-sectional study.

Patients admitted via interhospital transfer (IHT) experience increased risk-adjusted mortality, adverse events, length of stay, and discharge to facility; however, the etiology is not well understood. We hypothesize that IHTs are more likely to experience in-hospital delirium as compared with admissions to the hospital via the emergency department (ED) and clinic. This is a cross-sectional study of all adult admissions to medical, surgical, neurological, and obstetrics and gynecology services at an academic medical center who were screened for delirium between August 2018 and January 2020. Unit of analysis was admission source (IHT vs ED vs clinic) as the independent variable and the primary outcome was in-hospital delirium, assessed with initial brief confusion assessment method (bCAM) screening. 30,100 hospitalizations were included in this study with 3925 admissions (13.0%) screening positive for delirium at the initial bCAM assessment. The prevalence of delirium was much higher in IHTs at 22.3% (1334/5971) when compared with clinic at 5.8% (244/4214) and ED at 11.8% (2347/19,915) admissions. Multivariable logistic regression adjusting for demographics and comorbidities showed that IHT admissions had higher odds (OR 1.91, 95% CI 1.74 to 2.10) and clinic admissions had lower odds (OR 0.56, 95% CI 0.48 to 0.64) of in-hospital delirium compared with ED admissions. Increased odds of delirium in IHT admissions may contribute to the observed increased length of stay, discharge to facility, and mortality. These results emphasize the importance of routine screening and possible intervention prior to patient transfer.

Development and Assessment of Simulation-Based Point-of-Care Ultrasound Curriculum in Undergraduate Medical Education.

OBJECTIVES: Implementation barriers and lack of standardized point-of-care ultrasound (POCUS) curricula make the development of effective POCUS curricula and methods of assessment challenging. The authors aim to develop a longitudinal POCUS curriculum through staged intervention. In the first stage, the authors hypothesized that the use of high-fidelity ultrasound simulation during the Internal Medicine clerkship would improve POCUS confidence and knowledge among medical students, minimizing the need for trained faculty. METHODS: A quasi-experimental study of third-year students on the Internal Medicine clerkship at a large academic medical center in the United States was performed assessing the efficacy of ultrasound simulation use. The control group consisted of students who received baseline POCUS education during teaching rounds but did not have access to the ultrasound simulator. The experimental group consisted of students who, in addition to baseline POCUS education, had access to a high-fidelity ultrasound simulator throughout the clerkship for a minimum of 1 hour per week. Students in both the control and experimental groups completed a pre- and post-intervention confidence survey and knowledge-based examination. RESULTS: Eighty-two percent (50/61) of students completed pre- and post-tests, with the control group demonstrating no significant difference in POCUS confidence or knowledge. After exposure to the ultrasound simulator, the experimental group demonstrated statistically significant improvement in POCUS confidence and overall POCUS knowledge (p < .01). CONCLUSION: The use of high-fidelity ultrasound simulation can improve POCUS confidence and knowledge among medical students while addressing common barriers to the implementation of a POCUS curriculum. Despite showing statistically significant improvement in overall knowledge, the results did not appear to hold educational significance. Additional POCUS educational methods are necessary to overcome cognitive bias and potential overconfidence. The next stage of curriculum development will include resident-led POCUS workshops to supplement simulation.

Patient perception of obesity versus physician documentation of obesity: A quality improvement study.

As the prevalence of obesity increases, the prevalence of associated comorbid diseases, obesity-related mortality rates and healthcare costs rise concordantly. Two main factors that hinder efforts to treat obesity include a lack of recognition by patients and documentation by physicians. This study evaluates the relationship between patient perception of obese weight and physician documentation of obesity. This quality improvement observational study surveyed patients of an academic internal medicine clinic on their perception of obesity. Responses were compared to longitudinal physician documentation of obesity and body mass index (BMI). A total of 59.9% of patients with obesity perceived their weight as obese. While 33.7% of patients with a BMI of 30 to 34.9 kg/m2 perceived themselves as having obesity, 71.4% of patients with a BMI of 45 to 49.9 kg/m2 perceived themselves as having obesity. A total of 42.4% of patients with obesity had physician documentation of obesity in the last year. While 25% of patients with a BMI of 30 to 34.9 kg/m2 had physician documentation of obesity, 85.7% of patients with a BMI of 45 to 49.9 kg/m2 had physician documentation of obesity. For patients with a BMI ≥50 kg/m2 , 52.9% perceived their weight to be obese and 76.5% had physician documentation of obesity in the last year. Both patient perception and physician documentation of obesity were significantly less than the prevalence of obesity. Patient perception of obesity and provider documentation of obesity increased as BMI increased until a BMI ≥50 kg/m2 . Both patients and providers must improve recognition of this disease.

When Do Clinicians Follow-up Abnormal Liver Tests in Primary Care?

BACKGROUND: Many guidelines addressing the approach to abnormal liver chemistries, including bilirubin, transaminases and alkaline phosphatase, recommend repeating the tests. However, when clinicians repeat testing is unknown. MATERIAL AND METHODS: This retrospective study followed adult patients with abnormal liver chemistries in a patient-centered medical home (PCMH) from 2007 to 2016. All PCMH patients possessing at least 1 abnormal liver test (total bilirubin, aminotransferases and alkaline phosphatase) were included. Patients were followed from the index abnormal liver chemistry until the next liver test result, or the end of the study period. The primary predictor variable of interest was the number of abnormal chemistries (out of 4) on index testing. Demographic and clinical variables served as other potential predictors of outcome. A Cox proportional hazards model was applied to investigate associations between the predictor variables and the time to repeat liver chemistry testing. RESULTS: Of 9,545 patients with at least 2 PCMH visits and 1 liver test abnormality, 6,489 (68%) obtained repeat testing within 1 year, and 80% of patients had follow-up tests within 2 years. Patients with multiple abnormal liver tests and those with higher degrees of abnormality were associated with shorter time to repeat testing. CONCLUSIONS: A large proportion of patients with abnormal liver tests still lack repeat testing at 1 year. The number of liver abnormal liver tests and degree of elevation were inversely associated with the time to repeat testing.

Assessing the Burden of Abnormal LFTs and the Role of the Electronic Health Record: A Retrospective Study.

BACKGROUND: Primary care clinicians encounter abnormal liver function tests (LFTs) frequently. This study assesses the prevalence of abnormal LFTs and patient follow-up patterns in response. METHODS: This is a retrospective study from 2007-2016 of adult patients with abnormal LFTs seen in an internal medicine clinic. The proportion of patients with follow-up testing and the time (in days) to repeat LFTs were the primary outcomes measured. Results were evaluated before and after the implementation of the institution's electronic health record (EHR). RESULTS: This study identified a period prevalence for abnormal LFTs of 39%. Of these, 9,545 unique patients met inclusion criteria, with 8,415 patients (88.2%) possessing follow-up LFTs and no significant difference in the proportion of patients receiving follow-up by degree of initial abnormality. Median time to follow-up in mild abnormalities (1-2 times normal) was 138 days, compared to 21 days for severe abnormalities (>4 times normal, P < 0.0001). Reduced time to repeat testing across all spectrums of abnormality was observed following EHR implementation, but proportions of missing follow-up did not improve. A multivariable logistic regression model identified younger age, poverty, living over 50 miles from clinic, recent cohort entry and a lower magnitude of abnormality as predictors for missing repeat LFT testing (area under the curve = 0.838 [95% CI: 0.827-0.849]). CONCLUSIONS: Abnormal LFTs were detected in 39% of all patients seen. The degree of LFT abnormality did not influence rates of follow-up testing, but does appear to play a role in the timing of repeat testing, when obtained. Follow-up rates did not improve with EHR implementation.

Evaluation of liver test abnormalities in a patient-centered medical home: do liver test patterns matter?

Abnormal liver tests are extremely common in clinical practice, present with varying patterns and degrees of elevation, and can signal liver injury from a variety of causes. Responding to these abnormalities requires complex medical decision-making and merits investigation in primary care. This retrospective study investigates the association of patterns of liver test abnormality with follow-up in primary care. Using administrative data, this study includes patients with abnormal liver tests seen between 2007 and 2016 in a patient-centered medical home. Liver tests examined include serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients entered the cohort on the first liver test elevation. The outcome examined was completion of repeat testing, and the proportions of patients without follow-up were compared by patterns of index abnormality. 9545 patients met the inclusion criteria. Of these, 6155 (64.5%) possessed one liver test abnormality and 3390 (35.5%) possessed multiple abnormalities on index testing. Overall 1119 (11.7%) patients did not have repeat testing performed during the study period. A greater proportion of patients with lone abnormalities lacked repeat testing compared with those patients with multiple abnormalities. Differences in repeat testing appeared when comparing clinical patterns of abnormality, with higher proportions of follow-up in patients with testing suggestive of cholestasis. Over 11% of patients with abnormal liver tests did not undergo repeat testing during the study period. Repeat testing occurred more often in patients with multiple abnormalities and in clinical patterns suggestive of cholestasis. This study highlights a potential opportunity to improve quality of care.