Uninterrupted prolonged sitting and arterial stiffness: moderating effect of prior aerobic exercise in physically active adults.

PURPOSE: Prolonged sitting acutely increases arterial stiffness, with interruption strategies only providing limited success in offsetting these rises. Acute aerobic exercise is a potent stimulus to decrease arterial stiffness. However, limited information exists on the effectiveness of acute exercise to maintain arterial stiffness when performed prior to prolonged sitting, particularly within physically active individuals. METHODS: Using a randomized crossover design, 22 young, active individuals (50% female) performed two conditions 30 min of walking at 55-65% of heart rate reserve (EX) and 30 min of standing (STAND) followed by 2.5-h of sitting. Brachial-femoral (bfPWV) and femoral-ankle pulse wave velocity (faPWV) were assessed at Baseline, post-exercise and pre-sitting (Pre), and post-sitting (Post) as estimates of central and peripheral arterial stiffness, respectively. RESULTS: For bfPWV, no interaction, condition, or time effects were observed. For faPWV, an interaction was present (p < 0.001); compared to Baseline, there was a 6.1% decrease for EX (- 0.4 m/s, p < 0.001) and a 4.6% increase for STAND (0.3 m/s, p = 0.016) for STAND such that there was an 11.3% difference between conditions at Pre (0.7 m/s, p < 0.001). From Pre to Post, EX then increased by 11.7% (0.9 m/s p < 0.001) while STAND remained unchanged, resulting in no difference between conditions (0.1 m/s, p = 0.569). CONCLUSIONS: While aerobic exercise resulted in a significant decrease in faPWV prior to sitting, the prior exercise bout did not confer a protective effect against the deleterious effects of uninterrupted sitting. Future work should investigate the combined effect of prior exercise and sitting interruption strategies on markers of arterial stiffness.

The impact of uninterrupted sitting on central and peripheral cardiovascular function in pre-menopausal and post-menopausal women.

Independently, both prolonged uninterrupted sitting and the onset of menopause negatively impact markers of cardiovascular risk. Whether their combination augment these responses additively remains unknown. This study assessed whether prolonged uninterrupted sitting causes greater central and peripheral cardiovascular dysfunction in post-menopausal women compared to pre-menopausal women. To address this, 23 healthy women (13 pre-menopausal [43.77 ± 4.30 years] and 10 post-menopausal [57.20 ± 8.55 years]) sat uninterrupted for 2-h. Carotid-femoral pulse wave velocity (cf-PWV), pulse wave analysis (PWA), lower limb venous pooling (HHb), and calf circumference were assessed pre-and post-sitting using general linear mixed models, with age as a covariate. Changes in MAP over time (both between and within groups) was assessed using a two-way repeated-measures-ANOVA. There were no significant interactions for any outcome measures. However, for cf-PWV, there was a significant main effect of group (Δ = 0.854 ± 0.354 m s-1; p = 0.026, ηp2 = 0.707). For PWA, only heart rate (HR) and pressure forwards (Pf) showed significant main effects 13 of time [Δ = 6 ± 1 bts-min-1, p < 0.001, ηp2 = 0.861] and group [Δ = 3.893 ± 1.450 mmHg, p = 0.016, ηp2 = 0.271], respectively. Both HHb (Δ = 2.737 ± 0.952, p = 0.009, ηp2 = 0.742) and calf circumference (Δ = 0.812 ± 0.128 cm, p < 0.001, ηp2 = 0.863) significantly increased over time. Whilst post-menopausal women demonstrated greater overall arterial stiffness (increased cf-PWV at baseline), there was no difference in cardiovascular response (central or peripheral) to 2-h of prolonged sitting between the pre- and post-menopausal women.

The 24-h activity cycle and cardiovascular outcomes: establishing biological plausibility using arterial stiffness as an intermediate outcome.

This review proposes a biologically plausible working model for the relationship between the 24-h activity cycle (24-HAC) and cardiovascular disease. The 24-HAC encompasses moderate-to-vigorous physical activity (MVPA), light physical activity, sedentary behavior (SB), and sleep. MVPA confers the greatest relative cardioprotective effect, when considering MVPA represents just 2% of the day if physical activity guidelines (30 min/day) are met. While we have well-established guidelines for MVPA, those for the remaining activity behaviors are vague. The vague guidelines are attributable to our limited mechanistic understanding of the independent and additive effects of these behaviors on the cardiovascular system. Our proposed biological model places arterial stiffness, a measure of vascular aging, as the key intermediate outcome. Starting with prolonged exposure to SB or static standing, we propose that the reported transient increases in arterial stiffness are driven by a cascade of negative hemodynamic effects following venous pooling. The subsequent autonomic, metabolic, and hormonal changes further impair vascular function. Vascular dysfunction can be offset by using mechanistic-informed interruption strategies and by engaging in protective behaviors throughout the day. Physical activity, especially MVPA, can confer protection by chronically improving endothelial function and associated protective mechanisms. Conversely, poor sleep, especially in duration and quality, negatively affects hormonal, metabolic, autonomic, and hemodynamic variables that can confound the physiological responses to next-day activity behaviors. Our hope is that the proposed biologically plausible working model will assist in furthering our understanding of the effects of these complex, interrelated activity behaviors on the cardiovascular system.

Acute sedentary behavior and cardiovascular disease research: standardizing the methodological posture.

Sedentary behavior has been identified as an independent predictor of future cardiovascular disease risk and all-cause mortality. To explain this association, a growing body of literature has sought to investigate the physiological underpinnings of this association with the goal of developing a biologically plausible model. In time, this biologically plausible model can be tested, and effective, translatable public health guidelines can be developed. However, to ensure that evidence across studies can be effectively synthesized, it is necessary to ensure their congruency and comparability. Although there are several key factors that should be considered and controlled across prolonged sitting studies, one pertinent issue is that of participant posture. There is currently a discourse within the literature regarding the posture that cardiovascular assessments are performed in and rest periods between posture transitions and subsequent measures. This perspectives piece makes the case for standardizing approaches across the research area and offers practical recommendations for future work.

Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis.

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).

Endothelium function dependence of acute changes in pulse wave velocity and flow-mediated slowing.

Flow-mediated slowing (FMS), defined as the minimum pulse wave velocity (PWVmin) during reactive hyperemia, is potentially a simple, user-objective test for examining endothelial function. The purpose of the current study was to determine the effects of a known endothelial dysfunction protocol on arm PWV and PWVmin. Complete data were successfully collected in 22 out of 23 healthy adults (23.8 years [SD 4.1], 16 F, 22.8 kg/m2 [SD 2.8]). Local endothelial dysfunction was induced by increasing retrograde shear stress in the upper arm, through inflation of a distal (forearm) tourniquet to 75 mmHg, for 30 min. Pre- and post-endothelial dysfunction, PWV was measured followed by simultaneous assessment of PWVmin and flow-mediated dilation (FMD). PWV was measured between the upper arm and wrist using an oscillometric device, and brachial FMD using ultrasound. FMD (%) and PWVmin (m/s) were calculated as the maximum increase in diameter and minimum PWV during reactive hyperemia, respectively. Endothelial dysfunction resulted in a large effect size (ES) decrease in FMD (∆ = -3.10%; 95% CI: -4.15, -2.05; ES = -1.3), and a moderate increase in PWV (∆ = 0.38 m/s; 95% CI: 0.07, 0.69; ES = 0.5) and PWVmin (∆ = 0.16 m/s; 95% CI: 0.05, 0.28; ES = 0.6). There was a large intra-individual (pre- vs post-endothelial dysfunction) association between FMD and PWVmin (r = -0.61; 95% CI: -0.82, -0.24). In conclusion, acute change in PWV and PWVmin are at least partially driven by changes in endothelial function.

New Zealand Blackcurrant Extract Enhances Muscle Oxygenation During Forearm Exercise in Intermediate-Level Rock Climbers.

The delivery to and utilization of oxygenated hemoglobin to the forearm muscles are key determinants of rock-climbing performance. Anthocyanin-rich New Zealand blackcurrant (NZBC) has been suggested to improve blood flow and may enhance forearm endurance performance. As such, a double-blind, randomized crossover design study with 12 participants performed submaximal intermittent contractions (at 40% maximal voluntary contraction) to failure after a 7-day intake of 600 mg/day NZBC extract or placebo. Minimum tissue saturation index (TSI%) was assessed during the contractions. During recovery, time to half recovery of TSI% and brachial artery blood flow were assessed. There was no difference in time to exhaustion between NZBC and placebo. Minimum TSI% was lower with NZBC extract (43 ± 8 vs. 50 ± 11 TSI%; p = .007; Cohen's d = 1.01). During recovery, there was no effect on brachial artery blood flow. However, time to half recovery was faster with NZBC (26 ± 17 vs. 42 ± 26 s; p = .001; Cohen's d = 1.3) following exhaustive contractions. Seven days of NZBC extract appears to improve muscle oxygenation during and following contractions with no change in either arterial blood flow or forearm endurance performance.

Repeat Treatment With Rifaximin Is Safe and Effective in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.

BACKGROUND & AIMS: Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). A phase 3, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin. METHODS: The trial included adults with IBS-D, mean abdominal pain and bloating scores of 3 or more, and loose stool, located at 270 centers in the United States and Europe from February 2012 through June 2014. Those responding to a 2-week course of open-label rifaximin 550 mg 3 times daily, who then relapsed during an observation phase (up to 18 weeks), were randomly assigned to groups given repeat treatments of rifaximin 550 mg or placebo 3 times daily for 2 weeks. The primary end point was percentage of responders after first repeat treatment, defined as a decrease in abdominal pain of ≥30% from baseline and a decrease in frequency of loose stools of ≥50% from baseline, for 2 or more weeks during a 4-week post-treatment period. RESULTS: Of 1074 patients (44.1%) who responded to open-label rifaximin, 382 (35.6%) did not relapse and 692 (64.4%) did; of these, 636 were randomly assigned to receive repeat treatment with rifaximin (n = 328) or placebo (n = 308). The percentage of responders was significantly greater with rifaximin than placebo (38.1% vs 31.5%; P = .03). The percentage of responders for abdominal pain (50.6% vs 42.2%; P = .018) was significantly greater with rifaximin than placebo, but not stool consistency (51.8% vs 50.0%; P = .42). Significant improvements were also noted for prevention of recurrence, durable response, and bowel movement urgency. Adverse event rates were low and similar between groups. CONCLUSIONS: In a phase 3 study of patients with relapsing symptoms of IBS-D, repeat rifaximin treatment was efficacious and well tolerated. ClinicalTrials.gov ID: NCT01543178.

Budesonide foam induces remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis.

BACKGROUND & AIMS: Budesonide is a high-potency, second-generation corticosteroid designed to minimize systemic adverse consequences of conventional corticosteroids. We performed 2 randomized, phase 3 trials to evaluate the ability of budesonide rectal foam, formulated to optimize retention and provide uniform delivery of budesonide to the rectum and distal colon, to induce remission in patients with ulcerative proctitis or ulcerative proctosigmoiditis. METHODS: Two identically designed, randomized, double-blind, placebo-controlled trials evaluated the efficacy of budesonide foam for induction of remission in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis who received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo. RESULTS: Remission at week 6 occurred significantly more frequently among patients receiving budesonide foam than placebo (Study 1: 38.3% vs 25.8%; P = .0324; Study 2: 44.0% vs 22.4%; P < .0001). A significantly greater percentage of patients receiving budesonide foam vs placebo achieved rectal bleeding resolution (Study 1: 46.6% vs 28.0%; P = .0022; Study 2: 50.0% vs 28.6%; P = .0002) and endoscopic improvement (Study 1: 55.6% vs 43.2%; P = .0486; Study 2: 56.0% vs 36.7%; P = .0013) at week 6. Most adverse events occurred at similar frequencies between groups, although events related to changes in cortisol values were reported more frequently with budesonide foam. There were no cases of clinically symptomatic adrenal insufficiency. CONCLUSIONS: Budesonide rectal foam was well tolerated and more efficacious than placebo in inducing remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. ClinicalTrials.gov ID: NCT01008410 and NCT01008423.

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

GOALS: To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. BACKGROUND: Mesalamine is a first-line treatment for induction and maintenance of UC remission. STUDY: A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. RESULTS: A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. CONCLUSIONS: Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission.

BACKGROUND: Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. AIMS: Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. METHODS: Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. RESULTS: Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. CONCLUSIONS: MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

Efficacy and Tolerability of Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: A Responder Analysis of 2 Randomized, Placebo-Controlled Trials.

BACKGROUND: Subcutaneous methylnaltrexone is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); factors determining optimal responsiveness to OIC treatment, however, have not been elucidated. This post hoc responder analysis examined the influence of demographic and baseline characteristics on methylnaltrexone efficacy and tolerability in this population. METHODS: Data were pooled from 2 randomized, double-blind, placebo-controlled, phase 3 studies of subcutaneous methylnaltrexone (0.15 and 0.30 mg/kg) [ClinicalTrials.gov identifiers: Study 301 - NCT00401362; Study 302 - NCT00402038]. Subgroup analyses of the primary outcome, percentage of patients with rescue medication-free bowel movements (RFBM) within 4 hours of first dose, were conducted for age, sex, primary diagnosis, baseline constipation-related distress score, and baseline oral morphine equivalent dose. RESULTS: More than 50% of 165 patients treated with either methylnaltrexone dose experienced a RFBM within 4 hours vs. 14.6% of 123 placebo-treated patients (P < 0.0001 for both methylnaltrexone doses vs. placebo). Methylnaltrexone response was significantly greater than placebo response in all subgroups (P < 0.01). The largest differences vs. placebo were observed for patients taking methylnaltrexone 0.30 mg/kg with a noncancer primary diagnosis (70.0% [methylnaltrexone] vs. 12.8% [placebo]; P < 0.001) and for patients taking methylnaltrexone 0.30 mg/kg maintained on ≥ 150 mg/day baseline morphine equivalent doses (73.3% vs. 16.7%; P < 0.0001). Common adverse events were abdominal pain (pooled methylnaltrexone: 27.9%, placebo: 9.8%), flatulence (13.3%, 5.7%), and nausea (10.9%, 4.9%). Tolerability was comparable across subgroups. CONCLUSION: Subcutaneous methylnaltrexone provides a rapid, robust, and consistent RFBM response in patients with advanced illness and OIC. Methylnaltrexone 0.30 mg/kg may elicit particularly favorable responses in select patient populations.

The Effect of Sitting Duration on Peripheral Blood Pressure Responses to Prolonged Sitting, With and Without Interruption: A Systematic Review and Meta-Analysis.

BACKGROUND: A previous meta-analysis reported that: (i) an acute bout of prolonged uninterrupted sitting induces a significant increase in peripheral blood pressure (BP) and (ii) the increase in BP can be offset by interrupting the sitting bout with light aerobic activities such as walking. However, the temporal association between prolonged uninterrupted sitting and BP was not determined. A better understanding of temporality, for example, how long it takes BP to increase, will assist in prescribing sitting interruption strategies. OBJECTIVES: We aimed to determine: (1) the temporal association between the duration of uninterrupted sitting and BP and (2) whether regular sitting interruptions moderate the association between uninterrupted sitting and BP. DATA SOURCES: Electronic databases (PubMed, Web of Science, SPORTDiscus) were searched from inception to July 2022. Reference lists of eligible studies and relevant reviews were also screened. STUDY SELECTION: Inclusion criteria for objective (1) were: (i) participants aged ≥ 18 years; (ii) a prolonged sitting bout ≥ 1 h; and (iii) peripheral BP measurements (systolic BP, diastolic BP, and/or mean arterial pressure) at more than two timepoints during the sitting bout. Additional criteria for objective (2) were: (i) the sitting interruption strategy was implemented during the sitting bout (i.e., not prior to engaging in sitting) and (ii) the study included a control (uninterrupted sitting) condition or group. APPRAISAL AND SYNTHESIS METHODS: There were 1555 articles identified, of which 33 met inclusion criteria for objective (1). Of those articles, 20 met inclusion criteria for objective (2). To investigate the effect of sitting duration on the BP response, unstandardized b coefficients (mmHg/h) and 95% confidence intervals (CIs) were calculated using a three-level mixed-effect meta-regression. RESULTS: Increased sitting duration was positively associated with systolic BP (b = 0.42 mmHg/h, 95% CI 0.18-0.60), diastolic BP (b = 0.24 mmHg/h, 95% CI 0.06-0.42), and mean arterial pressure (b = 0.66 mmHg/h, 95% CI 0.36-0.90). In trials where sitting was interrupted, there was a significant decrease in systolic BP (b = - 0.24 mmHg/h, 95% CI - 0.42 to - 0.06) and diastolic BP (b = - 0.24 mmHg/h, 95% CI - 0.42 to - 0.12), and a non-significant change in mean arterial pressure (p = 0.69). CONCLUSIONS: Increased uninterrupted sitting duration results in greater increases in BP; however, regularly interrupting sitting may offset negative effects.

The effect of cardiorespiratory fitness and habitual physical activity on cardiovascular responses to 2 h of uninterrupted sitting.

Prolonged uninterrupted sitting of >3 h has been shown to acutely cause central and peripheral cardiovascular dysfunction. However, individuals rarely sit uninterrupted for >2 h, and the cardiovascular response to this time is currently unknown. In addition, while increased cardiorespiratory fitness (CRF) and habitual physical activity (HPA) are independently associated with improvements in central and peripheral cardiovascular function, it remains unclear whether they influence the response to uninterrupted sitting. This study sought to 1) determine whether 2 h of uninterrupted sitting acutely impairs carotid-femoral pulse wave velocity (cfPWV), femoral ankle PWV (faPWV), and central and peripheral blood pressure and 2) investigate the associations between CRF and HPA versus PWV changes during uninterrupted sitting. Following 2 h of uninterrupted sitting, faPWV significantly increased [mean difference (MD) = 0.26 m·s-1, standard error (SE) = 0.10, P = 0.013] as did diastolic blood pressure (MD = 2.83 mmHg, SE = 1.08, P = 0.014), however, cfPWV did not significantly change. Although our study shows 2 h of uninterrupted sitting significantly impairs faPWV, neither CRF (r = 0.105, P = 0.595) nor HPA (r = -0.228, P = 0.253) was associated with the increases.NEW & NOTEWORTHY We demonstrate that neither cardiorespiratory fitness nor habitual physical activity influence central and peripheral cardiovascular responses to a 2-h bout of uninterrupted sitting in healthy young adults.

Determination of Optimal Eosinophil Thresholds for Diagnosis of Eosinophilic Gastritis and Duodenitis: A Pooled Analysis of 4 Prospective Studies.

INTRODUCTION: Consensus is lacking regarding the number of eosinophils (eos) required for the diagnosis of eosinophilic gastritis (EoG) and eosinophilic duodenitis (EoD). In addition, thresholds that require multiple high-power fields (HPFs) may not be practical for clinical use, resulting in delayed or missed diagnoses. This pooled analysis of 4 prospective studies assessed thresholds for multiple and single HPFs used to diagnose EoG and EoD. METHODS: Studies included the phase 2 ENIGMA1, the phase 3 ENIGMA2, an EoG/EoD prevalence study and a healthy volunteer study. Eos were quantified in the epithelium and lamina propria for controls and symptomatic participants. Symptomatic participants were further divided by histologic diagnosis of EoG/EoD. Peak eos counts were assessed, and the area under the receiver operating characteristic curve was analyzed to identify eos cutoffs for detection of EoG/EoD using the Youden index and sensitivity and specificity equality approaches. RESULTS: Based on the highest specificity analysis in 740 patients, the optimal eos threshold was determined to be 20 eos/HPF in 5 gastric HPFs for EoG (71% sensitivity and 94% specificity) and 33 eos/HPF in 3 duodenal HPFs for EoD (49% sensitivity and 100% specificity). For single-field analysis, the optimal eos thresholds were 33 eos/HPF (EoG) and 37 eos/HPF (EoD), both corresponding to 93% sensitivity and 93% specificity. DISCUSSION: Highly specific single gastric and duodenal HPF thresholds may have more clinical applicability than thresholds requiring multiple HPFs and could better facilitate development of practical histopathologic guidelines to aid pathologists and clinicians in the detection and diagnosis of EoG and/or EoD.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background: Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion: It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study.

BACKGROUND: HIV-associated diarrhea remains a significant concern with limited treatment options. OBJECTIVE: To determine the optimal dose, efficacy, and safety of crofelemer for noninfectious diarrhea. METHODS: This randomized, double-blind, phase 3 trial used a 2-stage design. Both stages included 2-week screening, 4-week placebo-controlled treatment, and 20-week placebo-free (open-label) extension phases. In stage I, 196 HIV-seropositive patients with chronic diarrhea were randomized to crofelemer 125 mg, 250 mg, or 500 mg or placebo twice daily. Using a prospective analysis, the 125-mg twice-daily dose was selected for stage II. In stage II, 180 new patients were randomized to crofelemer 125 mg twice daily or placebo for 4 weeks. Primary efficacy analysis was the percentage of patients (stages I/II combined) who achieved clinical response (defined as ≤2 watery stools/week during ≥2 of 4 weeks). During the placebo-free extension phase, response (≤2 watery stools) was assessed weekly. RESULTS: Significantly more patients receiving crofelemer 125 mg achieved clinical response versus placebo (17.6% vs 8.0%; one-sided, P = .01). Crofelemer 125 mg resulted in a greater change from baseline in number of daily watery bowel movements (P = .04) and daily stool consistency score (P = .02) versus placebo. During the placebo-free extension phase, percentages of weekly responders ranged from 40% to 56% at weeks 11 to 24. Crofelemer was minimally absorbed, well tolerated, did not negatively impact clinical immune parameters, and had a safety profile comparable to placebo. CONCLUSIONS: In HIV-seropositive patients taking stable antiretroviral therapy, crofelemer provided significant improvement in diarrhea with a favorable safety profile.

Association between Yoga Participation and Arterial Stiffness: A Cross-Sectional Study.

BACKGROUND: Yoga may help adults of all fitness levels increase their physical activity and decrease their cardiovascular disease risk. AIM: To determine if arterial stiffness is lower (beneficial) in yoga versus non-yoga participants. METHOD: This cross-sectional study included 202 yoga (48.4 + 14.1 years, 81% female) and 181 (42.8 + 14.1 years, 44% female) non-yoga participants. The primary outcome was carotid-femoral pulse wave velocity (cfPWV). The two groups were compared using analysis of covariance with adjustments for demographic (age and sex), hemodynamic (mean arterial pressure and heart rate), lifestyle (physical activity levels, sedentary behaviour, smoking status and perceived stress score) and cardiometabolic (waist-to-hip ratio, total cholesterol and fasting glucose) factors. RESULTS: Following adjustments, cfPWV was significantly lower in yoga compared to non-yoga participants with a mean difference: -0.28 m.s-1, (95% CI = -0.55 to 0.08). CONCLUSION: At a population level, yoga participation may assist with decreasing the risk of cardiovascular disease in adults.

Localized activity attenuates the combined impact of a high fat meal and prolonged sitting on arterial stiffness: A randomized, controlled cross-over trial.

Exposure to acute prolonged sitting and consumption of a high fat (HF) meal have been shown to independently and additively impair central and peripheral cardiovascular function. This study sought to determine whether localized activity, namely leg fidgeting, offers a protective effect to these deleterious effects. Using a randomized crossover design with three trials, 18 healthy males sat uninterrupted for 180 min following the consumption of a low fat (LF, trial 1) or HF meal (trial 2). The third trial consisted of a HF meal but sitting was interrupted with 1 min of leg fidgeting (isolated bilateral plantar flexion) consisting of -250 taps per min every 5 min for the 180 min duration. Carotid-femoral pulse wave velocity (cfPWV), aortic-femoral stiffness gradient (af-SG), superficial femoral blood flow, shear-rate and PWVß, triglyceride concentrations and lower-limb venous pooling (HHb) were assessed pre and post sitting in all trials. General linear mixed model found that following the uninterrupted HF trial, there was a significant worsening of cfPWV (mean difference (MD) = 0.57 mˑs-1; d = 1.04) and the af-SG (MD = 0.14, d = 0.50), and femoral artery blood flow (MD = 18 mlˑmin-1; d = 0.48) and shear rate (MD = 15 S1; d = 0.67) decreased. However, leg fidgeting was enough to prevent the combined deleterious effects of prolonged sitting following a HF meal. As there were no significant changes in the LF trial, the HF meal maybe the predominant driver when uninterrupted sitting is combined with a HF meal.