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Background & Aims: Liver transplantation is the only treatment that increases survival times of patients with decompensated cirrhosis. Patients who live farther away from a transplant center are disadvantaged. Health care delivery via telehealth is an effective way to manage patients with decompensated cirrhosis remotely. We investigated the effects of telehealth on the liver transplant evaluation process., Methods: We performed a retrospective study of 465 patients who underwent evaluation for liver transplantation at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Of these, 232 patients were evaluated via telehealth, and 233 via in-person evaluation. Using regression models, we evaluated the differential effects of telehealth vs usual care on placement on the liver transplant waitlist. We also investigated the effects of telehealth on time from referral to initial evaluation by a transplant hepatologist, liver transplantation, and mortality., Results: Patients in the telehealth group were evaluated significantly faster than patients evaluated in person, without or with adjustment for potential confounders (21.7 vs 79.5 d; P < .01). Telehealth also was associated with a significantly shorter time on the liver transplant waitlist (138.8 vs 249 d; P < .01). After propensity-matched analysis, telehealth was associated with a reduction in the time from referral to evaluation (hazard ratio, 0.15; 95% CI, 0.09-0.21; P < .01) and listing (hazard ratio, 0.26; 95% CI, 0.12-0.40; P < .01), but not to transplantation. In the intent-to-treat analysis of all referred patients, we found no significant difference in pretransplant mortality between patients evaluated via telehealth vs in-person. There was statistically significant interaction between model for end-stage liver disease (MELD)-Na scores and time to evaluation (P = .009) and placement on the transplant waitlist (P = .002), with telehealth offering greater benefits to patients with low MELD-Na scores., Conclusions: Use of telehealth is associated with a substantial reduction in time from referral to initial evaluation by a hepatologist and placement on the liver transplant waitlist, especially for patients with low MELD scores, with no changes in time to transplantation or pretransplant mortality. More studies are needed, particularly outside of the Veterans Administration Health System, to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Killer immunoglobulin-like receptor (KIR) and KIR ligand (KIRL) interactions play an important role in natural killer (NK) cell-mediated graft-versus-leukemia effect following hematopoietic cell transplantation (HCT). However, there is considerable heterogeneity in the KIR gene and KIRL content in individuals, making it difficult to estimate the full clinical impact of NK cell reconstitution following HCT. Here we present a novel adaptive mathematical model designed to quantify these interactions to better assess the influence of NK cell-mediated alloreactivity on transplant outcomes. Ninety-eight HLA- matched unrelated donor (URD) HCT recipients were studied retrospectively. The KIR-KIRL interactions were quantified using a system of matrix equations. Unit values were ascribed to each KIR-KIRL interaction, and the directionality of interactions was denoted by either a positive (activating) or negative (inhibition) symbol; these interactions were then summed. The absolute values of both the missing KIRL and inhibitory KIR-KIRL interactions were significantly associated with overall survival and relapse. These score components were initially used to develop a weighted score (w-KIR score) and subsequently a simplified, nonweighted KIR-KIRL interaction score (IM-KIR score). Increased w-KIR score and IM-KIR score were predictive of all-cause mortality and relapse (w-KIR score: hazard ratio [HR], .37 [P = .001] and .44 [P = .044], respectively; IM-KIR score: HR, .5 [P = .049] and .44 [P = .002], respectively). IM-KIR score was also associated with NK cell reconstitution post-HCT. KIR-KIRL interactions as reflected by the w-KIR and IM-KIR scores influence both relapse risk and survival in recipients of HLA-matched URD HCT with hematologic malignancies., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to declare., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background Medical training relies on direct observations and formative feedback. After residency graduation, opportunities to receive feedback on clinical teaching diminish. Although feedback through learner evaluations is common, these evaluations can be untimely, non-specific, and potentially biased. On the other hand, peer feedback in a small group setting or lecture format has been shown to be beneficial to teaching behaviors, however, little is known if peer observation using a standardized tool followed by feedback results in improved teaching behaviors. Therefore, the objective of this study was to examine if feedback after peer observation results in improved inpatient teaching behaviors. Methods This study was conducted at a tertiary care hospital. Academic hospitalists in the Division of Hospital Medicine developed a standardized 28-item peer observation tool based on the Stanford Faculty Development Program to observe their peers during bedside teaching rounds and provide timely feedback after observation. The tool focused on five teaching domains (learning climate, control of session, promotion of understanding and retention, evaluation, and feedback) relevant to the inpatient teaching environment. Teaching hospitalists were observed at the beginning of a two-week teaching rotation, given feedback, and then observed at the end of the rotation. Furthermore, we utilized a post-observation survey to assess the teaching and observing hospitalists' comfort with observation and the usefulness of the feedback. We used mixed linear models with crossed design to account for correlations between the observations. Models were adjusted for gender, age, and years of experience. We tested the internal validity of the instrument with Cronbach's alpha. Results Seventy (range: one to four observations per faculty) observations were performed involving 27 teaching attendings. A high proportion of teachers were comfortable with the observation (79%) and found the feedback helpful (92%), and useful for their own teaching (88%). Mean scores in teaching behavior domains ranged from 2.1 to 2.7. In unadjusted and adjusted analysis, each teaching observation was followed by higher scores in learning climate (adjusted improvement = 0.09; 95% CI = 0.02-0.15; p = 0.007) and promotion of understanding and retention (adjusted improvement = 0.09; 95% CI = 0.02-0.17; p = 0.01). The standardized observation tool had Cronbach's alpha of 0.81 showing high internal validity. Conclusions Peer observation of bedside teaching followed by feedback using a standardized tool is feasible and results in measured improvements in desirable teaching behaviors. The success of this approach resulted in the expansion of peer observation to other Divisions within the Department of Internal Medicine at our Institution., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Pedram et al.)

Rationale: Ineffective peak inspiratory flow rate (PIFR) generation in patients using inhalers results in insufficient drug delivery to the lungs and poor clinical outcomes. Low inspiratory muscle strength is associated with suboptimal PIFR., Objective: To examine in a prospective study the relationship between PIFR and skeletal muscle strength using hand grip strength (HGS) as a surrogate., Methods: Adult patients admitted with acute exacerbation of chronic obstructive pulmonary disease (COPD) were enrolled. PIFR was measured within 48 hours before discharge. PIFR below 60L/min was considered suboptimal. HGS was measured using a handheld dynamometer. Any readmissions and emergency department visit data were collected. The associations between PIFR, HGS, 30 and 90-day COPD and all-cause readmissions were examined, without and with adjustment for age, race and gender., Results: Of the 75 enrolled patients, 56% had suboptimal PIFR; they were older (63.9±9.7 vs. 58.2±7.7 years) and had significantly lower HGS (24.2±11.1 vs. 30.9±10.9 Kg) compared to those with optimal PIFR. There were no significant differences between the two PIFR groups by gender, race, history of coronary artery disease, congestive heart failure, hypertension or functional scores. Each kilogram increase in HGS was associated with 0.50 (95%CI 0.18-0.89, p = 0.003) L/min increase in PIFR. We did not observe an association between PIFR and 30 or 90-day readmission rates., Conclusion: We found a significant association between HGS and PIFR in hospitalized patients with acute exacerbations of COPD. Whether interventions aimed at increasing skeletal muscle strength also result in improvement in PIFR remains unclear and need further study., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Prior studies have reported the adverse effects of strain on patient outcomes. There is a paucity of literature about a type of strain that may be caused by near-simultaneous intensive care unit (ICU) admissions. We hypothesized that when multiple admissions arrive nearly at the same time, the ICU teams are excessively strained, and this leads to unfavorable patient outcomes., Methods: This is a retrospective cohort study of consecutive adult patients admitted to an academic medical ICU of a tertiary referral center over five consecutive years. Primary outcomes were the all-cause hospital and ICU mortality., Results: We enrolled 13,234 consecutive ICU admissions during the study period. One-fourth of the admissions had an elapsed time since the last admission (ETLA) of < 55 min. Near-simultaneous admissions (NSA) had on average, a higher unadjusted odds ratio (OR) of ICU death of 1.16 (95% CI 1-1.35, P = 0.05), adjusted 1.23 (95% CI 1.04-1.44, P = 0.01), unadjusted hospital death of 1.11 (95% CI 0.99-1.24, P = 0.06), adjusted 1.20 (95% 1.05-1.35, P = 0.004), and a lower adjusted OR of home discharge of 0.91 (95% CI 0.84-0.99, P = 0.04). NSA was associated with 0.16 (95% CI 0.04-0.29, P = 0.01) added days in the ICU. For each incremental unit increase of the logarithmic transformation of ETLA [log (ETLA in minutes)], the average adjusted hospital mortality OR incrementally decreased by an added average OR of 0.93 (95% CI 0.89‒0.97, P = 0.001)., Conclusion: Our results suggest that near-simultaneous ICU admissions (NSA) are frequent and are associated with a dose-dependent effect on mortality, length of stay, and odds of home versus nursing facility discharge.

Rationale: Although the Hospital Readmission Reduction Program (HRRP) has reduced the 30-day readmission rates for patients with chronic obstructive pulmonary disease (COPD) across hospitals, the effect of HRRP on hospital mortality remains unknown. Therefore, we examined the association between hospital readmissions and mortality rates for patients discharged with acute exacerbation of COPD (AECOPD)., Method: The all-cause hospital-specific 30-day risk-standardized mortality rate (RSMR) and the 30-day risk-standardized readmission rate (RSRR) for patients with COPD from 2010 to 2017 were obtained from the Hospital Compare website. Hospital service area (HSA) information was obtained from the Dartmouth Atlas of Healthcare. The longitudinal relationship between the mortality and readmission rates of a hospital was assessed using mixed linear models., Results: Of the 3,685 hospitals analyzed, the unadjusted mean RSMRs increased from 7.8% to 8.4% during the study period at a yearly rate of 0.13 (95% CI = 0.12 to 0.14; P < .001), whereas the mean RSRRs declined from 20.7% to 19.6%. When examined according to the baseline readmission rate and interaction with time, each 1% higher-than-baseline readmission rate was associated with a smaller increase in mortality rate by 0.015% (95% CI = -0.02 to -0.01; P < .0001). Inclusion of change in readmissions in the model showed that each 1% decrease in readmission rate was associated with 0.04% (95% CI = -0.01 to -0.06; P = .008) increase in mortality., Conclusion: This hospital-level analysis of AECOPD showed that although the 30-day all-cause readmission rates declined, the mortality rates increased. Hospitals with lower readmission rates had higher mortality rates over time.

While serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with all-cause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999-2004). We used survey weight-adjusted linear regression to examine the association between AMH and CRP without and with adjustment for age, race, body mass index (BMI), smoking, hypertension, diabetes, cholesterol, glomerular filtration rate (GFR), testosterone, androstenedione, and sex hormone binding globulin. Of the 949 men, 212 (22%) were elderly, 493 (52%) Caucasian, 254 (27%) current smokers, 100 (10%) diabetics, and 312 (33%) had hypertension. Mean (SD) AMH was 8.4 (7.2) ng/mL and median (IQR) CRP level was 0.17 (3) mg/L. Using linear regression, each 10 ng/mL rise in AMH was associated with 0.09 mg/dL (95%CI = -0.14 to -0.03; p = 0.002) decrease before and 0.08 mg/dL (95%CI = -0.13 to -0.02; p = 0.004) decrease in CRP after adjusting for potential confounders. Similarly, men in the highest quartile of AMH had significantly lower CRP compared to those in the lowest quartile (unadjusted difference = -0.19 mg/dL; 95%CI = -0.31 to -0.06; p = 0.006, adjusted difference = -0.16 mg/dL; 95%CI = -0.3 to -0.01; p = 0.035). We found an independent, robust, and inverse association between CRP and AMH in men. Effect of AMH on mortality may be through amelioration of inflammation.

Objective The purpose of this study was to assess the association between the psychological well-being and satisfaction of patients with physicians during their hospitalization. Methods This cross-sectional study was conducted at a local hospital using the following surveys: Brief Inventory of Thriving (BIT), tool to assess inpatient satisfaction with care from hospitalists (TAISCH) survey, and Erlanger Internal Patient satisfaction survey addressing demographic questions and questions on physicians' quality of care and etiquette. Mixed linear regression models were created to examine the effect of psychological well-being on patient satisfaction. Models were adjusted for age, race, and gender, and all analyses were performed in R 3.1.1 using the 'lme4' package with statistical significance set at p<0.05. Results A total of 360 patients were enrolled in this analysis and the mean age of the cohort was 54.5 years. In the unadjusted analysis, each unit increase in BIT score was associated with a 0.3% (95% CI:0.19-0.4, p<0.001) increase in mean satisfaction score using the five-domain questionnaire and a 0.25% (95%CI:0.16-0.34, p<0.01) increase in mean satisfaction score using the TAISCH questionnaire. Multivariable models, after adjusting confounding variables, also showed the direct and statistically significant relationship between patients' level of psychological well-being and patient satisfaction. Each unit increase in BIT score was associated with a 0.31% (95% CI:0.20-0.43, p<0.001) and 0.26% (95% CI:0.17-0.36, p<0.001) increase in mean satisfaction scores across the five-domain questionnaire and TAISCH questionnaire. Conclusions There is a positive correlation between the level of patients' psychological well-being and satisfaction with his/her physician with a statistical significance. With patient-specific strategies, we can further improve patient rapport with their physicians, resulting in positive patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

Aims: The small number of studies that have investigated the relationship between serum vitamin D levels and cardiorespiratory fitness (CRF) have reported conflicting results. We investigated the association between vitamin D levels and CRF in a representative sample of the US population using data from the National Health and Nutrition Survey (2001-2004)., Methods: We included participants between the ages of 20 and 49 years and excluded those with vitamin D levels at the 5% extremes of the distribution. We used survey-weighted linear regression without and with adjustment for age, sex, race, body mass index, hypertension, diabetes, smoking, C-reactive protein, hemoglobin, and glomerular filtration rate to examine the relationship between the maximal oxygen consumption (VO 2 max) (as a surrogate for CRF) and vitamin D levels., Results: Of the 1995 participants, 45.2% were women, 49.1% were white, 13% had hypertension, and 4% had diabetes. The mean ± SD age was 33 ± 8.6 years, with a mean ± SD vitamin D level of 58 ± 5.3 nmol/L and a mean ± SD VO 2 max of 40 ± 9.7 ml/kg/min. Participants in the highest quartile of vitamin D levels had a significantly higher CRF than participants in the lowest quartile (difference 4.3, 95% confidence interval (CI) 3.0-5.5; P < 0.001). After adjustment for potential confounders, the difference between the highest and lowest vitamin D quartiles remained significant (difference 2.9, 95% CI 1.6-4.1; P < 0.001). In unadjusted and adjusted linear regression, each 10 nmol/L increase in vitamin D level was associated with a significant increase in VO 2 max (β = 0.78 ml/kg/min, 95% CI 0.55-1.01; P < 0.001; β = 0.51 ml/kg/min, 95% CI 0.23-0.79; P = 0.001, respectively)., Conclusions: We found an independent and robust association between serum vitamin D levels and CRF, but our results need to be validated with clinical trials examining the effect of vitamin D supplementation on CRF.

Objective: To compare clinical outcome of topical conventional with topical heparin treatment in 2nd degree or partial thickness (PTB) burn patients., Methods: Patients, between the ages of 14 and 60 years with 2nd degree burns involving <20%. Total body surface area (TBSA) on front of chest, abdomen and upper limbs excluding hands and lower limbs were enrolled from September 2015 to August 2016. Patients were randomized to conventional or heparin treatment groups. Clinical outcome measured were healed wound size, pain scores and total consumption of analgesic medication required to relieve pain. Safety of the treatment and adverse events were also measured RESULTS: Out of 66 patient included in study mean (SD) age of participants was 27 (10) years, of which 59% were males. Mean (SD) TBSA burn was 14% (3) [23 (35%) had SPTB, and 43 (65%) had DPTB]. The burn injury was caused by flames in 68% and by hot liquids in 32% patients. There was no statistically significant difference in distribution of patients according to age, gender, TBSA burn, etiology or depth of burns in the two treatment groups. As compared to conventional treatment group, heparin treatment group had significantly better outcomes. Number of days needed for wound healing was significantly lower in the heparin group than the conventional group (SPTB 14±1 vs. 20±4 days; P-value <0.000 and for DPTB, 15±3 vs. 19±2 days; P-value <0.003). Mean pain score was also lower in the heparin group (for both SPTB and DPTB 3±1 vs. 7±1; P-value <0.000). Similarly, total consumption of analgesic medication was significantly less in the heparin group (53±27 vs. 119±15mg; P-value <0.000 for SPTB and 46±6 vs. 126±12mg; P-value <0.000 for DPTB). In both groups, no patient had wound infection, skin necrosis, leucopenia, thrombocytopenia, worsening renal function, or abnormal liver enzymes CONCLUSION: Treatment of second degree or partial thickness burns (PTB) with topical heparin is superior to conventional treatment in terms of wound healing as well as for pain control. The treatment with topical heparin is well-tolerated and is without higher adverse effects., (Copyright © 2018. Published by Elsevier Ltd.)

Hepatic encephalopathy (HE) is characterized by altered sensorium and is the most common indication for hospitalization among patients with cirrhosis. Liver societal guidelines for inpatient HE revolve around identification of potential precipitants. In this retrospective study, we aimed to determine adherence to societal guidelines for evaluation of HE in 78 inpatients. The adherence rate to societal recommended guidelines for workup of HE was low, with only 17 (22%) patients having complete diagnostic workup within 24 hours of admission. Notably, 23 (30%) patients were not subjected to blood culture analysis, 16 (21%) were missing urinalysis, and 15 (20%) were missing chest radiograph. In patients with ascites (N = 34), 26 (77%) did not have a diagnostic paracentes is to exclude spontaneous bacterial peritonitis. In contrast, serum ammonia determination, a laboratory test not endorsed by societal guidelines for workup of HE, was ordered in 74 (95%) patients. These findings underscore the limited adherence to societal guidelines in hospitalized patients with HE.

Background: Geographically localized care teams may demonstrate improved communication between team members and patients, potentially enhancing coordination of care. However, the impact of geographically localized team on patient experience scores is not well understood., Objective: To compare experience scores of patients on resident teams home clinical units with patients assigned to them off of their home units over a 10-year period., Participants: Patients admitted to any of the 4 chief resident staffed internal medicine inpatient service were included. Patients admitted to the house-staff teams' home clinical unit comprised the exposure group and their patients off of their home units comprised the control patients., Measurement: Top-box experience scores calculated from the physician Hospital Consumer Assessment of Healthcare and Provider Systems (HCAHPS) and Press Ganey patient satisfaction surveys., Results: There were 3012 patients included in the study. There were no significant differences in experience scores with physician communication, nursing communication, pain, or discharge planning between the 2 groups. Patients did not report satisfaction more often with the time physicians spent with them on localized teams (48.6% vs 47.5%; P = .54) or that staff were better at working together (63.2% vs 61.3%; P = .29). This did not change during a 45-month period when the proportion of patients on home units exceeded 75% and multidisciplinary rounds were started., Conclusion: Patients cared for by geographically localized teams did not have better patient experience. Other factors such as physician communication skills or limited time spent in direct care may overshadow the impact of having localized teams. Further research is needed to better understand organizational, team, and individual factors impacting patient experience., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Current research on the relationship between phytoestrogens and mortality has been inconclusive. We explored the relationship between genistein, a phytoestrogen, and mortality in a large cohort representative of the United States population., Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999-2010. Normalized urinary genistein (nUG) was analyzed as a log-transformed continuous variable and in quartiles. Mortality data were obtained from the National Death Index and matched to the NHANES participants. Survival analyses were conducted using the Kaplan-Meier analysis. Cox proportional hazard models were constructed for all-cause and cause-specific mortality without and with adjustment for potential confounding variables., Results: Of 11,497 participants, 944 died during the 64,443 person-years follow-up. The all-cause mortality rate was significantly lower in the lowest quartile compared to the highest quartile (incidence rate ratio = 2.14, 95%CI = 1.76 to 2.60). Compared to the lowest quartile, the highest quartile had significantly higher adjusted all-cause (HR = 1.57, 95%CI = 1.23 to 2.00), cardiovascular (HR = 1.67, 95%CI = 1.04 to 2.68), and other-cause (HR = 1.85, 95%CI = 1.33 to 2.57) mortality., Conclusion: We found that high urinary genistein levels were associated with increased risk of all-cause, cardiovascular, and other-cause mortality. This is contrary to popular opinion on the health benefits of genistein and needs further research., Competing Interests: The authors have declared that no competing interests exist.

Platelet lymphocyte ratio (PLR) is a novel marker of inflammation that has gained popularity, especially in prognostication of cardiac diseases and malignant conditions. Several studies have examined the relationship between PLR and disease-specific mortality but none has examined this relationship with all-cause mortality in general population. Therefore, we examined the relationship between PLR and all-cause mortality using data from the National Health and Nutrition Examination Survey (NHANES) from the year 1999 to 2010. The role of PLR in predicting all-cause mortality was evaluated using Cox proportional hazards model adjusting for age, race, gender, smoking history, diabetes, hypertension, serum cholesterol, estimated glomerular filtration rate, serum c-reactive protein, and body mass index. Differential effect of age was examined using difference of differences analysis. Of the 27321 individuals, 2581 died during 171223 person-year follow-up. Mean PLR was significantly higher in participants who died than those who were living at the end of follow-up (145.7 vs. 133.0, respectively, p < 0.001). Individuals in the fourth quartile of PLR were at significantly higher risk of mortality than those in the first quartile (HR = 1.26, 95% CI: 1.08-1.47, p = 0.004 and adjusted HR = 1.33, HR, 95% CI: 1.15-1.54, p < 0.001, respectively). When examining the differential effect of age, association between PLR and mortality was seen in the elderly but not in the middle age or younger participants. Elevated PLR is associated with increased all-cause mortality, especially in the elderly. Further studies examining the mechanism through which PLR may increase mortality are needed.

Context: Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive., Objective: The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms., Materials and Methods: Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism., Results: In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium., Discussion and Conclusions: The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation.

Background The hormones of the hypophysis-thyroid axis (HTA), thyroid stimulating hormone (TSH), and thyroid hormones, L-thyroxine (T4) and 3, 3', 5-L-triiodothyronine (T3), modulate the metabolism, differentiation, and proliferation of almost every cell in the body. Several studies have examined the effect of HTA hormones on platelet count and mean platelet volume (MPV), but have reported inconsistent results. Our aim was to examine the association between HTA hormones and platelet count and MPV in a large cohort of the adult population of the United States. Methods  We used the continuous National Health and Nutritional Examination Survey (NHANES) which made available data on HTA hormones (1999-2000, 2001-2002, 2007-2008, 2009-2010, and 2011-2012) to examine the association between HTA hormones and platelet count and MPV. Analyses were performed with adjustments for the complex survey sampling methods of NHANES data. Unadjusted and adjusted generalized linear regressions were performed to examine the relationship between HTA hormones and platelet count and MPV. Regression models were adjusted for age, sex, race, alcohol use, smoking status, serum c-reactive protein, red blood cell folate, diabetes mellitus, glomerular filtration rate, body mass index, and hypertension. Results Of the 10,619 individuals eligible for inclusion in the analyses, 5,267 (49.6%) were females and 2,132 (20.08%) were African Americans. The mean ± standard deviation of platelet count was 256.4 ± 67.1 10 9 /L, MPV 8.04 ± 0.92 fL, serum T4 7.92 ± 1.68 mg/dL, and serum T3 114.08 ± 24.6 ng/dL. In unadjusted analyses, an increase in the serum levels of T4 or T3 was associated with a significant increase in the platelet count and MPV (all p -values < 0.05). In contrast, an increase in serum TSH level was associated with a significant decrease in the platelet count ( p -value = 0.05) but had no effect on MPV. After adjustment for potential confounders, serum T4 levels were significantly associated with platelet count but not with MPV. Individuals in the lowest quartile of T4 had 18.73 x 10 9 /L lower platelet count than individuals in the upper-most quartile ( p -value = 0.03). Serum TSH and serum T3 levels had no effect on platelet count or MPV after adjusting for potential confounding variables. Conclusions We report that only serum T4 levels, and not TSH or T3 levels, are independently associated with platelet count and there is no independent association between HTA hormones and MPV. Our findings suggest a possible role of serum T4 on thrombopoiesis or on platelet lifespan., Competing Interests: The authors have declared that no competing interests exist.

Background: Hospital-level studies have found an inverse relationship between patient experience and readmissions. However, based on typical survey response time, it is unclear if patients are able to respond to surveys before they get readmitted and whether being readmitted might be a driver of poor experience scores (reverse causation)., Objective: Using patient-level Hospital Consumer Assessment of Healthcare Providers and Systems (HCHAPS) and Press Ganey data to examine the relationship between readmissions and experience scores and to distinguish between patients who responded before or after a subsequent readmission., Design: Retrospective analysis of 10-year HCAHPS data., Setting: Single tertiary care academic hospital., Participants: Patients readmitted within 30 days of an index hospitalization who received an HCAHPS survey linked to index admission comprised the exposure group. This group was divided into those who responded prior to readmission and those who responded after readmission. Nonreadmitted patients comprised the control group., Analysis: Multivariable-logistic regression to analyze the association between HCHAPS and Press Ganey scores and 30-readmission status, adjusted for patient factors., Results: Only 15.8% of the readmitted patients responded to the survey prior to readmission, and their scores were not significantly different from the nonreadmitted patients. The patients who responded after readmission were significantly more dissatisfied with physicians (doctors listened 73.0% vs 79.2%, aOR 0.75, P < .0001), staff responsiveness, (call button 50.0% vs 59.1%, aOR 0.71, P < .0001) pain control, discharge plan, noise, and cleanliness of the hospital., Conclusions: Our findings suggest that poor patient experience may be due to being readmitted, rather than being predictive of readmission., (© 2018 Society of Hospital Medicine.)

Background: Genistein, a phytoestrogen with similarities to female sex hormones, has been shown to protect against oxidative stress and fibrosis in nonalcoholic fatty liver injury in animal studies. However, few studies have examined genistein's effects on liver function in humans., Participants and Methods: We analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2010. Individuals younger than 21 years, with viral hepatitis, or with serum alanine aminotransferase (ALT) at the extremes of distribution (5% on each extreme) were excluded. Urinary genistein was normalized by urinary creatinine levels. The relationship between normalized urinary genistein (nUG) and serum ALT was examined using linear regression models with and without adjustment for potential confounders, and the differential effect of sex was examined using an interaction term., Results: Of the 9864 participants, 52% were female, 50% were White, 24% were elderly, 36% had hypertension, 12% had diabetes, and 8.1% were heavy alcohol drinkers. Serum ALT was significantly lower in the highest quartile compared with the lowest quartile of nUG (22.3 vs. 23.5 U/l; P<0.001). In adjusted models, individuals in the highest quartile had 0.75 U/l lower ALT levels than those in the lowest quartile (P=0.02). We found a significant difference in ALT levels between the lowest and highest quartiles of nUG in males, but not in females (difference in differences=1.77 U/l, interaction P=0.04)., Conclusion: We found a statistically significant association between higher nUG and lower serum ALT in males, but not in females. The sex-specific role of genistein in mitigating liver disease merits further study.

Objective: To compare the clinical outcomes of release of flexion contractures after burn of the hand in children using tourniquet or tumescent technique in terms of operative time, postoperative pain score, and percentage of graft take., Methods: Patients aged 3 to 12 years who required release of post-burn flexion contractures involving volar aspect of palm and fingers were enrolled from outpatient clinic. Patients were randomized in 1:1 ratio to the use of either tumescent technique or tourniquet during contracture release. Duration of procedure, postoperative pain score, percentage of graft take, and any complications were assessed and analyzed in both groups by a blinded observer., Results: Of the 160 patients randomized in the study (80 in each group), 84 (52.5%) were males. The mean±SD age of participants was 7.84±3.49 years, with no statistically significant difference in gender and age distribution between the groups. Similarly, there was no statistically significant difference in duration of surgery in both groups. However, there was a statistically significant difference in percentage of graft take at the 14th postoperative day; significantly more graft take was noted in the tumescent group (8.97±3.7cm vs. 7.26±2.6cm; P=0.001). Mean analgesia consumed in the tumescent group was significantly less than that of the tourniquet group (6.26±1.9mg vs. 9.41±2.2mg; P≤0.001). Similarly, statistically significant difference in the mean FLACC pain score was noted, with remarkably low pain score in the tumescent group., Conclusion: We found that the use of the tumescent technique for the release of flexion contracture resulted in better graft take, lower pain scores, and lesser consumption of analgesic than the use of tourniquet., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.

Purpose: Poor sleep quality and duration are associated with systemic endothelial dysfunction. However, an association between poor sleep and pulmonary endothelial dysfunction has not been elucidated. We sought to determine if there is a relationship between sleep duration and fractional exhaled nitric oxide (FeNO) concentrations as a surrogate for pulmonary endothelial function., Methods: We used three National Health and Nutrition Examination Survey (NHANES) cycles (2007-2012). Linear regression models were built with and without adjustment for age, sex, race, BMI, asthma/bronchitis, CRP, smoking, folate, renal function, respiratory infections, and steroid use. To examine a non-linear relationship, we introduced a spline, with single knot at mean sleep duration (7 h)., Results: Of 13,173 participants (50.8% male, 44.2% Caucasian), 78% slept 6-8 hours (h). FeNO was significantly higher in the group sleeping 6-8 h (17.3 ± 14.9 ppb) than in the other two groups (16.0 ± 13.0 ppb, 15.9 ± 12.7 ppb for <6 and >8 h respectively; P < 0.001). In unadjusted linear regression, FeNO increased by 1.1 ppb for each hour increase in sleep up to 7 h (P < 0.001). Increased sleep duration beyond 7 h saw a 0.96 ppb decrease in FeNO (P < 0.001). After adjustment for confounders, FeNO increased by 1.09 ppb for each hour of sleep up to 7 h (P = 0.001) and decreased by 0.71 ppb for each hour after (P = 0.02)., Conclusion: Sleeping less or more than 7 h is associated with pulmonary endothelial dysfunction as measured by FeNO. Further study is needed to evaluate mechanism(s) of this association and validity of FeNO as a marker of endothelial function.

Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01); resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0) and the tissue expression of proteins these were derived from determined (GTex). MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA) with an IC50 of <500 nM, and URD, had 5,386 (p<0.01). To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.

Objectives: Early determination of hospital discharge disposition status at an acute admission is extremely important for stroke management and the eventual outcomes of patients with stroke. We investigated the hospital discharge disposition of patients with stroke residing in Tennessee and developed a predictive tool for clinical adoption. Our investigational aims were to evaluate the association of selected patient characteristics with hospital discharge disposition status and predict such status at the time of an acute stroke admission., Methods: We analyzed 127,581 records of patients with stroke hospitalized between 2010 and 2014. Logistic regression was used to generate odds ratios with 95% confidence intervals to examine the factor outcome association. An easy-to-use clinical predictive tool was built by using integer-based risk scores derived from coefficients of multivariable logistic regression., Results: Among the 127,581 records of patients with stroke, 86,114 (67.5%) indicated home discharge and 41,467 (32.5%) corresponded to facility discharge. All considered patient characteristics had significant correlations with hospital discharge disposition status. Patients were at greater odds of being discharged to another facility if they were women; older; black; patients with a subarachnoid or intracerebral hemorrhage; those with the comorbidities of diabetes mellitus, heart disease, hypertension, chronic kidney disease, arrhythmia, or depression; those transferred from another hospital; or patients with Medicare as the primary payer. A predictive tool had a discriminatory capability with area under the curve estimates of 0.737 and 0.724 for derivation and validation cohorts, respectively., Conclusions: Our investigation revealed that the hospital discharge disposition pattern of patients with stroke in Tennessee was associated with the key patient characteristics of selected demographics, clinical indicators, and insurance status. These analyses resulted in the development of an easy-to-use predictive tool for early determination of hospital discharge disposition status.

Background: Studies report high burnout prevalence among resident physicians, with little consensus on methods to effectively reduce it., Objective: This systematic literature review explores the efficacy of interventions in reducing resident burnout., Methods: PubMed, Embase, and Web of Science were searched using these key words: burnout and resident , intern , or residency . We excluded review articles, editorials, letters, and non-English-language articles. We abstracted data on study characteristics, population, interventions, and outcomes. When appropriate, data were pooled using random effects meta-analysis to account for between-study heterogeneity. Study quality was assessed using Newcastle-Ottawa Scale (cohort studies) and Jadad scale (randomized control trials [RCTs])., Results: Of 1294 retrieved articles, 19 (6 RCTs, 13 cohort studies) enrolling 2030 residents and examining 12 interventions met criteria, with 9 studying the 2003 and 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour restrictions. Work hour reductions were associated with score decrease (mean difference, -2.73; 95% confidence interval (CI) -4.12 to -1.34; P  < .001) and lower odds ratio (OR) for residents reporting emotional exhaustion (42%; OR = 0.58; 95% CI 0.43-0.77; P  < .001); a small, significant decrease in depersonalization score (-1.73; 95% CI -3.00 to -0.46; P  = .008); and no effect on mean personal accomplishment score (0.93; 95% CI -0.19-2.06; P  = .10) or for residents with high levels of personal accomplishment (OR = 1.01; 95% CI 0.67-1.54; P  = .95). Among interventions, self-care workshops showed decreases in depersonalization scores, and a meditation intervention reduced emotional exhaustion., Conclusions: The ACGME work hour limits were associated with improvement in emotional exhaustion and burnout., Competing Interests: Conflict of interest: Dr Qayyum is a consultant for Sunovion Pharmaceuticals Inc.

Background: There is a glaring lack of published evidence-based strategies to improve the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient experience scores on the physician domain. Strategies that have been used are resource intensive and difficult to sustain., Objective: We hypothesized that prompting providers to assess their own etiquette-based practices every 2 weeks over the course of 1 year would improve patient experience on the physician domain., Design: Randomized controlled trial., Setting: 4 acute care hospitals., Participants: Hospitalists., Intervention: Hospitalists were randomized to the study or the control arm. The study arm was prompted every 2 weeks for 12 months to report how frequently they engaged in 7 best-practice bedside etiquette behaviors. Control arm participants received similarly worded questions on quality improvement behaviors., Measurement: Provider experience scores were calculated from the physician HCAHPS and Press Ganey survey provider items., Results: Physicians reported high rates of etiquette-based behavior at baseline, and this changed modestly over the study period. Self-reported etiquette behaviors were not associated with experience scores. The difference in difference analysis of the baseline and postintervention physician experience scores between the intervention arm and the control arm was not statistically significant (P = 0.71)., Conclusion: In this 12-month study, biweekly reflection and reporting of best-practice bedside etiquette behaviors did not result in significant improvement on physician domain experience scores. It is likely that hospitalists' self-assessment of their bedside etiquette may not reflect patient perception of these behaviors. Furthermore, hospitalists may be resistant to improvement in this area since they rate themselves highly at baseline. Journal of Hospital Medicine 2017;12:402-406., (© 2017 Society of Hospital Medicine)

Background and Objectives: Studies have examined the relationship between serum alanine aminotransferase (ALT) and mortality with inconsistent results. Our aims were to examine the association of normal range serum ALT with mortality, to explore a nonlinear relationship between ALT and mortality, and to investigate whether age modifies this relationship., Study: We used the continuous National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Vital status of the participants was obtained by probabilistic matching between NHANES and the National Death Index. Cox proportional models were used to examine the relationship with and without adjustment for age, sex, race, BMI, hypertension, diabetes, alcohol use, serum triglycerides, prescription drug use, and glomerular filtration rate, and accounting for the sampling methodology of NHANES. Nonlinear relationship was examined using spline (single knot at 17 U/l) regression. Interaction terms were used to examine effect modification by age., Results: Higher serum ALT was associated with lower all-cause mortality [adjusted hazard ratio (HR)/ALT increment=0.98, 95% confidence interval (CI)=0.97-0.99]; however, this relationship was nonlinear and present only until 17 U/l (adjusted HR/ALT increment=0.93, 95% CI=0.91-0.95) and not thereafter. Age modified the relationship between ALT and mortality; elderly patients (>64 years) had a 6% lower adjusted mortality risk than younger (<35 years) participants (HR/ALT increment=0.94, 95% CI=0.91-0.96; interaction P<0.001)., Conclusion: Increase in serum ALT within the normal range is initially associated with lower mortality, but has no effect after 17 U/l. The elderly show a significantly larger decrease in mortality with an increase in ALT than younger individuals. The mechanisms underlying this relationship need further exploration.

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits., (Copyright © 2017 American Society of Human Genetics. All rights reserved.)

Several studies have examined an association of anti-mullerian hormone to various risk factors for mortality, however, to the best of our knowledge, no study has reported a direct relationship between anti-mullerian hormone and all-cause mortality. Therefore, we examined the relationship between baseline anti-mullerian hormone levels and subsequent all-cause mortality in men during median follow-up of 9.4 (range = 0-13) years. We used the continuous National Health and Nutrition Examination Surveys from 1999-2004 combined with National Death Index for vital status information through December 2011. Cox proportional hazard models were fit to estimate hazard ratios for all-cause mortality. Models were adjusted for age, ethnic background, body mass index, hypertension, diabetes, smoking status, c-reactive protein, total cholesterol, estimated glomerular filtration rate, serum estradiol, testosterone, sex hormone binding globulin, and androstenedione. Of the 989 men, 30 % were older than 65 years, 51 % were Caucasians, 33 % had hypertension, 27 % were active smokers, and 11 % had diabetes. Mean serum anti-mullerian hormone level of the population was 7.2 (6.3) ng/mL. During the 8943 person-years of follow-up, 164 (17 %) men died. In unadjusted analysis, each unit increase in serum anti-mullerian hormone level was associated with a 13 % lower risk of death (HR = 0.87; 95 %CI = 0.83-0.92). In multivariable models, the inverse association between serum anti-mullerian hormone levels and mortality remained significant (HR = 0.94; 95 %CI = 0.90-0.98) and was independent of confounding variables. Similarly, individuals in the highest quartile had significantly lower risk of death as compared to individuals in the lowest quartile (unadjusted HR = 0.13, 95 %CI = 0.07-0.25; adjusted HR = 0.36, 95 %CI = 0.16-0.81). We found an independent and inverse association between serum anti-mullerian hormone levels and all-cause mortality in men. The mechanism underlying this association is unknown. Further studies are needed to validate our findings in men and to examine this association in women.

Background: Several studies have examined the relationship between vitamin D (VD) and liver disease but none have explored this relationship in adults with normal liver enzymes. Our aim was to explore an independent association of VD with alanine aminotransferase (ALT) in a large sample of the US adults with liver enzymes in normal range (≤39 U/L)., Methods: We used the continuous National Health and Nutrition Examination Survey from 2001 to 2006. We excluded individuals with serum ALT>39 U/L. We built linear regression models to estimate unadjusted and adjusted (age, sex, race, diabetes, hypertension, alcohol use, smoking, and body mass index) effect sizes, taking into account the complex probability survey design., Results: Of the 12,155 participants, 6635 (54.6%) were women, mean±SD age was 49.9±19.4 years, VD was 21.9±9.2 ng/mL, and ALT was 20.9±6.9 U/L. In unadjusted analysis, VD was significantly associated with serum ALT (0.02 U/L/ng/mL of VD, P=0.007). After adjustment for confounders, VD remained statistically significantly associated with serum ALT levels (0.04 U/L, P<0.001). Similarly, individuals in the highest quartile of VD had significantly higher serum levels of ALT than those in the lowest quartile (unadjusted difference=0.98 U/L, P<0.001; adjusted difference=1.21 U/L, P<0.001)., Conclusions: We found a positive association between VD and ALT after excluding individuals with suspected active liver injury (ALT>39 U/L). The underlying mechanisms for this association are not known and needs further study.

Background: Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension., Methods: Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System., Results: Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect., Conclusions: These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

Background: Viscum album has shown inhibitory effect on different smooth muscles but underlying mechanisms in gut and vascular smooth muscles are not well defined. Additionally, the plant has also importance in managing hyperactive gut and cardiovascular disorders. The current study was aimed to probe a pharmacological base of the smooth muscle relaxant effect of V. album in gut and vascular preparations., Methods: V. album crude extract (Va. Cr) and its ethyl acetate fraction (Va. EtAc) were studied using in vitro techniques. The antispasmodic activity was performed using isolated rabbit jejunum while the vasorelaxant effects were studied in rabbit aortic rings., Results: Va. Cr and Va. EtAc inhibited spontaneous and high K(+)-induced contractions with EC50 values of 0.31 mg/mL (0.15-0.57) and 0.62 mg/mL (0.3-0.95), respectively. This advocates an antispasmodic effect probably operated through calcium channels blockade (CBB). The proposed mechanism was confirmed by a pretreatment of the tissue with Va. Cr (0.01-0.3 mg/mL), which shifted the Ca(++) concentration-response curves (CRCs) rightward, similar to verapamil. Moreover, Va. Cr showed a partial relaxation against high K(+) and PE (1 μM) induced contractions in isolated rabbit aorta rings. Va. EtAc caused complete relaxation of high K(+) precontraction and partially relaxed PE (1 μM) induced contractions, suggesting inhibitory effect on Ca(++) entry, in addition to other possible mechanisms. CRCs were shifted to the right correspondingly to verapamil when the aortic rings were pretreated with Va. Cr and Va. EtAc., Conclusions: These data indicated that Va. Cr possesses smooth muscle relaxant effect mediated through voltage-dependent Ca(++) channel blockade (CCB), which explains its spasmolytic and vasorelaxant activity. The CCB activity is concentrated more in Va. EtAc. This study provides an evidence for the medicinal importance of V. album in gut spasm and possibly hypertension.

Background: Screening adult patients for obesity and offering appropriate counseling and treatment for weight loss is recommended. However, many healthcare providers feel ill-equipped to address this topic., Objective: We examined whether didactic presentations lead to increased obesity documentation and counseling among internal medicine (IM) residents., Methods: We reviewed medical records of patients seen at the IM Resident Continuity Clinic during April 2015. Residents were provided feedback at two didactic presentations during May 2015. To examine the effect of this intervention, we repeated medical record review during June 2015. For both reviews, we abstracted patient-specific (i.e., age, body mass index [BMI], race, sex, and number of comorbid diagnoses) and resident-specific (i.e., sex and training level) data as well as evidence of obesity documentation and counseling. We used logistic regression models to examine the effect of intervention on obesity documentation and counseling, adjusting for patient- and resident-specific variables., Results: Of the 278 patients with BMI≥30 kg/m(2), 139 were seen before and 139 after the intervention. Intervention had no effect on obesity documentation or counseling with or without adjustment for confounding variables (both P>0.05). In adjusted post-hoc analyses, each additional comorbidity increased the odds of obesity documentation by 8% (OR=1.08; 95% CI=1.05-1.11; P<0.001). In addition, as compared to postgraduate year (PGY) 1 residents, PGY-3 residents were 56% (OR=0.44; 95% CI=0.21-0.95; P=0.03) less likely to counsel obese patients., Conclusions: Obesity is inadequately addressed in primary care settings, and didactic presentations were unable to increase obesity documentation or weight loss counseling. Future research to identify effective interventions is needed.

Introduction: Prior studies, using limited data from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, reported that public reporting increases satisfaction scores in all domains except physician communication. Our objective was to examine changes in patient satisfaction with physician communication using all available data., Methods: We used publicly accessible datasets: HCAHPS (2007-2013), socioeconomic datasets from the US Census Bureau, and hospital service area (HSA) dataset from the Dartmouth Atlas of Health Care. Satisfaction scores were determined by the percentage of responses to "doctors always communicated well." Hospitals were grouped into quartiles based on 2007 scores. We used multilevel models to account for correlation between within-hospital observations., Results: HCAHPS data were reported by 2273 hospitals in 2007. During the 7-year period, overall satisfaction scores with physician communication increased by 2.8% (P < 0.001). The lowest quartile hospitals had significant increase in satisfaction scores, whereas the highest quartile scores decreased (0.87% per year vs -0.23% per year; P < 0.001). These differences remained significant after adjusting for hospital and local population characteristics. Survey response rate and the number of acute-care beds and physicians in the HSA were positively associated, whereas HSA population size and being a teaching hospital were negatively associated with patient satisfaction scores (all P < 0.005)., Conclusions: Although there has been an improvement in patient satisfaction with physicians during the past 7 years, this improvement was not seen in all hospitals. The overall gap between hospitals has narrowed, which can be further improved through sharing best practices., (© 2015 Society of Hospital Medicine.)

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The study was conducted to investigate the effects of wheat based diet on the pathology of necrotic enteritis in turkeys. Turkeys were divided into four groups. Groups A and B were kept as noninoculated and fed normal commercial diet while groups C and D were challenged orally with C. perfringens and fed wheat based diet to promote the development of experimental disease. Infected turkeys showed clinical signs of depression, ruffled feathers, and dark yellowish faeces showing the most prominent disease signs in turkeys of group D with 30% mortality. Similarly, turkeys of group D showed more striking gross and histopathologic lesions as compared to turkeys of group C. The most severe gross lesions comprised intestinal distension, small necrotic spots and haemorrhages on intestine, fragile intestinal wall, and gas bubble formation in the small intestine. Histologically, inoculated turkeys showed patchy necrosis, desquamation of intestinal epithelium, and intense leukocyte infiltration in the intestine. Microscopic examination showed significant decrease in the height of intestinal villi of inoculated birds. Haematological studies showed significant influence of necrotic enteritis on the blood profile of turkeys in group D. The findings revealed that simultaneous feeding of wheat enhanced the pathology of necrotic enteritis in turkeys.

Aim: Despite several studies, the extent to which hepatitis C virus (HCV) infection is associated with chronic kidney disease (CKD) remains controversial. Thus, we examined the relationship between HCV and CKD using the continuous National Health and Nutrition Examination Survey (1999-2012)., Methods: Specimens positive for anti-HCV antibodies were retested and confirmed with recombinant immunoblot assay (RIBA). Proteinuria was defined as urine albumin creatinine ratio > 30 mg/g. CKD was defined as estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2) . We used linear and logistic regression models to examine the association between HCV and outcomes with and without adjustment for age, sex, race, hypertension, diabetes mellitus, and body mass index and accounting for the complex survey design., Results: Of the 33,729 eligible participants, HCV infection was present in 659 (1.73%). In unadjusted and adjusted analyses, HCV was associated with proteinuria (OR = 1.40, p = 0.01 and OR = 1.50, p = 0.02, respectively). In both unadjusted and adjusted analyses, individuals with HCV had significantly higher GFR than individuals without (1.4 mL/min, p = 0.04 and 2.7 mL/min, p < 0.001, respectively). We did not find an association of HCV with CKD in adjusted or unadjusted analyses., Conclusion: HCV infection is associated with proteinuria and high GFR but not with CKD. The biological mechanism of the observed association needs further study., (© 2015 Wiley Periodicals, Inc.)

Purpose: To determine the optimal time interval between tumescent local anesthesia infiltration and the start of hand surgery without a tourniquet for improved operative field visibility., Methods: Patients aged 16 to 60 years who needed contracture release and tendon repair in the hand were enrolled from the outpatient clinic. Patients were randomized to 10-, 15-, or 25-minute intervals between tumescent anesthetic solution infiltration (0.18% lidocaine and 1:221,000 epinephrine) and the start of surgery. The end point of tumescence anesthetic infiltration was pale and firm skin. The surgical team was blinded to the time of anesthetic infiltration. At the completion of the procedure, the surgeon and the first assistant rated the operative field visibility as excellent, fair, or poor. We used logistic regression models without and with adjustment for confounding variables., Results: Of the 75 patients enrolled in the study, 59 (79%) were males, 7 were randomized to 10-minute time intervals (further randomization was stopped after interim analysis found consistently poor operative field visibility), and 34 were randomized to the each of the 15- and 25-minute groups. Patients who were randomized to the 25-minute delay group had 29 times higher odds of having an excellent operative visual field than those randomized to the 15-minute delay group. After adjusting for age, sex, amount of tumescent solution infiltration, and duration of operation, the odds ratio remained highly significant., Conclusions: We found that an interval of 25 minutes provides vastly superior operative field visibility; 10-minute delay had the poorest results., Type of Study/level of Evidence: Therapeutic I., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Studies have suggested a decreased breast cancer risk in women with systemic lupus erythematosus. However, these studies enrolled younger patients identified primarily from lupus clinics. We compared the 5-year incidence of breast cancer among women with and without a diagnosis of SLE in a large population-based study of Medicare beneficiaries. We used a 20 % sample to create a cohort of 3,670,138 women from 2006 Medicare claims data with and without SLE at baseline. The study had 80 % power to detect whether the 5-year breast cancer incidence in the SLE cohort was 13 % higher or lower than the non-SLE cohort. Of the 18,423 women with SLE, 21 % were African American and 53 % were ≥65 years. The absolute age-adjusted risk for breast cancer in women with SLE was 2.23 (95 % CI 1.94-2.55) and 2.14 (95 % CI 1.96-2.34) in controls per 100 women. The overall absolute age and race adjusted incidence rate was 1.04 (95 % CI 0.90-1.21). Among women with SLE from "Others" (Hispanic, Native American, and/or Asian), the age-adjusted risk for breast cancer was 2.44 per 100 women (95 % CI 1.07-2.18), and age-adjusted incidence rate was 1.52 (95 % CI 1.07-2.18). In contrast to prior clinic-based studies, this population-based cohort study showed that the risk of breast cancer in women with SLE was not lower than in women without SLE. Women with SLE should follow routine breast cancer screening recommendations for their age group to avoid delay in diagnosis, because the presence of SLE may affect selection of early breast cancer therapies.

Background: We have previously shown that platelet aggregation has higher heritability in African Americans than European Americans. However, a genome-wide association study (GWAS) of platelet aggregation in African Americans has not been reported. We measured platelet aggregation in response to arachidonic acid, ADP, collagen, or epinephrine by optical aggregometry. The discovery cohort was 825 African Americans from the GeneSTAR study. Two replication cohorts were used: 119 African Americans from the Platelet Genes and Physiology Study and 1221 European Americans from GeneSTAR. Genotyping was conducted with Illumina 1 M arrays. For each cohort, age- and sex-adjusted linear mixed models were used to test for association between each SNP and each phenotype under an additive model., Results: Six SNPs were significantly associated with platelet aggregation (P<5×10(-8)) in the discovery sample. Of these, three SNPs in three different loci were confirmed: 1) rs12041331, in PEAR1 (platelet endothelial aggregation receptor 1), replicated in both African and European Americans for collagen- and epinephrine-induced aggregation, and in European Americans for ADP-induced aggregation; 2) rs11202221, in BMPR1A (bone morphogenetic protein receptor type1A), replicated in African Americans for ADP-induced aggregation; and 3) rs6566765 replicated in European Americans for ADP-induced aggregation. The rs11202221 and rs6566765 associations with agonist-induced platelet aggregation are novel., Conclusions: In this first GWAS of agonist-induced platelet aggregation in African Americans, we discovered and replicated, novel associations of two variants with ADP-induced aggregation, and confirmed the association of a PEAR1 variant with multi-agonist-induced aggregation. Further study of these genes may provide novel insights into platelet biology.

Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo generation of MKs from human induced pluripotent stem cells (hiPSCs) provides a renewable cell source of platelets for treating thrombocytopenic patients and allows a better understanding of MK/platelet biology. The key requirements in this approach include developing a robust and consistent method to produce functional progeny cells, such as MKs from hiPSCs, and minimizing the risk and variation from the animal-derived products in cell cultures. In this study, we developed an efficient system to generate MKs from hiPSCs under a feeder-free and xeno-free condition, in which all animal-derived products were eliminated. Several crucial reagents were evaluated and replaced with Food and Drug Administration-approved pharmacological reagents, including romiplostim (Nplate, a thrombopoietin analog), oprelvekin (recombinant interleukin-11), and Plasbumin (human albumin). We used this method to induce MK generation from hiPSCs derived from 23 individuals in two steps: generation of CD34(+)CD45(+) hematopoietic progenitor cells (HPCs) for 14 days; and generation and expansion of CD41(+)CD42a(+) MKs from HPCs for an additional 5 days. After 19 days, we observed abundant CD41(+)CD42a(+) MKs that also expressed the MK markers CD42b and CD61 and displayed polyploidy (≥16% of derived cells with DNA contents >4N). Transcriptome analysis by RNA sequencing revealed that megakaryocytic-related genes were highly expressed. Additional maturation and investigation of hiPSC-derived MKs should provide insights into MK biology and lead to the generation of large numbers of platelets ex vivo., (©AlphaMed Press.)

Greater ex vivo platelet aggregation to agonists may identify individuals at risk of acute coronary syndromes (ACS). However, increased aggregation to a specific agonist may be masked by inherent variability in other activation pathways. In this study, we inhibited the cyclooxygenase-1 (COX1) pathway with 2-week aspirin therapy and measured residual aggregation to collagen and ADP to determine whether increased aggregation in a non-COX1 pathway is associated with incident ACS. We assessed ex vivo whole blood platelet aggregation in 1,699 healthy individuals with a family history of early-onset coronary artery disease followed for 6±1.2 years. Incident ACS events were observed in 22 subjects. Baseline aggregation was not associated with ACS. After COX1 pathway inhibition, collagen-induced aggregation was significantly greater in participants with ACS compared with those without (29.0 vs. 23.6 ohms, p < 0.001). In Cox proportional hazards models, this association remained significant after adjusting for traditional cardiovascular risk factors (HR = 1.10, 95%CI = 1.06-1.15; p < 0.001). In contrast, ADP-induced aggregation after COX1 inhibition was not associated with ACS. After COX1 pathway inhibition, subjects with greater collagen-induced platelet aggregation demonstrated a significant excess risk of incident ACS. These data suggest that platelet activation related to collagen may play an important role in the risk of ACS., (© 2014 Wiley Periodicals, Inc.)

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool., (Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Inverse association between lower level of 25-hydroxyvitamin D [25(OH)D] and higher prevalence of peripheral arterial disease (PAD) among individuals with cardiovascular diseases (CVD) is known. Less is known about the relationship between 25(OH)D and ankle-brachial blood pressure index (ABPI) in asymptomatic adults. We hypothesized a nonlinear relationship between 25(OH)D and ABPI in asymptomatic adults without PAD., Methods: Data from the continuous NHANES (2001-2004) was used. Minimum of the two reported ABPI value was chosen for each individual (>18 years). Linear regression models with spline adjusted for demographic and traditional risk factors for CVD were used to examine nonlinear relationship between 25(OH)D and ABPI. Mean changes in ABPI per 10 ng/mL change in 25(OH)D were reported., Results: Mean (SD) age and 25(OH)D levels of 4979 participants (48% females) were 60.4 (13.22) years and 22.1 (8.68) ng/mL, respectively, while mean (SD) ABPI was 1.07 (0.15). We observed positive association between 25(OH)D and ABPI both in the univariable and multivariable regression models (all p < 0.05). In univariable regression with spline, a significant increase in ABPI (ß = 0.03, 95% CI: 0.02-0.04) was observed until 25(OH)D reached but not above 27 ng/mL. Similarly, in multivariable spline models, 25(OH)D was positively associated with ABPI (ß = 0.02, 95% CI: 0.01-0.03) only up to 27 ng/mL., Conclusions: In asymptomatic adults without PAD, rising serum 25(OH)D concentration but not above 27 ng/mL was associated with statistically significant increase in ABPI., (© 2014 Wiley Periodicals, Inc.)

Background: Specialty hospitals are a subset of acute-care hospitals that provide a narrower set of services than general medical hospitals (GMHs), predominantly in areas such as cardiac disease and surgery. Although specialty hospitals also advertise high patient satisfaction, this has not been examined using national data. We examined the differences in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) satisfaction scores in a national sample., Methods: HCAHPS results were obtained for July 2007 to June 2010. Specialty hospitals were identified using the American Hospital Association's Annual Survey, the Physician Hospital Association's directory, a name search of hospitals on the HCAHPS database, contact with experts, and online searches. Multiple linear regression was performed to examine the relationship between overall satisfaction and hospital specialty status, survey response rate, and subdomains of patient satisfaction., Results: We identified 188 specialty hospitals and 4368 GMHs. Specialty hospitals were disproportionately located in states that do not require Certification Of Need (47.9%), and had a higher overall patient satisfaction score (86.6 vs 67.8%, P < 0.0001) and survey response rates (49.6% vs 32.2%, P < 0.0001). After adjusting for response rate, the difference in overall patient satisfaction decreased by >50% (from 18.5 to 8.7) but remained significantly higher (P < 0.0001). Similar results were obtained for patient satisfaction subdomains., Conclusion: Specialty hospitals have a significantly higher overall HCAHPS patient satisfaction score than GMHs, although more than half of this difference disappears when adjusted for survey response rate. Comparisons among healthcare organizations should take into account survey response rates., (© 2014 Society of Hospital Medicine.)

Background: Although age and sex distributions of calcified coronary plaque have been well described in the general population, noncalcified plaque (NCP) distributions remain unknown. This is important because NCP is a putative precursor for clinical coronary artery disease and could serve as a sentinel for aggressive primary prevention, especially in high-risk populations. We examined the distributions of NCP and calcified coronary plaque in healthy 30- to 74-year-old individuals from families with early onset coronary artery disease., Methods and Results: Participants in the GeneSTAR family study (N=805), mean age 51.1±10.8 years, 56% women, were screened for coronary artery disease risk factors and coronary plaque using dual-source computed tomographic angiography. Plaque volumes (mm(3)) were quantified using a validated automated method. The prevalence of coronary plaque was 57.8% in men and 35.8% in women (P<0.0001). NCP volume increased with age (P<0.001) and was higher in men than women (P<0.001). Although NCP, as a percentage of total plaque, was inversely related to age (P<0.01), NCP accounted for most of the total plaque volume at all ages, especially in men and women <55 years (>70% and >80%, respectively). Higher Framingham risk was associated with the number of affected vessels (P<0.01), but 44% of men and 20.8% of women considered intermediate risk had left main and 3-vessel disease involvement., Conclusions: The majority of coronary plaque was noncalcified, particularly in younger individuals. These findings support the importance of assessing family history and suggest that early primary prevention interventions may be warranted at younger ages in families with early onset coronary artery disease., (© 2014 American Heart Association, Inc.)

Context: Hyperhomocysteinemia is an independent risk factor for premature atherosclerosis and thromboembolism. 25-Hydroxyvitamin D [25(OH)D] may modulate the expression of genes involved in homocysteine metabolism., Objective: Little is known about the relationship between homocysteine and 25(OH)D. We hypothesized an inverse and nonlinear association between 25(OH)D and homocysteine., Design: We analyzed data from the continuous National Health and Nutrition Examination Survey 2001-2006 for asymptomatic adults (≥18 y)., Setting: Linear regression models with spline adjusted for cardiovascular disease risk factors were used to explore nonlinearity., Main Outcomes Measure: Mean change (β-coefficients with 95% confidence intervals) in homocysteine was reported per 10 ng/mL change in 25(OH)D., Results: Mean (SD) age and homocysteine levels of 14 630 participants were 47.2 (20) years and 8.8 (4.7) μmol/L, respectively, whereas the median (interquartile range) of 25(OH)D was 21 (15-27) ng/mL. Without using spline, we observed an inverse relation between homocysteine and 25(OH)D both in simple [-0.25 (-0.34 to -0.02) μmol/L] and multivariable [-0.13 (-0.18 to -0.01) μmol/L] regression. With spline, in a univariate model, an increase in 25(OH)D was associated with a significant decrease in homocysteine [-0.56 (-0.75 to -0.37) μmol/L] until 25(OH)D reaches but not if above its median (21 ng/mL). Similarly, in multivariable spline models, the inverse relationship between homocysteine and 25(OH)D remain significant [-0.49 (-0.67 to -0.31) μmol/L] only below the population median of 25(OH)D., Conclusions: From a large community-based cohort of asymptomatic adults, we found an inverse relation between 25(OH)D and homocysteine among those with 25(OH)D concentration of 21 ng/mL or less. We did not observe any statistical decrease in homocysteine once 25(OH)D concentration rose above 21 ng/mL.