Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.
The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age.
BackgroundDigital mental health tools have tended to use psychoeducational strategies based on treatment orientations developed and validated outside of digital health. These features do not map well to the brief but frequent ways that people use mobile phones and mobile phone apps today. To address these challenges, we developed a suite of apps for depression and anxiety called IntelliCare, each developed with a focused goal and interactional style. IntelliCare apps prioritize interactive skills training over education and are designed for frequent but short interactions.ObjectiveThe overall objective of this study was to pilot a coach-assisted version of IntelliCare and evaluate its use and efficacy at reducing symptoms of depression and anxiety.MethodsParticipants, recruited through a health care system, Web-based and community advertising, and clinical research registries, were included in this single-arm trial if they had elevated symptoms of depression or anxiety. Participants had access to the 14 IntelliCare apps from Google Play and received 8 weeks of coaching on the use of IntelliCare. Coaching included an initial phone call plus 2 or more texts per week over the 8 weeks, with some participants receiving an additional brief phone call. Primary outcomes included the Patient Health Questionnaire-9 (PHQ-9) for depression and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety. Participants were compensated up to US $90 for completing all assessments; compensation was not for app use or treatment engagement.ResultsOf the 99 participants who initiated treatment, 90.1% (90/99) completed 8 weeks. Participants showed substantial reductions in the PHQ-9 and GAD-7 (P<.001). Participants used the apps an average of 195.4 (SD 141) times over the 8 weeks. The average length of use was 1.1 (SD 2.1) minutes, and 95% of participants downloaded 5 or more of the IntelliCare apps.ConclusionsThis study supports the IntelliCare framework of providing a suite of skills-focused apps that can be used frequently and briefly to reduce symptoms of depression and anxiety. The IntelliCare system is elemental, allowing individual apps to be used or not used based on their effectiveness and utility, and it is eclectic, viewing treatment strategies as elements that can be applied as needed rather than adhering to a singular, overarching, theoretical model.Trial RegistrationClinicaltrials.gov NCT02176226; http://clinicaltrials.gov/ct2/show/NCT02176226 (Archived by WebCite at http://www.webcitation/6mQZuBGk1)
Background & Aims The aim of this study was to assess whether measurements of esophageal distensibility, made by high-resolution impedance planimetry, correlated with important clinical outcomes in patients with eosinophilic esophagitis. Methods Seventy patients with eosinophilic esophagitis (50 male, ages 18–68) underwent endoscopy with esophageal biopsy collection and high-resolution impedance planimetry using the functional lumen-imaging probe. The patients were followed prospectively for an average of 9.2 months (range 3–14 months), and the risk of food impaction, requirement for dilation; symptom severity during the follow-up period was determined from medical records. Esophageal distensibility metrics and the severity of mucosal eosinophilia at baseline were compared between patients presenting with and without food impaction and those requiring or not requiring esophageal dilation. Logistic regression and stratification assessments were used to assess the predictive value of esophageal distensibility metrics in assessing risk of food impaction, the need for dilation, and continued symptoms. Results Patients with prior food impactions had significantly lower distensibility plateau (DP) values than those with solid food dysphagia alone. Additionally, patients sustaining food impaction and requiring esophageal dilation during the follow-up period had significantly lower DP values than those who did not. The severity of mucosal eosinophilia did not correlate with risk for food impaction, the requirement for dilation during follow up, or DP values. Conclusions Reduced esophageal distensibility predicts risk for food impaction and the requirement for esophageal dilation in patients with eosinophilic esophagitis. The severity of mucosal eosinophilia was not predictive of these outcomes and had a poor correlation with esophageal distensibility.
Our findings suggest that aspirin acts on the colon to unmask a susceptibility to gut leakiness in patients with NASH. This effect may be the underlying mechanism for increased serum endotoxin, which is the second hit (after altered lipid metabolism) that is required to initiate a necroinflammatory cascade in hepatocytes which are already primed with obesity-induced abnormal lipid homoeostasis.
Objective Investigate the relationship of excess and central adiposity with pediatric psoriasis severity. Design, Setting and Participants Multi-center, cross-sectional study of 409 psoriatic children. Psoriasis was classified as mild (worst Physician’s Global Assessment (PGA) <3 with body surface area (BSA) <10%) or severe (worst PGA >3 with BSA >10%). Children were enrolled from 9 countries July 2009-December 2011. Main Outcome Measures Excess adiposity (body mass index (BMI) percentile) and central adiposity (waist circumference (WC) percentile and waist-to-height ratio). Results Excess adiposity (BMI >85th percentile) occurred in 37.8% (n=155) of psoriatics vs. 20.5% (n=42) of controls, but did not differ by severity. The odds of obesity (BMI >95th percentile) overall in psoriatics vs. controls were OR=4.29, 95% CI=1.96-9.39, but were higher with severe (OR=4.92, CI=2.20-10.99) than mild (OR=3.60, CI=1.56-8.30) psoriasis, particularly in the U.S. (OR=7.60, CI=2.47-23.34, and OR=4.72, CI=1.43-15.56, respectively). WC >90th percentile occurred in 9.3% (n=19) of controls, 14.0% (n=27) of mild, and 21.2% (n=43) of severe psoriatics internationally, and especially in the U.S. (12.0% of controls, 20.8% of mild, and 31.1% of severe psoriatics). Waist-to-height ratio was significantly higher in psoriatic (0.48) vs. control (0.46) children, but unaffected by psoriasis severity. Children with severe psoriasis at their worst, but mild at enrollment, showed no difference in excess or central adiposity from children who remained severe at enrollment. Conclusion Globally, children with psoriasis have both excess adiposity and increased central adiposity, regardless of severity. The increased metabolic risks associated with excess and central adiposity warrant early monitoring and lifestyle modification.
In recent years, there has been increasing discussion of the limitations of traditional randomized controlled trial (RCT) methodologies for the evaluation of eHealth and mHealth interventions, and in particular, the requirement that these interventions be locked down during evaluation. Locking down these interventions locks in defects and eliminates the opportunities for quality improvement and adaptation to the changing technological environment, often leading to validation of tools that are outdated by the time that trial results are published. Furthermore, because behavioral intervention technologies change frequently during real-world deployment, even if a tested intervention were deployed in the real world, its shelf life would be limited. We argue that RCTs will have greater scientific and public health value if they focus on the evaluation of intervention principles (rather than a specific locked-down version of the intervention), allowing for ongoing quality improvement modifications to the behavioral intervention technology based on the core intervention principles, while continuously improving the functionality and maintaining technological currency. This paper is an initial proposal of a framework and methodology for the conduct of trials of intervention principles (TIPs) aimed at minimizing the risks of in-trial changes to intervention technologies and maximizing the potential for knowledge acquisition. The focus on evaluation of intervention principles using clinical and usage outcomes has the potential to provide more generalizable and durable information than trials focused on a single intervention technology.
Rationale: Checklists may reduce errors of omission for critically ill patients. Objectives: To determine whether prompting to use a checklist improves process of care and clinical outcomes. Methods: We conducted a cohort study in the medical intensive care unit (MICU) of a tertiary care university hospital. Patients admitted to either of two independent MICU teams were included. Intervention team physicians were prompted to address six parameters from a daily rounding checklist if overlooked during morning work rounds. The second team (control) used the identical checklist without prompting. Measurements and Main Results: One hundred and forty prompted group patients were compared with 125 control and 1,283 preintervention patients. Compared with control, prompting increased median ventilator-free duration, decreased empirical antibiotic and central venous catheter duration, and increased rates of deep vein thrombosis and stress ulcer prophylaxis. Prompted group patients had lower risk-adjusted ICU mortality compared with the control group (odds ratio, 0.36; 95% confidence interval, 0.13-0.96; P ¼ 0.041) and lower hospital mortality compared with the control group (10.0 vs. 20.8%; P ¼ 0.014), which remained significant after risk adjustment (odds ratio, 0.34; 95% confidence interval, 0.15-0.76; P ¼ 0.008). Observed-to-predicted ICU length of stay was lower in the prompted group compared with control (0.59 vs. 0.87; P ¼ 0.02). Checklist availability alone did not improve mortality or length of stay compared with preintervention patients. Conclusions: In this single-site, preliminary study, checklist-based prompting improved multiple processes of care, and may have improved mortality and length of stay, compared with a stand-alone checklist. The manner in which checklists are implemented is of great consequence in the care of critically ill patients.
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