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OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS:A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (β coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (β coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (β coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (β coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (β coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (β coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS:Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

Background: Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms, but how it improves pain in humans is unknown. Aims:To investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signalling in IBS-C patients, in a randomised clinical trial. Methods:Patients with IBS-C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi-directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal-anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto-cortical and cortico-rectal evoked potentials.Results: Thirty-nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups.The efferent cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS-QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13). Conclusions:Linaclotide prolongs afferent gut-brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms and QOL compared to placebo.These mechanisms may explain the effects of linaclotide on pain relief in IBS-C patients. ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations.

When testing for the mean vector in a high dimensional setting, it is generally assumed that the observations are independently and identically distributed. However if the data are dependent, the existing test procedures fail to preserve type I error at a given nominal significance level. We propose a new test for the mean vector when the dimension increases linearly with sample size and the data is a realization of an M -dependent stationary process. The order M is also allowed to increase with the sample size. Asymptotic normality of the test statistic is derived by extending the central limit theorem result for M -dependent processes using two dimensional triangular arrays. Finite sample simulation results indicate the cost of ignoring dependence amongst observations.

INTRODUCTION: Treatments for fecal incontinence (FI) remain unsatisfactory because they do not remedy the underlying multifactorial dysfunction(s) including anorectal neuropathy. The aim of this study was to investigate the optimal dose frequency, clinical effects, and safety of a novel treatment, translumbosacral neuromodulation therapy (TNT), aimed at improving neuropathy. METHODS: Patients with FI were randomized to receive 6 sessions of weekly TNT treatments consisting of 600 repetitive magnetic stimulations over each of 2 lumbar and 2 sacral sites with either 1, 5, or 15 Hz frequency. Stool diaries, FI severity indices, anorectal neurophysiology and sensorimotor function, and quality of life were compared. Primary outcome measure was the change in FI episodes/week. Responders were patients with ≥50% decrease in weekly FI episodes. RESULTS: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 (5 Hz); 3.4 ± 2.5 (15 Hz); P < 0.02) in all 3 groups when compared with baseline. The 1 Hz group showed a significantly higher (P = 0.04) responder rate (91 ± 9.1%) when compared with the 5 Hz group (36 ± 18.2%) or 15 Hz (55 ± 18.2%); no difference was found between the 5 and 15 Hz groups (P = 0.667). Anal neuropathy, squeeze pressure, and rectal capacity improved significantly only in the 1 Hz (P < 0.05) group compared with baseline, but not in other groups. Quality of life domains improved significantly (P < 0.05) with 1 and 5 Hz groups. No device-related serious adverse events were noted. DISCUSSION: TNT significantly improves FI symptoms in the short term, and the 1 Hz frequency was overall better than 5 and 15 Hz. Both anorectal neuropathy and physiology significantly improved, demonstrating mechanistic improvement. TNT is a promising, novel, safe, efficacious, and noninvasive treatment for FI (see Visual Abstract, Supplementary Digital Content 3, http://links.lww.com/AJG/B598).

Background: Increasing efforts have been made in primary care settings to screen for a broad array of social determinants of health including inadequate food and nutrition, lack of education, unemployment, and inadequate housing, and to refer patients to community resources. Core tenets of primary care include integration with community resources. Methods: In the course of designing a randomized controlled trial of the effectiveness of a social determinants of health intervention aimed at adult, at-risk, African American primary care clinic patients, our research team developed a logic model to assist with the evaluation of the intervention. Results: In this article, we describe the logic model including elements of the intervention, mediator variables, and outcome variables. Conclusions: The proposed logic framework is likely to be helpful for planning, conducting, and evaluating social determinants of health interventions in primary care settings.

Background: Among breast cancer survivors age > 50 years, deaths due to cardiovascular disease account for 35% of non-cancer related deaths. The increases in cardiovascular disease among breast cancer survivors is due to the cardiotoxic effects of breast cancer treatment and to overlapping risk factors for breast cancer and cardiovascular disease. Methods: We conducted a study of a sample of 164 breast cancer patients in order to examine the frequency of cardiovascular disease. The overall objective was to examine the frequency of high blood pressure, myocardial infarction, cardiomyopathy, congestive heart failure, stroke, and venous thrombosis/thromboembolism among women who have been diagnosed with stage I-IV breast cancer and who had completed primary therapy for the disease. Data were collected by postal survey and abstraction of electronic medical records. Results: A high percentage of the women (62.8%) had a reported history of high blood pressure. Fifty percent of the women had a reported history of high cholesterol. About 8.3% of the women were current smokers and 36.0% were former smokers. About 23.8% of the women had a reported history of diabetes. About 4.9% of the women had a reported history of congestive heart failure and 6.1% had a history of stroke. Discussion: Additional studies are needed of cardiovascular risk factors and adverse cardiovascular events among breast cancer survivors. Of particular concern is whether patients with hypertension, hypercholesterolemia, and diabetes are receiving appropriate therapy to reduce their cardiovascular risk and prevent morbidity and mortality from adverse cardiovascular events.

BACKGROUND The prevalence of left atrial appendage (LAA) thrombus detection by transesophageal echocardiogram (TEE) in patients with non-valvular atrial fibrillation (AF) anticoagulated with apixaban is not well defined and identification of additional risk factors may help guide the selection process for pre-procedural TEE. The purpose of our study was to retrospectively analyze the prevalence of LAA thrombus detection by TEE in patients continuously anticoagulated with apixaban for ≥ 4 wk and evaluate for any cardiac risk factors or echocardiographic characteristics which may serve as predictors of thrombus formation. AIM To retrospectively analyze the prevalence of LAA thrombus detection by TEE in patients continuously anticoagulated with apixaban. METHODS Clinical and echocardiographic data for 820 consecutive patients with AF undergoing TEE at Augusta University Medical Center over a four-year period were retrospectively analyzed. All patients (apixaban: 226) with non-valvular AF and documented compliance with apixaban for ≥ 4 wk prior to index TEE were included. RESULTS Following ≥ 4 wk of continuous anticoagulation with apixaban, the prevalence of LAA thrombus and LAA thrombus/dense spontaneous echocardiographic contrast was 3.1% and 6.6%, respectively. Persistent AF, left ventricular ejection fraction < 30%, severe LA dilation, and reduced LAA velocity were associated with thrombus formation. Following multivariate logistic regression, persistent AF (OR: 7.427; 95%CI: 1.02 to 53.92; P = 0.0474), and reduced LAA velocity (OR: 1.086; 95%CI: 1.010 to 1.187; P = 0.0489) were identified as independent predictors of LAA thrombus. No Thrombi were detected in patients with a CHA 2 DS 2 -VASc score ≤ 1. CONCLUSION Among patients with non-valvular AF and ≥ 4 wk of anticoagulation with apixaban, the prevalence of LAA thrombus detected by TEE was 3.1%. This suggests that continuous therapy with apixaban does not completely eliminate the risk of LAA thrombus and that TEE prior to cardioversion or catheter ablation may be of benefit in patients with multiple risk factors.