Studies on human intestinal injury induced by acute exposure to γ-radiation commonly rely on use of animal models because culture systems do not faithfully mimic human intestinal physiology. Here we ...used a human Gut-on-a-Chip (Gut Chip) microfluidic device lined by human intestinal epithelial cells and vascular endothelial cells to model radiation injury and assess the efficacy of radiation countermeasure drugs in vitro. Exposure of the Gut Chip to γ-radiation resulted in increased generation of reactive oxygen species, cytotoxicity, apoptosis, and DNA fragmentation, as well as villus blunting, disruption of tight junctions, and compromise of intestinal barrier integrity. In contrast, pre-treatment with a potential prophylactic radiation countermeasure drug, dimethyloxaloylglycine (DMOG), significantly suppressed all of these injury responses. Thus, the human Gut Chip may serve as an in vitro platform for studying radiation-induced cell death and associate gastrointestinal acute syndrome, in addition to screening of novel radio-protective medical countermeasure drugs.
The mucus layer in the human colon protects against commensal bacteria and pathogens, and defects in its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. ...However, our understanding of colon physiology is limited by the lack of in vitro models that replicate human colonic mucus layer structure and function. Here, we investigated if combining organ-on-a-chip and organoid technologies can be leveraged to develop a human-relevant in vitro model of colon mucus physiology.
A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively.
The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells. Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel–dependent increase in its hydration state, but no increase in de novo mucus secretion.
This study shows the production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real time noninvasively. The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.
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Left ventricular hypertrophy (LVH) and vitamin D deficiency have been linked to hypertension (HTN) and cardiovascular disease, particularly in African Americans (AAs). Our objective was to determine ...if the addition of vitamin D to antihypertensive therapy would lead to greater regression of LV mass index (LVMI) as determined by cardiac magnetic resonance (CMR) after 1 year in vitamin D deficient AA patients with uncontrolled HTN and LVH.
This study was a randomized, double-blind, placebo-controlled, single-center study. AA patients with HTN (systolic blood pressure BP >160 mm Hg), increased LVMI, and vitamin D deficiency (<20 ng/ml) were randomized. All patients received antihypertensive therapy combined with biweekly 50,000 IU vitamin D3 (vitamin D group, n = 55) or placebo (placebo group, n = 58).
At 1 year, there were no statistical differences between the vitamin D and placebo groups in LVMI (-14.1 ± 14.6 vs. -16.9 ± 13.1 g/m2; P = 0.34) or systolic BP (-25.6 ± 32.1 vs. -25.7 ± 25.6 mm Hg; P = 0.99) reduction, respectively. Serum vitamin D levels increased significantly in the vitamin D group compared with placebo (12.7 ± 2.0 vs. 1.8 ± 8.2 ng/ml; P < 0.001).
In this high-risk cohort of AAs we did not find an association between vitamin D supplementation and differential regression of LVMI or reduction in systolic BP. However, our study suffered from a small sample size with low statistical power precluding a definitive conclusion on the therapeutic benefit of vitamin D in such patients.
Trial Number NCT01360476. Full trial protocol is available from corresponding author.
Hypertension (HTN) is an important problem in the United States, with an estimated 78 million Americans aged 20 years and older suffering from this condition. Health disparities related to HTN are ...common in the United States, with African Americans suffering from greater prevalence of the condition than whites, as well as greater severity, earlier onset, and more complications. Medication adherence is an important component of HTN management, but adherence is often poor, and simply forgetting to take medications is often cited as a reason. Mobile health (mHealth) strategies have the potential to be a low-cost and effective method for improving medication adherence that also has broad reach.
Our goal was to determine the feasibility, acceptability, and preliminary clinical effectiveness of BPMED, an intervention designed to improve medication adherence among African Americans with uncontrolled HTN, through fully automated text messaging support.
We conducted two parallel, unblinded randomized controlled pilot trials with African-American patients who had uncontrolled HTN, recruited from primary care and emergency department (ED) settings. In each trial, participants were randomized to receive either usual care or the BPMED intervention for one month. Data were collected in-person at baseline and one-month follow-up, assessing the effect on medication adherence, systolic and diastolic blood pressure (SBP and DBP), medication adherence self-efficacy, and participant satisfaction. Data for both randomized controlled pilot trials were analyzed separately and combined.
A total of 58 primary care and 65 ED participants were recruited with retention rates of 91% (53/58) and 88% (57/65), respectively. BPMED participants consistently showed numerically greater, yet nonsignificant, improvements in measures of medication adherence (mean change 0.9, SD 2.0 vs mean change 0.5, SD 1.5, P=.26), SBP (mean change -12.6, SD 24.0 vs mean change -11.3, SD 25.5 mm Hg, P=.78), and DBP (mean change -4.9, SD 13.1 mm Hg vs mean change -3.3, SD 14.3 mm Hg, P=.54). Control and BPMED participants had slight improvements to medication adherence self-efficacy (mean change 0.8, SD 9.8 vs mean change 0.7, SD 7.0) with no significant differences found between groups (P=.92). On linear regression analysis, baseline SBP was the only predictor of SBP change; participants with higher SBP at enrollment exhibited significantly greater improvements at one-month follow-up (β=-0.63, P<.001). In total, 94% (51/54) of BPMED participants agreed/strongly agreed that they were satisfied with the program, regardless of pilot setting.
Use of text message reminders to improve medication adherence is a feasible and acceptable approach among African Americans with uncontrolled HTN. Although differences in actual medication adherence and blood pressure between BPMED and usual care controls were not significant, patterns of improvement in the BPMED condition suggest that text message medication reminders may have an effect and fully powered investigations with longer-term follow-up are warranted.
Clinicaltrials.gov NCT01465217; https://clinicaltrials.gov/ct2/show/NCT01465217 (Archived by WebCite at http://www.webcitation.org/6V0tto0lZ).
The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction ...(matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.
Elevated blood pressure is a major risk factor for cardiovascular disease and stroke but patients often discount recommended behavioral changes and prescribed medications. While effective ...interventions to promote adherence have been developed, cost-effectiveness from the patient's perspective, has not been well studied. The valuation of patient time and out of pocket expenses should be included while performing cost effectiveness evaluation. The Achieve BP study uses the contingent valuation method to assess willingness to accept (WTA) and willingness to pay (WTP) among patients with a history of uncontrolled blood pressure discharged from an urban emergency department and enrolled in a larger randomized controlled trial.
WTA and WTP were assessed by asking patients a series of questions about time and travel costs and time value related to their study participation. A survey was conducted during the final study visit with patients to investigate the effectiveness of a kiosk-based educational intervention on blood pressure control. All study patients, regardless of study arm, received the same clinical protocol of commonly prescribed antihypertensive medication and met with research clinicians four times as part of the study procedures.
Thirty-eight patients were offered the opportunity to participate in the cost-effectiveness study and all completed the survey. Statistical comparisons revealed these 38 patients were similar in representation to the entire RCT study population. All 38 (100.0%) were African-American, with an average age of 49.1 years; 55.3% were male, 21.1% were married, 78.9% had a high school or higher education, and 44.7% were working. 55.9% did not have a primary care provider and 50.0% did not have health insurance. Time price linear regression analysis was performed to estimate predictors of WTA and WTP.
WTP and WTA may generate different results, and the elasticities were proportional to the estimated coefficients, with WTP about twice as responsive as WTA. An additional feature for health services research was successful piloting in a clinical setting of a brief patient-centered cost effectiveness survey.
https://clinicaltrials.gov . Registration Number NCT02069015 . Registered February 19, 2014 (Retrospectively registered).
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Hypertension is one of the most important cardiovascular disease risk factors and affects >100 million American adults. Hypertension-related health inequities are abundant in Black ...communities as Black individuals are more likely to use the emergency department (ED) for chronic disease–related ambulatory care, which is strongly linked to lower blood pressure (BP) control, diminished awareness of hypertension, and adverse cardiovascular events. To reduce hypertension-related health disparities, we developed MI-BP, a culturally tailored multibehavior mobile health intervention that targeted behaviors of BP self-monitoring, physical activity, sodium intake, and medication adherence in Black individuals with uncontrolled hypertension recruited from ED and community-based settings. Objective We sought to determine the effect of MI-BP on BP as well as secondary outcomes of physical activity, sodium intake, medication adherence, and BP control compared to enhanced usual care control at 1-year follow-up. Methods We conducted a 1-year, 2-group randomized controlled trial of the MI-BP intervention compared to an enhanced usual care control group where participants aged 25 to 70 years received a BP cuff and hypertension-related educational materials. Participants were recruited from EDs and other community-based settings in Detroit, Michigan, where they were screened for initial eligibility and enrolled. Baseline data collection and randomization occurred approximately 2 and 4 weeks after enrollment to ensure that participants had uncontrolled hypertension and were willing to take part. Data collection visits occurred at 13, 26, 39, and 52 weeks. Outcomes of interest included BP (primary outcome) and physical activity, sodium intake, medication adherence, and BP control (secondary outcomes). Results We obtained consent from and enrolled 869 participants in this study yet ultimately randomized 162 (18.6%) participants. At 1 year, compared to the baseline, both groups showed significant decreases in systolic BP (MI-BP group: 22.5 mm Hg decrease in average systolic BP and P<.001; control group: 24.1 mm Hg decrease and P<.001) adjusted for age and sex, with no significant differences between the groups (time-by-arm interaction: P=.99). Similar patterns where improvements were noted in both groups yet no differences were found between the groups were observed for diastolic BP, physical activity, sodium intake, medication adherence, and BP control. Large dropout rates were observed in both groups (approximately 60%). Conclusions Overall, participants randomized to both the enhanced usual care control and MI-BP conditions experienced significant improvements in BP and other outcomes; however, differences between groups were not detected, speaking to the general benefit of proactive outreach and engagement focused on cardiometabolic risk reduction in urban-dwelling, low-socioeconomic-status Black populations. High dropout rates were found and are likely to be expected when working with similar populations. Future work is needed to better understand engagement with mobile health interventions, particularly in this population. Trial Registration ClinicalTrials.gov NCT02955537; https://clinicaltrials.gov/study/NCT02955537 International Registered Report Identifier (IRRID) RR2-10.2196/12601
Background
Health measurement guides policies and health care decisions are necessary to describe and attain the quintuple aim of improving patient experience, population health, care team ...well-being, health care costs, and equity. In the primary care setting, patient-reported outcome measurement allows outcome comparisons within and across settings and helps improve the clinical management of patients. However, these digital patient-reported outcome measures (PROMs) are still not adapted to the clinical context of primary health care, which is an indication of the complexity of integrating these tools in this context. We must then gather evidence of their impact on chronic disease management in primary health care and understand the characteristics of effective implementation.
Objective
We will conduct a systematic review to identify and assess the impact of electronic PROMs (ePROMs) implementation in primary health care for chronic disease management. Our specific objectives are to (1) determine the impact of ePROMs in primary health care for chronic disease management and (2) compare and contrast characteristics of effective ePROMs’ implementation strategies.
Methods
We will conduct a systematic review of the literature in accordance with the guidelines of the Cochrane Methods Group and in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for its reporting. A specific search strategy was developed for relevant databases to identify studies. Two reviewers will independently apply the inclusion criteria using full texts and will extract the data. We will use a 2-phase sequential mixed methods synthesis design by conducting a qualitative synthesis first, and use its results to perform a quantitative synthesis.
Results
This study was initiated in June 2022 by assembling the research team and the knowledge transfer committee. The preliminary search strategy will be developed and completed in September 2022. The main search strategy, data collection, study selection, and application of inclusion criteria were completed between October and December 2022.
Conclusions
Results from this review will help support implementation efforts to accelerate innovations and digital adoption for primary health care and will be relevant for improving clinical management of chronic diseases and health care services and policies.
Trial Registration
PROSPERO International Prospective Register of Systematic Reviews CRD42022333513; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=333513
International Registered Report Identifier (IRRID)
DERR1-10.2196/48155
We present a 14-year-old boy with peritoneal epithelial malignant mesothelioma (PEMM). While pathology is required to make this diagnosis, radiology plays a crucial role throughout the clinical ...course of this disease. The key imaging characteristics of peritoneal mesothelioma have been previously well-described in the adult population, but there are rare reports in the pediatric population. This pediatric report highlights the multidimensional use of imaging in this disease, from the initial evaluation to therapeutic supplementation and subsequent follow-up.
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