Patient care ownership in medical students: a validation study.

BACKGROUND: Psychological Ownership is the cognitive-affective state individuals experience when they come to feel they own something. The construct is context-dependent reliant on what is being owned and by whom. In medical education, this feeling translates to what has been described as "Patient Care Ownership," which includes the feelings of responsibility that physicians have for patient care. In this study, we adapted an instrument on Psychological Ownership that was originally developed for business employees for a medical student population. The aim of this study was to collect validity evidence for its fit with this population. METHODS: A revised version of the Psychological Ownership survey was created and administered to 182 medical students rotating on their clerkships in 2018-2019, along with two other measures, the Teamwork Assessment Scale (TSA) and Maslach Burnout Inventory (MBI) Survey. A confirmatory factor analysis (CFA) was conducted, which indicated a poor fit between the original and revised version. As a result, an exploratory factor analysis (EFA) was conducted and validity evidence was gathered to assess the new instruments' fit with medical students. RESULTS: The results show that the initial subscales proposed by Avey et al. (i.e. Territoriality, Accountability, Belongingness, Self-efficacy, and Self-identification) did not account for item responses in the revised instrument when administered to medical students. Instead, four subscales (Team Inclusion, Accountability, Territoriality, and Self-Confidence) better described patient care ownership for medical students, and the internal reliability of these subscales was found to be good. Using Cronbach's alpha, the internal consistency among items for each subscale, includes: Team Inclusion (0.91), Accountability (0.78), Territoriality (0.78), and Self-Confidence (0.82). The subscales of Territoriality, Team Inclusion, and Self-Confidence were negatively correlated with the 1-item Burnout measure (P = 0.01). The Team Inclusion subscale strongly correlated with the Teamwork Assessment Scale (TSA), while the subscales of Accountability correlated weakly, and Self-Confidence and Territoriality correlated moderately. CONCLUSION: Our study provides preliminary validity evidence for an adapted version of Avey et al.'s Psychological Ownership survey, specifically designed to measure patient care ownership in a medical student population. We expect this revised instrument to be a valuable tool to medical educators evaluating and monitoring students as they learn how to engage in patient care ownership.

Atopic Dermatitis and the Risk of Infection in End-Stage Renal Disease.

Background and Objectives: Atopic dermatitis (AD), also known as eczema, is a common chronic inflammatory skin condition affecting 16.5 million adults in the United States. AD is characterized by an impaired epidermal barrier that can predispose individuals to infection. End-stage renal disease (ESRD) is also commonly complicated by infections due to chronic vascular access and immune-system dysfunction, possibly related to uremia. Multiple studies have reported that renal disease is a common comorbidity in adults with atopic dermatitis. The aim of this study was to determine whether AD is a risk factor for certain infections in patients with ESRD. Materials and Methods: Using the United States Renal Data System, a retrospective cohort analysis was conducted on adult ESRD patients initiating dialysis between 2004 and 2019 to investigate associations between infections and AD in this population. Results: Of 1,526,266 patients, 2290 were identified with AD (0.2%). Infectious outcomes of interest were bacteremia, septicemia, cellulitis, herpes zoster, and conjunctivitis. In all infectious outcomes except for conjunctivitis, patients with the infectious outcomes were more likely to carry a diagnosis of AD. After controlling for demographic and clinical covariates, AD was associated with an increased risk of cellulitis (adjusted relative risk (aRR) = 1.39, 95% confidence interval (CI) = 1.31-1.47) and herpes zoster (aRR = 1.67, CI = 1.44-1.94), but not with bacteremia (aRR = 0.96, CI = 0.89-1.05), septicemia (aRR = 1.02, CI = 0.98-1.08), or conjunctivitis (aRR = 0.97, CI = 0.740-1.34). Conclusions: Overall, after controlling for demographic and clinical covariates and adjusting for person-years-at-risk, AD was associated with an increased risk for some, but not all, infections within the population of patients with ESRD.

Red blood cell volume, but not platelet or plasma volume is associated with mortality in neonatal ECMO.

BACKGROUND: Blood product transfusions are necessary for critically ill neonates on extracorporeal membrane oxygenation (ECMO). Transfusions are administered in response to unstudied arbitrary thresholds and may be associated with adverse outcomes. The objective of this study was to identify relationships between blood product components and mortality in neonates receiving ECMO support for respiratory indications. STUDY DESIGN AND METHODS: A retrospective review of neonates receiving ECMO for respiratory indications from 2002 to 2019 from a single quaternary-referral neonatal intensive care unit (NICU). Demographic and outcome data and transfusion volume (ml/kg/day) were harvested from the medical record, and baseline mortality risk was assessed using NEO-RESCUERS scores. The association between volume of red blood cells (RBC), platelet, plasma transfusion rates (ml/kg/day), and mortality on ECMO were assessed after adjustment for NEO-RESCUERS score. Cox proportional hazards (CPH) competing risk model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and mortality outcome. MEASUREMENTS AND MAIN RESULTS: Among 248 neonates undergoing ECMO for respiratory failure, overall survival was 93%. RBC, platelet, and plasma volume were highly associated with mortality during ECMO in an unadjusted model. After adjusting for NEO-RESCUERS score, RBC volume was associated with increased mortality risk (HR 1.013, 95% CI 1.004-1.022, p = .0043), but platelet and plasma volume were not associated with mortality. CONCLUSIONS: RBC, but not platelet or plasma volume, is associated with mortality in neonates on ECMO. Our findings refute previous studies demonstrating an association between platelet volume and mortality for neonates on ECMO.

A randomized, double-blind, clinical pilot trial of adjunct ketone supplement compared to placebo for treating posttraumatic stress disorder.

BACKGROUND: Despite some evidence of the helpful role of ketones in some neuropsychiatric disorders, there are no clinical trials that examine these agents for posttraumatic stress disorder (PTSD). Our aim was to investigate whether ketone salt supplementation can improve PTSD symptoms in a randomized, placebo-controlled trial. METHODS: A total of 21 participants were recruited and randomized to placebo or ketone supplement. Each dose of ketone supplement included 7 g of ketones in the form of beta-hydroxybutyrate for a total of 14 g/d. Data were collected through questionnaires to assess PTSD symptoms. We used Fisher's exact tests for categorical variables and 2-sample t tests for continuous variables to examine differences in baseline values between treatment groups. Mixed models were employed to examine changes over time between groups on the PTSD Checklist for DSM-5 (PCL-5). RESULTS: There were no statistically significant differences in PCL-5 medians between the ketone and control groups at pretest (P = 1.0000) or post-test (P = .6020). The ketone group had a statistically significant decrease in median PCL-5 scores from 58.5 (pretest) to 54.0 (posttest; P = .0003) but the control group did not change (34 at pretest and at posttest; P = .4418). CONCLUSIONS: The ketone group showed a significant decrease in PCL-5 score at posttest compared with pretest that was not seen in the control group, although these changes were not statistically significant between groups. The small sample size limited the study and likely contributed to the lack of significance. Larger trials are needed to more definitively examine these findings.

Evaluating Clostridioides difficile infection (CDI) treatment duration in hematology/oncology patients receiving concurrent non-CDI antibiotics.

PURPOSE: To determine the impact of Clostridioides difficile infection (CDI) treatment duration on CDI recurrence in hematology/oncology patients receiving concurrent non-CDI antibiotics. PATIENTS AND METHODS: This multi-site, retrospective study examined hematology/oncology patients age ≥18 years hospitalized with active CDI who received ≥1 dose of concurrent non-CDI antibiotics between September 2013 and June 2019. All patients were classified by two definitions for statistical analysis: standard (10-14 days) versus prolonged (>14 days) duration of CDI treatment and non-extended (≤24 hours after stopping non-CDI antibiotics) versus extended (>24 hours after stopping non-CDI antibiotics) CDI treatment. Primary outcome was CDI recurrence within 180 days of completing CDI treatment. Secondary outcomes included hospital length of stay (LOS) as well as mortality and incidence of vancomycin-resistant enterococcus (VRE) infections at 180 days. RESULTS: Of the 198 patients included, 112 were classified as prolonged versus 86 standard duration and 138 were classified as extended versus 60 non-extended duration. After accounting for demographic differences, no difference existed in the primary outcome of CDI recurrence in either prolonged versus standard or extended versus non-extended analysis (all p > 0.05). Patients who received prolonged versus standard CDI treatment had longer LOS (p < 0.0001) while no difference existed in extended versus non-extended (p > 0.05). No difference in mortality existed in prolonged versus standard (p > 0.05) while those who received extended versus non-extended CDI treatment had significantly lower mortality (p = 0.0008). CONCLUSIONS: Neither prolonging CDI treatment beyond standard duration nor extending duration beyond end of non-CDI antibiotics was associated with decreased CDI recurrence rate.

Assessing the impact of adding acetazolamide to oral or intravenous sodium bicarbonate as compared with intravenous bicarbonate monotherapy as urinary alkalinization in adults receiving high-dose methotrexate.

PURPOSE: High-dose methotrexate (HD-MTX) requires urine alkalinization to pH ≥ 7 for adequate excretion to prevent toxicity. Due to shortages of IV sodium bicarbonate (IV-NaHCO3), few reports have demonstrated utility of oral bicarbonate (PO-NaHCO3); however, the addition of acetazolamide (Acet) has not been well described. Our study compares outcomes between alkalinization methods of IV-NaHCO3 monotherapy versus IV-NaHCO2 + Acet and PO-NaHCO3 + Acet. METHODS: A single-center, IRB exempt, retrospective review was conducted from Jan 2016 to Sept 2019 of adults receiving HD-MTX ≥ 500 mg/m2. The primary outcome was time from start of alkalinization to pH ≥ 7. Secondary outcomes included time from start of alkalinization to initiation of HD-MTX, time to MTX clearance, length of stay (LOS), percentage of urine pH assessments < 7, and incidence of MTX toxicity. Statistical analysis was performed using SAS9.4 with alpha 0.05. RESULTS: Overall demographics (n = 196 HD-MTX cycles for 55 patients) include a mean age 55 years, HD-MTX dose ~ 5400 mg/m2, and 69% with a diagnosis of lymphoma. Adjusting for baseline demographic differences among groups, median time from first dose alkalinization to pH ≥ 7 and to start of HD-MTX was longer for those receiving IV-NaHCO3 (n = 41) vs either IV-NaHCO3 + Acet (n = 70) or PO-NaHCO3 + Acet (n = 76) (p = 0.0001). HD-MTX clearance to a level < 0.1 µmol/L was not improved with the addition of Acet. No difference existed among groups for pH results < 7, LOS, or incidence of MTX toxicity (p > 0.05). CONCLUSIONS: Addition of Acet to NaHCO3 reduces time to pH ≥ 7 and initiation of HD-MTX but does not appear to improve LOS, MTX toxicities, or time to MTX clearance.

Exercise effects on arterial stiffness and heart health in children with excess weight: The SMART RCT.

INTRODUCTION: Childhood obesity and inactivity are associated with cardiovascular risk. Evidence is limited for exercise effects on arterial health in children. METHODS: One hundred and seventy-five inactive children with overweight or obesity (8-11 years, ≥85th percentile BMI, 61% female, 87% Black, 73% with obesity) were randomized to an 8-month daily after-school aerobic exercise program (40 min/day, n = 90) or a sedentary control condition (n = 85). Carotid-femoral pulse wave velocity (PWV, primary outcome, arterial stiffness), fitness, adiposity, blood pressure (BP), glucose, insulin resistance, lipids, and C-reactive protein were measured at baseline and posttest (8 months). Adiposity, fitness, and BP were measured again at follow-up, 8-12 months later. Intent-to-treat analyses were conducted using mixed models. RESULTS: The study had 89% retention, with attendance of 59% in exercise and 64% in the control condition, and vigorous exercise participation (average heart rate 161 ± 7 beats/min). Compared with controls, the exercise group had twice the improvement in fitness (VÈ®2 peak, 2.7 (95% CI 1.8, 3.6) vs. 1.3 (0.4, 2.3) mL/kg/min) and adiposity (-1.8 (-2.4, -1.1) vs. -0.8 (-1.5, -0.1)%), each p = 0.04, and a large improvement in HDL-cholesterol (0.13 (0.075, 0.186) vs. -0.028 (-0.083, 0.023) mmol/L, p < 0.0001). There was no group × time effect on other outcomes at 8 months, or on any outcomes at follow-up. The change in PWV at 8 months correlated with changes in insulin and insulin resistance (both r = 0.32), diastolic BP (r = 0.24), BMI (r = 0.22), and adiposity (r = 0.18). CONCLUSIONS: Eight months of aerobic exercise training improved fitness, adiposity, and HDL-cholesterol levels, but did not reduce arterial stiffness in children with excess weight. PWV improved as a function of insulin resistance, BP, BMI, and adiposity. Weight loss may be required to improve arterial stiffness. Exercise benefits waned after discontinuing the program.

Examining the characteristics of patients who continue participation in vs those who drop out of a PTSD clinical trial

BACKGROUND: Patients who drop out of clinical trials examining posttraumatic stress disorder (PTSD) may have different characteristics than patients who continue. These characteristics have never been examined in prior PTSD and attrition trials. Our goal was to examine how demographic and clinical characteristics of patients with PTSD impact attrition in a randomized controlled trial. METHODS: A total of 18 participants were recruited. Data were collected through questionnaires to assess PTSD, depression, and mood disorders. Fisher's exact test was used to examine the association of various categorical demographic and clinical variables with dropout. A Wilcoxon rank sum test was used to examine differences in medians. RESULTS: The median total PTSD Checklist for DSM-5 score was 38 for patients who dropped out and 53 for those who did not. The depression scale total was also lower for the dropout group (7 vs 15). The insomnia index was lower for those who did not remain in the study (15 vs 21). CONCLUSIONS: Posttraumatic stress disorder symptoms, depression, and insomnia were less severe in patients who dropped out compared with those who did not. Larger studies are needed to further examine these findings. This study could help guide future recruitment efforts for clinical trials examining PTSD.

Useful indices of thrombogenesis in the exclusion of intra-cardiac thrombus.

BACKGROUND: Cardioversion in patients with atrial fibrillation (AF) can cause cardioembolic stroke, and effective clinical management is necessary to reduce morbidity and mortality. Currently, transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli; however, a negative TEE does not eliminate the possibility of left atrial thrombus. The objective of this study was to evaluate the diagnostic value of supplementing the TEE with additional noninvasive markers to ensure thrombus absence. METHODS: A prospective study was conducted on 59 patients who underwent TEE for suspected intra-cardiac thrombi. The TEE indications included acute ischemic stroke (45.7%) and AF or flutter (59.3%). D-dimer level and white blood cell counts were assessed. RESULTS: A negative D-dimer level (<200 ng/mL) excluded the presence of intra-cardiac thrombi. Groups with either negative (n = 14) or positive (n = 45) D-dimer levels had comparable clinical characteristics. Comparing positive D-dimer-level patients with thrombus (n = 7) and without thrombus (n = 33), patients with thrombus had reduced left atrial appendage (LAA) velocity (P = .0024), reduced left ventricular ejection fraction (LVEF) (P = .0263), increased neutrophil percent (P = .0261), decreased lymphocyte percent (P = .0216), and increased monocyte counts (P = .0220). The area under the receiver operating characteristic (ROC) curve for thrombus diagnostics was larger for combinations of clinical and biochemical data than for each parameter individually. CONCLUSIONS: Supplementing the gold standard TEE with the analysis of LAA velocity, noninvasive LVEF, D-dimer, and hemostatic markers provided additional useful diagnostic information. Larger studies are needed to further validate the efficacy of supplementing the TEE to better assess patients for intra-cardiac thrombi.

Rheumatoid Arthritis and Mortality in End Stage Renal Disease.

OBJECTIVE: To determine whether rheumatoid arthritis (RA) is a risk factor for cardiovascular disease (CVD) events, all-cause mortality and cardiovascular mortality in End Stage Renal Disease (ESRD). METHODS: Cohort study of adult patients with ESRD in the United States Renal Data System (USRDS) with RA and a 5% random sample of those without RA. CVD events, all-cause mortality and cardiovascular mortality were determined in those with RA compared to those without RA using Cox Proportional Hazards modeling. RESULTS: 2,824 subjects, 407 with RA and 2,417 without RA, were included in the analyses. The duration of the study was up to 5 years, depending on mortality and initiation of dialysis. There were no significant differences in CVD events by RA status (n = 311 [76.4% RA] vs. n = 1936 [80.1% without RA], p = 0.09). Subjects with RA had a significantly shorter mean time in months from start of dialysis to an incident CVD event (20.1 ± 12.2 vs. 21.2 ± 14.1, p < 0.01) than those without RA. In multivariable adjusted models, RA was not associated with an increased risk for all-cause mortality (aHR = 1.09, 95%CI 0.94-1.27) or cardiovascular mortality (aHR = 0.95, 95% CI 0.74-1.22) within 5 years. Risk factors for all-cause mortality and cardiovascular mortality in RA included older age and a higher Charlson comorbidity index (CCI). CONCLUSIONS: Clinicians should be aware that persons with RA who develop ESRD incur cardiac events sooner than the general population. However, RA is not an independent risk factor for all-cause or cardiovascular mortality in ESRD.

Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment.

Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.

The impact of traditional literacy and education on health literacy in adolescents with asthma.

Introduction: People with low health literacy have poorer self-management of chronic diseases like asthma. Studies of parent health literacy and education level on the management of children's chronic illnesses reveal inconclusive results. We hypothesized a correlation between parent and adolescent health literacy in teens with asthma. Methods: Sociodemographic data were obtained; health literacy was assessed on adolescents and parents with three instruments: Rapid Estimate of Adolescent/Adult Literacy in Medicine (REALM), Single Item Literacy Screener (SILS) and Newest Vital Sign (NVS). Agreement between scores was examined by calculating weighted kappa statistics and performing Bowkers test of symmetry. Results: In all, 243 adolescents and 203 parents completed health literacy assessments yielding 198 paired observations. 9th-12th graders, 60.6% female, 72.7% African-American (AA), mean age: 15.3 years (±0.9). Parent education ranged from < high school (19.1%) to college graduate (24.0%). Agreement between adolescent and parent scores was poor: REALM (κw = 0.26), SILS (κw = 0.12), and NVS (κw = 0.29) and disagreement did not significantly differ by race. Positive correlations of moderate strength (overall and between racial groups) were found between reading scores and both REALM and NVS scores, and between REALM and NVS scores. Due to the inverse relationship of SILS scores with health literacy level, SILS scores (overall and between racial groups) were weakly and negatively correlated with reading scores, REALM and NVS. Conclusion: Correlation between education level and traditional literacy suggests that these are contributing factors to the health literacy of adolescents with asthma. Correlation between adolescent and caregiver health literacy was not supported.

Improved anal Cytology Sampling: Tush Brush Compared With Dacron Swab.

OBJECTIVE: The objective of this study was to determine the performance characteristics of the Tush brush (TB) compared with a saline moistened Dacron swab (DS) as anal cytology sampling devices. MATERIALS AND METHODS: TB and DS anal cytology tests were randomly collected from 146 patients presenting for anal cytology. High-resolution anoscopy and biopsies were obtained as indicated. Sensitivity and specificity as well as rates of satisfactory specimens were determined for each method using the areas under the receiver operating characteristic curve (AUCROC) and McNemar's test, respectively. Perceived discomfort of each device was determined using a visual analog scale and compared using a paired t test. RESULTS: The adjudicated AUCROC, sensitivity, and specificity were greater, but not significantly different, for the brush (0.63, 85.5, and 40.0, respectively) compared with the swab (0.50, 79.6, and 33.3, respectively) when the anal biopsy results were considered the criterion standard. In the 1 subject diagnosed with anal cancer, the swab cytology result was normal, but the brush result was abnormal. Specimen adequacy was 95.2% for the brush and 93.2% for the swab. Mean discomfort (visual analog scale) scores were swab 28.5 mm versus brush 35.6 mm (p = .0003) with both scores within the minimal to moderate discomfort range. CONCLUSIONS: Anal cytology AUCROC, sensitivity, and specificity in detecting anal neoplasia were greater using the TB when compared with the DS. A novel anal cytology sampling device designed specifically to increase the detection of anal neoplasia would be clinically beneficial.

Reimbursement Incentives to Improve Adherence to Follow-Up of Cervical Cancer Cytology Screening Results in Peru.

OBJECTIVE: The purpose of this study was to determine Peruvian women's attitudes toward novel reimbursement incentives used to improve adherence to obtaining cervical cytology test results. MATERIALS AND METHODS: Women presenting for cervical cancer screening in Peru completed a 34-item Investigational Review Board-approved questionnaire. The questionnaire determined their attitudes toward various reimbursement incentives to improve adherence to obtaining cervical cytology results. Descriptive statistics, generalized linear models, and Kruskal-Wallis tests were used in the analyses. RESULTS: Completed questionnaires were available for 997 women. Most women (51%) would be more likely to return for their Pap result if an incentive was provided, 79% (759/956) agreed that they would pay for the Pap test, and 51% (402/859) would be willing to pay 10 Soles or less. Quechua-speaking women considered follow-up more difficult (p < .0001) but were less likely to return for their Pap results (p < .0001), pay for the Pap test (p < .0001), and afford paying more than 5 Soles (p < .0001) than women who spoke Spanish or both languages. More women who earn 1000 Soles/year or less would likely return if incentivized (p < .0001), felt the incentive would help them remember to return (p = .0047), and would be willing to pay whether there was a rebate (p = .010) as compared with women earning more money. CONCLUSIONS: A reimbursement incentive program designed to improve follow-up of cervical cytology test results was acceptable to most Peruvian women. Such a behavioral-modifying program may improve patient follow-up after cervical cytology testing. Implementation may reduce the morbidity and mortality of cervical cancer in remote regions of the country.

RAS modulation prevents progressive cognitive impairment after experimental stroke: a randomized, blinded preclinical trial.

BACKGROUND: With the aging population, the prevalence and incidence of cerebrovascular disease will continue to rise, as well as the number of individuals with vascular cognitive impairment/dementia (VCID). No specific FDA-approved treatments for VCID exist. Although clinical evidence supports that angiotensin receptor blockers (ARBs) prevent cognitive decline in older adults, whether ARBs have a similar effect on VCID after stroke is unknown. Moreover, these agents reduce BP, which is undesirable in the acute stroke period, so we believe that giving C21 in this acute phase or delaying ARB administration would enable us to achieve the neurovascular benefits without the risk of unintended and potentially dangerous, acute BP lowering. METHODS: The aim of our study was to determine the impact of candesartan (ARB) or compound-21 (an angiotensin type 2 receptor--AT2R--agonist) on long-term cognitive function post-stroke, in spontaneously hypertensive rats (SHRs). We hypothesized that AT2R stimulation, either directly with C21, or indirectly by blocking the angiotensin type 1 receptor (AT1R) with candesartan, initiated after stroke, would reduce cognitive impairment. Animals were subjected to a 60-min transient middle cerebral artery occlusion and randomly assigned to either saline/C21 monotherapy, for the full study duration (30 days), or given sequential therapy starting with saline/C21 (7 days) followed by candesartan for the remainder of the study (21 days). Outcome measures included sensorimotor/cognitive-function, amyloid-ß determination, and histopathologic analyses. RESULTS: Treatment with RAS modulators effectively preserved cognitive function, reduced cytotoxicity, and prevented chronic-reactive microgliosis in SHRs, post-stroke. These protective effects were apparent even when treatment was delayed up to 7 days post-stroke and were independent of blood pressure and ß-amyloid accumulation. CONCLUSION: Collectively, our findings demonstrate that RAS modulators effectively prevent cognitive impairment after stroke, even when treatment is delayed.

Prolonged versus short infusion rates for intravenous magnesium sulfate administration in hematopoietic cell transplant patients.

PURPOSE: Hematopoietic cell transplant (HCT) recipients often require intravenous (IV) magnesium repletion due to poor dietary intake, gastrointestinal loss, and use of concomitant magnesium wasting medications. Prolonging the IV magnesium infusion rate has been postulated to reduce renal clearance and improve retention; however, limited evidence supports this hypothesis. METHODS: We reviewed autologous and allogeneic HCT recipients (n = 82) who received IV magnesium at our institution between 2014 and 2016: 41 patients received IV magnesium at a prolonged rate of 0.5 g/h and 41 patients at > 0.5 g/h (mean 2.07 g/h). Primary outcome was percent of days in which magnesium levels were in desired therapeutic range (2-2.7 mg/dL) during hospitalization. RESULTS: Baseline characteristics were similar between cohorts: no difference existed between groups in incidence of gastrointestinal graft-versus-host disease or the percentage of patients who received magnesium replacement in maintenance fluids, received concomitant oral magnesium supplementation, or received parenteral nutrition. Percent of days in desired therapeutic range was not different between groups (p = 0.3). No difference existed between groups with respect to total amount of IV magnesium repletion (22.5 vs. 21.4 g, p = 0.81) or number of days of IV replacement (7.2 vs. 6.2 days, p = 0.41). In terms of safety, there was no difference between groups with respect to incidence of hypomagnesemia or hypermagnesemia (p = 0.43 each). CONCLUSIONS: Overall, prolonging the infusion rate did not correlate with improved magnesium retention based on amount and frequency of magnesium repletion or attainment of goal levels in HCT patients.

Assessment of melanoma follow-up trends in Medicare patients: a large scale, multi-regional analysis.

BACKGROUND: Research on patient follow-up compliance after a diagnosis of melanoma has been limited. OBJECTIVE: To assess the timelines for follow-up among patients who are diagnosed with melanoma and to assess the socioeconomic and provider factors which influence follow-up adherence. METHODS: A retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was conducted to evaluate 10,813 patients who were diagnosed with melanoma from 2005-2013. RESULTS: We found that 97% of the individuals with melanoma had at least one follow-up visit, with 80.5% having their first follow-up visit within the first 6 months and 88.6% having their first follow-up visit within 12 months. Patients who had a dermatologist as the diagnosing provider were significantly more likely to follow up. Additionally, patients who returned were more likely to live in a community with a higher socioeconomic status. LIMITATIONS: Applicability of the data to a non-Medicare population and confounding variables such as co-morbid conditions are limitations. CONCLUSIONS: The majority of patients diagnosed with melanoma follow up with a provider within one year. However, socioeconomic and provider factors play important roles in influencing patient return visits.

Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial.

BACKGROUND AND PURPOSE: Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. METHODS: This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. RESULTS: A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. CONCLUSIONS: In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895.

Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk.

Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs.