Clinical predictive value of renalase in post-ERCP pancreatitis.

BACKGROUND AND AIMS: Plasma levels of renalase decrease in acute experimental pancreatitis. We aimed to determine if decreases in plasma renalase levels after ERCP predict the occurrence of post-ERCP pancreatitis (PEP). METHODS: In this prospective cohort study conducted at a tertiary hospital, plasma renalase was determined before ERCP (baseline) and at 30 and 60 minutes after ERCP. Native renalase levels, acidified renalase, and native-to-acidified renalase proportions were analyzed over time using a longitudinal regression model. RESULTS: Among 273 patients, 31 developed PEP. Only 1 PEP patient had a baseline native renalase >6.0 µg/mL, whereas 38 of 242 without PEP had a native renalase > 6.0 µg/mL, indicating a sensitivity of 97% (30/31) and specificity of 16% (38/242) in predicting PEP. Longitudinal models did not show differences over time between groups. CONCLUSIONS: Baseline native renalase levels are very sensitive for predicting PEP. Further studies are needed to determine the potential clinical role of renalase in predicting and preventing PEP.

A scaled kernel density estimation prior for dynamic borrowing of historical information with application to clinical trial design.

Incorporating historical data into a current data analysis can improve estimation of parameters shared across both datasets and increase the power to detect associations of interest while reducing the time and cost of new data collection. Several methods for prior distribution elicitation have been introduced to allow for the data-driven borrowing of historical information within a Bayesian analysis of the current data. We propose scaled Gaussian kernel density estimation (SGKDE) prior distributions as potentially more flexible alternatives. SGKDE priors directly use posterior samples collected from a historical data analysis to approximate probability density functions, whose variances depend on the degree of similarity between the historical and current datasets, which are used as prior distributions in the current data analysis. We compare the performances of the SGKDE priors with some existing approaches using a simulation study. Data from a recently completed phase III clinical trial of a maternal vaccine for respiratory syncytial virus are used to further explore the properties of SGKDE priors when designing a new clinical trial while incorporating historical data. Overall, both studies suggest that the new approach results in improved parameter estimation and power in the current data analysis compared to the considered existing methods.

Unresolved issues with noninferiority pragmatic trials: Results of a literature survey.

BACKGROUND: Issues with specification of margins, adherence, and analytic population can potentially bias results toward the alternative in randomized noninferiority pragmatic trials. To investigate this potential for bias, we conducted a targeted search of the medical literature to examine how noninferiority pragmatic trials address these issues. METHODS: An Ovid MEDLINE database search was performed identifying publications in New England Journal of Medicine, Journal of the American Medical Association, Lancet, or British Medical Journal published between 2015 and 2021 that included the words "pragmatic" or "comparative effectiveness" and "noninferiority" or "non-inferiority." Our search identified 14 potential trials, 12 meeting our inclusion criteria (11 individually randomized, 1 cluster-randomized). RESULTS: Eleven trials had results that met the criteria established for noninferiority. Noninferiority margins were prespecified for all trials; all but two trials provided justification of the margin. Most trials did some monitoring of treatment adherence. All trials conducted intent-to-treat or modified intent-to-treat analyses along with per-protocol analyses and these analyses reached similar conclusions. Only two trials included all randomized participants in the primary analysis, one used multiple imputation for missing data. The percentage excluded from primary analyses ranged from ∼2% to 30%. Reasons for exclusion included randomization in error, nonadherence, not receiving assigned treatment, death, withdrawal, lost to follow-up, and incomplete data. CONCLUSION: Specification of margins, adherence, and analytic population require careful consideration to prevent bias toward the alternative in noninferiority pragmatic trials. Although separate guidance has been developed for noninferiority and pragmatic trials, it is not compatible with conducting a noninferiority pragmatic trial. Hence, these trials should probably not be done in their current format without developing new guidelines.

Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death.

BACKGROUND & AIMS: Coronavirus-19 disease (COVID-19) is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (eg, ischemia, hyperinflammatory, or hypercoagulable states), and whether it can result in liver failure and death. METHODS: There were 834 consecutive patients hospitalized with COVID-19 who were included. Clinical, medication, and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an aspartate aminotransferase (AST) level 5 or more times the upper limit of normal; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyperinflammatory state was defined as high-sensitivity C-reactive protein value of 100 mg/L or more, and hypercoagulability was defined as D-dimer 5 mg/L or more at any time during hospitalization. RESULTS: A total of 105 (12.6%) patients developed significant liver injury. Compared with patients without significant liver injury, ischemia (odds ratio [OR], 4.3; range, 2.5-7.4; P < .0001) and tocilizumab use (OR, 3.6; range, 1.9-7.0; P = .0001) were independent predictors of significant liver injury. Although AST correlated closely with alanine aminotransferase (R = 0.89) throughout hospitalization, AST did not correlate with the international normalized ratio (R = 0.10) or with bilirubin level (R = 0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death (OR, 1.4; range, 0.8-2.6; P = .2), while ischemic (OR, 2.4; range, 1.4-4.0; P = .001), hypercoagulable (OR, 1.7; range, 1.1-2.6; P = .02), and hyperinflammatory (OR, 1.9; range, 1.2-3.1; P = .02) disease states were significant predictors of death. CONCLUSIONS: Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.

Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network.

BACKGROUND AND AIMS: The coronavirus-19 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 virus, is associated with significant morbidity and mortality attributable to pneumonia, acute respiratory distress syndrome, and multiorgan failure. Liver injury has been reported as a nonpulmonary manifestation of COVID-19, but characterization of liver test abnormalities and their association with clinical outcomes is incomplete. APPROACH AND RESULTS: We conducted a retrospective cohort study of 1,827 patients with confirmed COVID-19 who were hospitalized within the Yale-New Haven Health System between March 14, 2020 and April 23, 2020. Clinical characteristics, liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], total bilirubin [TBIL], and albumin) at three time points (preinfection baseline, admission, and peak hospitalization), and hospitalization outcomes (severe COVID-19, intensive care unit [ICU] admission, mechanical ventilation, and death) were analyzed. Abnormal liver tests were commonly observed in hospitalized patients with COVID-19, both at admission (AST 66.9%, ALT 41.6%, ALP 13.5%, and TBIL 4.3%) and peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, and TBIL 16.1%). Most patients with abnormal liver tests at admission had minimal elevations 1-2× the upper limit of normal (ULN; AST 63.7%, ALT 63.5%, ALP 80.0%, and TBIL 75.7%). A significant proportion of these patients had abnormal liver tests prehospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, and TBIL 44.4%). Multivariate analysis revealed an association between abnormal liver tests and severe COVID-19, including ICU admission, mechanical ventilation, and death; associations with age, male sex, body mass index, and diabetes mellitus were also observed. Medications used in COVID-19 treatment (lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab) were associated with peak hospitalization liver transaminase elevations >5× ULN. CONCLUSIONS: Abnormal liver tests occur in most hospitalized patients with COVID-19 and may be associated with poorer clinical outcomes.

Material hardship is associated with posttraumatic stress disorder symptoms among low-income Black women.

The link between socioeconomic status and posttraumatic stress disorder (PTSD) symptoms is well established. Given that Black women are disproportionately burdened by both poverty and PTSD symptoms, research focusing on these constructs among this population is needed. The current study assessed the association between material hardship (i.e., difficulty meeting basic needs) and PTSD symptoms among 227 low-income Black women in the United States. We explored several potential explanations for the association between poverty and PTSD symptoms (e.g., individuals living in poverty may experience higher levels of trauma exposure; individuals living in poverty may have less access to relevant protective resources, like social support; poverty itself may represent a traumatic stressor). Using robust negative binomial regression, a positive association between material hardship and PTSD symptoms emerged, B = 0.10, p = .009, SMD = 0.08. When trauma exposure was added to the model, it was positively associated with PTSD symptoms, B = 0.18, p < .001, SMD = 0.16, and material hardship remained positively associated with PTSD symptoms, B = 0.10, p =.019, SMD = 0.08. When social support indicators were added to the model, they were not associated with PTSD symptoms; however, material hardship remained significantly associated, B = 0.10, p = .021, SMD = 0.08. In the model with material hardship and trauma exposure, a significant interaction between material hardship and trauma exposure on PTSD symptoms emerged, B = -0.04, p = .027. These results demonstrate the importance of including material hardship in trauma research, assessment, and treatment.

Associations Among Increases in Posttraumatic Stress Symptoms, Neurocognitive Performance, and Long-Term Functional Outcomes in U.S. Iraq War Veterans.

Cross-sectional research suggests that posttraumatic stress symptoms (PTSS) among war zone veterans are associated with functional impairment and poor quality of life. Less is known about the long-term functional repercussions of PTSS. This study of Iraq War veterans examined the associations between increases in PTSS and long-term functional outcomes, including the potential contributions of neurocognitive decrements. Service members and veterans (N = 594) completed self-report measures of functioning and PTSS severity before Iraq War deployment and again after their return (M = 9.3 years postdeployment). Some participants (n = 278) also completed neurocognitive testing at both times. Multiple regression analyses with the full sample-adjusted for TBI, demographic characteristics, military variables, and predeployment PTSS and functioning-revealed that increased PTSS severity over time was significantly associated with unemployment, aOR = 1.04, 95% CI [1.03, 1.06]; poorer work performance; and poorer physical, emotional, and cognitive health-related functioning at long-term follow-up, f2 s = 0.37-1.79. Among participants who completed neurocognitive testing, a decline in select neurocognitive measures was associated with poorer functioning; however, neurocognitive decrements did not account for associations between increased PTSS and unemployment, aOR = 1.04, 95% CI [1.02, 1.07], with the size and direction upheld after adding neurocognitive variables, or poorer functional outcomes, with small increases after adding neurocognitive measures to the models, f2 s = 0.03-0.10. War zone veterans experiencing long-term increased PTSS and/or neurocognitive decrements may be at elevated risk for higher-level functional impairment over time, suggesting that early PTSS management may enhance long-term functioning.

Retention in HIV care during the 3 years following release from incarceration: A cohort study.

BACKGROUND: Sustained retention in HIV care (RIC) and viral suppression (VS) are central to US national HIV prevention strategies, but have not been comprehensively assessed in criminal justice (CJ) populations with known health disparities. The purpose of this study is to identify predictors of RIC and VS following release from prison or jail. METHODS AND FINDINGS: This is a retrospective cohort study of all adult people living with HIV (PLWH) incarcerated in Connecticut, US, during the period January 1, 2007, to December 31, 2011, and observed through December 31, 2014 (n = 1,094). Most cohort participants were unmarried (83.7%) men (77.0%) who were black or Hispanic (78.1%) and acquired HIV from injection drug use (72.6%). Prison-based pharmacy and custody databases were linked with community HIV surveillance monitoring and case management databases. Post-release RIC declined steadily over 3 years of follow-up (67.2% retained for year 1, 51.3% retained for years 1-2, and 42.5% retained for years 1-3). Compared with individuals who were not re-incarcerated, individuals who were re-incarcerated were more likely to meet RIC criteria (48% versus 34%; p < 0.001) but less likely to have VS (72% versus 81%; p = 0.048). Using multivariable logistic regression models (individual-level analysis for 1,001 individuals after excluding 93 deaths), both sustained RIC and VS at 3 years post-release were independently associated with older age (RIC: adjusted odds ratio [AOR] = 1.61, 95% CI = 1.22-2.12; VS: AOR = 1.37, 95% CI = 1.06-1.78), having health insurance (RIC: AOR = 2.15, 95% CI = 1.60-2.89; VS: AOR = 2.01, 95% CI = 1.53-2.64), and receiving an increased number of transitional case management visits. The same factors were significant when we assessed RIC and VS outcomes in each 6-month period using generalized estimating equations (for 1,094 individuals contributing 6,227 6-month periods prior to death or censoring). Additionally, receipt of antiretroviral therapy during incarceration (RIC: AOR = 1.33, 95% CI 1.07-1.65; VS: AOR = 1.91, 95% CI = 1.56-2.34), early linkage to care post-release (RIC: AOR = 2.64, 95% CI = 2.03-3.43; VS: AOR = 1.79; 95% CI = 1.45-2.21), and absolute time and proportion of follow-up time spent re-incarcerated were highly correlated with better treatment outcomes. Limited data were available on changes over time in injection drug use or other substance use disorders, psychiatric disorders, or housing status. CONCLUSIONS: In a large cohort of CJ-involved PLWH with a 3-year post-release evaluation, RIC diminished significantly over time, but was associated with HIV care during incarceration, health insurance, case management services, and early linkage to care post-release. While re-incarceration and conditional release provide opportunities to engage in care, reducing recidivism and supporting community-based RIC efforts are key to improving longitudinal treatment outcomes among CJ-involved PLWH.

Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men.

BACKGROUND & AIMS: Bowel preparation is defined as adequate if it is sufficient for identification of polyps greater than 5 mm. However, adequate preparation has not been quantified. We performed a prospective observational study to provide an objective definition of adequate preparation, based on the Boston Bowel Prep Scale (BBPS, which consists of 0-3 points for each of 3 colon segments). METHODS: We collected data from 438 men who underwent screening or surveillance colonoscopies and then repeat colonoscopy examinations within 60 days by a different blinded endoscopist (1161 colon segments total) at the West Haven Veterans Affairs Medical Center from January 2014 to February 2015. Missed polyps were defined as those detected on the second examination of patients with the best possible bowel preparation (colon segment BBPS score of 3) on the second examination. The primary outcome was the proportion of colon segments with adenomas larger than 5 mm that were missed in the first examination. We postulated that the miss rate was noninferior for segments with BBPS scores of 2 vs those with BBPS scores of 3 (noninferiority margin, <5%). Our secondary hypotheses were that miss rates were higher in segments with BBPS scores of 1 vs those with scores of 3 or of 2. RESULTS: The adjusted proportion with missed adenomas greater than 5 mm was noninferior for segments with BBPS scores of 2 (5.2%) vs those with BBPS scores of 3 (5.6%) (a difference of -0.4%; 95% confidence interval [CI], -2.9% to 2.2%). Of study subjects, 347 (79.2%) had BBPS scores of 2 or greater in all segments on the initial examination. A higher proportion of segments with BBPS scores of 1 had missed adenomas larger than 5 mm (15.9%) than segments with BBPS scores of 3 (5.6%) (a difference of 10.3%; 95% CI, 2.7%-17.9%) or 2 (5.2%) (a difference of 10.7%; 95% CI, 3.2%-18.1%). Screening and surveillance intervals based solely on the findings at the first examination would have been incorrect for 16.3% of patients with BBPS scores of 3 in all segments, for 15.3% with BBPS scores of 2 or 3 in all segments, and for 43.5% of patients with a BBPS score of 1 in 1 or more segments. CONCLUSIONS: Patients with BBPS scores of 2 or 3 for all colon segments have adequate bowel preparation for the detection of adenomas larger than 5 mm and should return for screening or surveillance colonoscopy at standard guideline-recommended intervals. Colon segments with a BBPS score of 1 have a significantly higher rate of missed adenomas larger than 5 mm than segments with scores of 2 or 3. This finding supports a recommendation for early repeat colonoscopic evaluation in patients with a BBPS score of 0 or 1 in any colon segment.

Effect of Intragastric Balloons on Liver Enzymes: A Systematic Review and Meta-Analysis.

BACKGROUND: Intragastric balloons (IGBs) are safe and effective in inducing weight loss in obese patients. The objective of this study was to review and analyze the available data of the effect of IGB on markers of nonalcoholic fatty liver disease (NAFLD) and liver enzymes. METHODS: Searches were performed of MEDLINE and Embase databases from inception through January 2016. Study inclusion criteria were the following: ≥5 overweight or obese adult patients undergoing intragastric balloon placement, with liver tests [alanine aminotransferase (ALT) or gamma-glutamyl transpeptidase (GGT)] or markers of NAFLD (e.g., imaging, biopsy) reported before balloon insertion and after balloon removal at 6 months. RESULTS: Nine observational studies and one randomized trial were identified. ALT decreased by -10.02 U/l (95 % CI, -13.2, -6.8), GGT decreased by -9.82 U/l (95 % CI, -12.9, -6.8), and BMI decreased by -4.98 kg/m(2) (-5.6, -4.4) with IGB therapy. Hepatic steatosis improved from baseline after 6 months of balloon therapy by magnetic resonance imaging (fat fraction, 16.7 ± 10.9-7.6 ± 9.8, p = 0.003), ultrasound (severe liver steatosis, 52-4 %, p < 0.0001). Histological NAFLD activity score was lower after 6 months of IGB versus control with sham endoscopy and diet (2 ± 0.75 vs. 4 ± 2.25, p = 0.03). CONCLUSION: The use of intragastric balloon decreases liver enzymes and is potentially an effective short-term treatment for NAFLD as part of a multidisciplinary approach. Larger, more rigorous trials are needed to confirm the effect of IGBs on NAFLD.

Can a Computerized Simulator Assess Skill Level and Improvement in Performance of ERCP?

BACKGROUND: Endoscopic retrograde cholangiography (ERCP) is a challenging procedure with considerable risk. Computerized simulators are valuable in training for flexible endoscopy, but little data exist for their use in ERCP training. AIM: To determine a simulator's ability to assess the level of ERCP skill and its responsiveness over time to increasing trainee experience. MATERIALS AND METHODS: In this prospective parallel-arm cohort study, six novice gastroenterology fellows and four gastroenterology faculty with expertise in ERCP completed four simulated baseline cases and the same four cases at a later date. This study took place at a surgical skills center at an academic tertiary referral center. The primary outcome was the total time to complete the ERCP procedure. RESULTS: For the baseline session, experts had a shorter total procedure time than novices (444.0 vs. 616.9 s; least squares mean; p = 0.026). There was no significant difference between experts and novices in the difference of total procedure time between session 1 and session 2 (-200.3 vs. -164.4; least squares mean; p = 0.402). CONCLUSIONS: The simulator was able to differentiate experts from novices for the primary outcome of total procedure time. The simulator was not responsive to an increase in trainee experience over time.

Selection of the effect size for sample size determination for a continuous response in a superiority clinical trial using a hybrid classical and Bayesian procedure.

BACKGROUND: When designing studies that have a continuous outcome as the primary endpoint, the hypothesized effect size ([Formula: see text]), that is, the hypothesized difference in means ([Formula: see text]) relative to the assumed variability of the endpoint ([Formula: see text]), plays an important role in sample size and power calculations. Point estimates for [Formula: see text] and [Formula: see text] are often calculated using historical data. However, the uncertainty in these estimates is rarely addressed. METHODS: This article presents a hybrid classical and Bayesian procedure that formally integrates prior information on the distributions of [Formula: see text] and [Formula: see text] into the study's power calculation. Conditional expected power, which averages the traditional power curve using the prior distributions of [Formula: see text] and [Formula: see text] as the averaging weight, is used, and the value of [Formula: see text] is found that equates the prespecified frequentist power ([Formula: see text]) and the conditional expected power of the trial. This hypothesized effect size is then used in traditional sample size calculations when determining sample size for the study. RESULTS: The value of [Formula: see text] found using this method may be expressed as a function of the prior means of [Formula: see text] and [Formula: see text], [Formula: see text], and their prior standard deviations, [Formula: see text]. We show that the "naïve" estimate of the effect size, that is, the ratio of prior means, should be down-weighted to account for the variability in the parameters. An example is presented for designing a placebo-controlled clinical trial testing the antidepressant effect of alprazolam as monotherapy for major depression. CONCLUSION: Through this method, we are able to formally integrate prior information on the uncertainty and variability of both the treatment effect and the common standard deviation into the design of the study while maintaining a frequentist framework for the final analysis. Solving for the effect size which the study has a high probability of correctly detecting based on the available prior information on the difference [Formula: see text] and the standard deviation [Formula: see text] provides a valuable, substantiated estimate that can form the basis for discussion about the study's feasibility during the design phase.

Influence of colonoscopy quality measures on patients' colonoscopist selection.

OBJECTIVES: The Affordable Care Act emphasizes the use of quality metrics and greater patient understanding of health-care options and access to physician performance data. The objectives of this study were to determine patients' familiarity with colonoscopy quality measures (CQMs) and their influence on patient selection of a colonoscopist. METHODS: A prospective survey of patients before screening or surveillance colonoscopy at university hospital, community hospital, and ambulatory procedure center endoscopy units was performed from 2011 to 2012. RESULTS: Among the 417 participants, 20% (85/417) researched their physician's rating. The rates of familiarity with CQM were 88 % (353/402) for adequate bowel preparation, 30% (118/398) for adenoma detection rate (ADR), 26% (102/397) for cecal intubation rate, and 21% (82/394) for greater-than-6-min withdrawal time. Ninety-six percent (366/386) believed that colonoscopists' reporting of ADR to other physicians was important or very important. In selecting a colonoscopist, primary care provider referral was ranked as the first or second-most important of four factors in 87% (339/391). Even among patients who responded "it is very important" to report CQM to other doctors and patients, none ranked CQM as the most important factor in selecting a colonoscopist. CONCLUSIONS: Patient awareness of CQM, other than adequate bowel preparation, was low. Quality measure reporting is important to patients, but primary care provider referral was the most important factor in colonoscopist selection. This suggests that primary care providers, as well as patients, are important to include in educational strategies regarding quality metrics.

A double-blind, randomized, sham-controlled trial of the effect of a radiation-attenuating drape on radiation exposure to endoscopy staff during ERCP.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with radiation exposure to the endoscopist and staff that may be significant in high-volume centers. We investigated whether a radiation-attenuating drape over the fluoroscopy image intensifier reduces radiation exposure during ERCP. METHODS: We performed a prospective, randomized, double-blind trial of 100 therapeutic ERCPs at a tertiary-care university center. Procedures were randomly assigned to groups receiving lead-free radiation-attenuating drapes (n=50) or identical sham drapes (n=50). The drapes were suspended around the fluoroscopy image intensifier during ERCP. The primary end point was the effective dose of radiation measured at the endoscopist's eye and neck, and at the assisting nurse's neck. The cumulative annual radiation exposure was also estimated. RESULTS: Fluoroscopy time, absorbed radiation dose, and dose area product were similar in the study groups. Mean effective dose for sham vs. radiation-attenuating drape was 0.21±0.27 vs. 0.02±0.02 mSv at the endoscopist's eye, 0.35±0.44 vs. 0.03±0.03 mSv at the endoscopist's neck, and 0.27±0.34 vs. 0.02±0.02 mSv at the nurse's neck (P<0.0001 for all comparisons). The relative risk reduction in radiation was 90%, 91%, and 93% at the three sites. At a high-volume center in which an endoscopist performs 500 therapeutic ERCPs per year, the estimated cumulative annual effective dose at the endoscopist's eye level is 126 mSv with conventional protection and 12 mSv with a radiation-attenuating drape, with the recommended limit being 20 mSv. CONCLUSIONS: The addition of a radiation-attenuating drape around the image intensifier during ERCP significantly decreases radiation exposure to endoscopists and staff by ∼90%.

Functional disability among older women with fecal incontinence.

OBJECTIVE: The prevalence of functional disability for basic activities of daily living (ADLs) in older women with fecal incontinence (FI) is not well characterized. Our objective was to determine the prevalence of functional disability among community-dwelling older women with FI. STUDY DESIGN: We conducted a secondary database analysis of the 2005-2006 National Social Life, Health and Aging Project, a cross-sectional study of community-dwelling older adults that had been conducted by single in-home interviews. FI was defined as an affirmative answer to the question, "Have you lost control of your bowels (stool incontinence or anal incontinence)?" with a frequency of "at least monthly." We then examined functional status. Women were asked about 7 basic ADLs. Statistical analyses with percentage estimates and 95% confidence intervals (CIs) were performed. RESULTS: We included 1412 women in our analysis. FI, at least monthly, was reported by 5.5% of community-dwelling older women (n = 77); 63.2% (95% CI, 50.1-76.4) of the women with FI reported difficulty or dependence with ≥1 ADLs, and 31.2% (95% CI, 18.9-43.6) of the women specifically reported difficulty or dependence with using the toilet. After adjustment for age category, race/ethnicity, education level, women with FI had 2.6 increased odds (95% CI, 1.26-5.35) of difficulty or dependence compared with women with no FI. Other significant risk factors for increased functional difficulty/dependence included obesity (body mass index, ≥30 kg/m(2)) and depressive symptoms. CONCLUSION: Consistent with other large epidemiologic studies, we found monthly FI was reported by 5.5% of older women (n/N = 77/1412). More than 60% of community-dwelling older women with FI report functional difficulty or dependence with ≥1 ADL and specifically; more than 30% of women with FI report difficulty or dependence using/reaching the toilet. Because of the high prevalence of functional disability in older women with FI, we purpose that initial evaluation and treatment of FI may be improved by considering functional status.

Upper esophageal sphincter abnormalities: frequent finding on high-resolution esophageal manometry and associated with poorer treatment response in achalasia.

BACKGROUND: Abnormalities of the upper esophageal sphincter (UES) on high-resolution esophageal manometry (HREM) have been observed in both symptomatic and asymptomatic individuals and are often interpreted as incidental findings of unclear clinical significance. AIMS: Our primary aims were: (1) to assess the frequency of UES abnormalities in consecutive patients referred for HREM studies; and (2) to characterize the demographics, clinical symptoms, and manometric profiles associated with UES abnormalities as compared with those with normal UES function. MATERIALS AND METHODS: We performed a retrospective study of 200 consecutive patients referred for HREM. Patients were divided into those with normal and abnormal UES function, including impaired relaxation (residual pressure >12 mm Hg), hypertensive (>104 mm Hg), and hypotensive (<34 mm Hg) resting pressure. Clinical and manometric profiles were compared. RESULTS: A total of 32.5% of patients had UES abnormalities, the majority of which were hypertensive (55.4%). Patients with achalasia were significantly more likely to have UES abnormalities as compared with normal UES function (57.2% vs. 42.9%, P=0.04), with the most frequent abnormality being a hypertensive UES (50%). In addition, patients with impaired lower esophageal sphincter (LES) relaxation (esophagogastric junction outflow obstruction or achalasia) were more likely to have an UES abnormality present as compared with those with normal LES relaxation (53.1% vs. 28.6%, P=0.01). When we assessed for treatment response among patients with achalasia, we found that subjects with evidence of UES dysfunction had significantly worse treatment outcomes as compared with those without UES abnormalities present (20% improved vs. 100%, P=0.015). This remained true even after adjusting for type of treatment received (surgical myotomy, per-oral endoscopic mytotomy, botulinum toxin injection, pneumatic dilatation, medical therapy, P=0.67) and achalasia subtype (P=1.00). CONCLUSIONS: UES abnormalities are a frequent finding on HREM studies, especially in patients with impaired LES relaxation, including both achalasia and esophagogastric junction outflow obstruction. Interestingly, the most common UES abnormality associated with achalasia was a hypertensive resting UES, despite the fact that achalasia is thought to spare striated muscle. Among patients with achalasia, we found a significant association between the lack of treatment response and the presence of UES dysfunction. The routine evaluation of UES function in patients referred for manometry may enhance our understanding of esophageal motility disorders and may yield important prognostic information, particularly in subjects with achalasia. Future prospective studies are needed to further delineate the underlying mechanism between UES dysfunction with achalasia and other esophageal motility disorders to predict treatment response and guide therapeutic treatment modalities.

Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth.

BACKGROUND: Altered small intestinal motility is thought to contribute to the development of small intestinal bacterial overgrowth (SIBO). The clinical manifestations of SIBO and consequent malabsorption are wide ranging and include abdominal pain, bloating, diarrhea, weight loss, and nutritional deficiencies. However, due to the nonspecific nature of symptoms, the diagnosis may often be overlooked. To date, few studies have illustrated a direct relationship between impaired small intestinal motility and SIBO. In addition, further study has been limited by the technical challenges and lack of widespread availability of antroduodenal manometry. The development of a wireless motility capsule (WMC) (SmartPill) that evaluates pressure, pH, and temperature throughout the GI tract offers the potential to identify patients with small bowel transit delays who may be at risk for bacterial overgrowth. AIMS: The primary aims of this study were to: (1) characterize the relationship of prolonged small bowel transit time (SBTT) in patients undergoing WMC with SIBO as based on a positive lactulose breath testing (LBT); and (2) to assess the relationship of prolonged gastric, colonic, and whole gut transit times (WGTT) and additional motility parameters with SIBO (positive LBT). We also sought to evaluate the relationship of small bowel motility parameters (SB motility index, contractions per minute, and SB peak amplitudes) with LBT results. METHODS: We performed a retrospective study of consecutive patients who were referred for wireless motility testing at a single, tertiary care institution from April 2009 to December 2012. Of the 72 total patients identified, 34 underwent both WMC and LBT. Gastric, small bowel, colonic, WGTT, and SB motility parameters were measured and correlated with LBT results. Statistical methods utilized for data analysis include ANOVA, 2-sample t tests, nonparametric Kruskal Wallis test, Wilcoxon rank-sum test, and the Fisher exact test. RESULTS: Of the 37 patients who underwent both WMC and LBT, 24 (65%) were LBT positive. The mean SBTT among those who were LBT positive was 6.6 hours as compared with 4.2 hours in those who were LBT negative (P=0.04). Among patients who were LBT positive, 47.6% had prolonged SBTT (≥6 h), whereas only 7.7% of those who were LBT negative had a delay in their SBTT (P=0.01). In addition, patients who were LBT positive were more likely to have prolongation of both colonic and WGTT versus those who were LBT negative (CTT: positive LBT=64.4 h vs. negative LBT=35.5 h, P=0.02; WGTT: positive LBT=70.5 h vs. negative LBT=44.1 h, P=0.02). However, there were no statistical differences observed between the groups for gastric emptying times or other small intestinal motility parameters (SB motility index, contractions per minute, and peak amplitudes) between the 2 groups. CONCLUSIONS: Patients with underlying SIBO have significant delays in SBTT as compared with those without. The association between prolonged SBTT and positive LBT may be useful in identifying those patients with SIBO diagnosed by LBT and potentially target therapeutic options for those refractory to standard therapy. Interestingly, patients with positive LBT did not necessarily have a generalized gastrointestinal motility (similar GETs among groups), suggesting that small bowel transit specifically predisposes to the development of SIBO. Future, prospective studies are needed to further characterize intestinal dysmotility and other contributing pathophysiological mechanisms in SIBO and to investigate the potential benefits of prokinetics in this challenging patient population.

Low ileocecal valve pressure is significantly associated with small intestinal bacterial overgrowth (SIBO).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a significant and increasingly recognized syndrome. While the development may be multifactorial, impairment of the ileocecal valve (ICV), small bowel motility, and gastric acid secretion have been hypothesized to be risk factors. ICV dysfunction remains largely unexplored using standard technology. The wireless motility capsule (WMC) that evaluates pressure, pH, and temperature throughout the GI tract provides the ability to assess these parameters. AIMS: The primary aims of this study were to assess the relationship of ICV pressures, small bowel transit time (SBTT) and intestinal pH with lactulose hydrogen breath testing (LBT) results in subjects with suspected SIBO. METHODS: We retrospectively studied consecutive patients referred to our institution for WMC and LBT from 2010-2012. Ileocecal junction pressures (IJP), as a surrogate for ICV pressures, were defined as the highest pressure over a 4-min window prior to the characteristic ileocecal pH drop. SBTT and pH were calculated and compared with LBT results. RESULTS: Twenty-three patients underwent both WMC and LBT, with positive results observed in 15 (65.2%). IJP were significantly higher in LBT(-) negative vs. LBT(+) (79.9 vs. 45.1, p < 0.01). SBTT was significantly longer in LBT(+) versus LBT(-) (5.82 vs. 3.81 h, p = 0.05). Among LBT(+) subjects, gastric pH was significantly higher versus LBT(-) subjects (2.76 vs. 1.63, p = 0.01). There was poor correlation between IJP and other parameters (SBTT, small bowel pH, and gastric pH). CONCLUSIONS: Low IJP is significantly associated with SIBO. While this is physiologically plausible, to our knowledge, this is the first study to make this connection. Prolonged SBTT and higher pH are also independently associated with SIBO. Our findings add value of the WMC test as a diagnostic tool in patients with functional gastrointestinal complaints and suggest re-focus of attention on the ileocecal valve as a prominent player in intestinal disorders.

Nurse observation during colonoscopy increases polyp detection: a randomized prospective study.

OBJECTIVES: To determine whether a second observer during colonoscopy increases adenoma detection. METHODS: Consecutive patients undergoing screening colonoscopy were prospectively randomized to routine colonoscopy or physician and nurse observation during withdrawal. RESULTS: Of 502 patients, 249 were randomized to routine colonoscopy, and 253 to physician plus nurse observation during withdrawal. A total of 592 polyps were detected, 40 identified by the endoscopy nurse only. With nurse observation, 1.32 polyps and 0.82 adenomas were found per colonoscopy, vs. 1.03 polyps and 0.64 adenomas in the routine group, demonstrating a 1.29-fold and a 1.28-fold increase in the average number of polyps and of adenomas detected, respectively. The overall adenoma detection rate (ADR) was 44.1%, with trends toward increased ADR and all-polyp detection rate with nurse observation. CONCLUSIONS: Nurse observation during colonoscopy resulted in an increase in the number of polyps and adenomas found per colonoscopy, along with a trend toward improved overall ADR and all-polyp detection rate.

The association between urinary and fecal incontinence and social isolation in older women.

OBJECTIVE: To describe the association between social isolation and urinary incontinence and fecal incontinence in older women. METHODS: We conducted a secondary database analysis of the National Social Life, Health and Aging Project for women aged 57 to 85 years old. Our primary outcome was self-report of often feeling isolated. We explored self-report of daily urinary incontinence and weekly fecal incontinence. Two logistic regression analyses were performed to assess the association between often feeling isolated and (1) daily urinary incontinence and (2) weekly fecal incontinence. RESULTS: A total of 1412 women were included in our analysis. Daily urinary incontinence was reported by 12.5% (177/1412) of community-dwelling older women. More women with daily urinary incontinence reported often feeling isolated (6.6%; 95% confidence interval [CI], 1.3-11.9 vs 2.6%; 95% CI, 1.7-3.5; P = .04) compared with women without daily urinary incontinence. Women with daily urinary incontinence had 3.0 (95% CI, 1.1-7.6) increased odds of often feeling isolated after adjusting for depressive symptoms, age, race, education, and overall health. Weekly fecal incontinence was reported by 2.9% (41/1412) of women. Weekly fecal incontinence and often feeling isolated were associated on univariable analysis (crude odds ratio, 4.6; 95% CI, 1.4-15.1). However, after adjusting for depressive symptoms, age, race, education, and overall health the association between weekly fecal incontinence and often feeling isolated was not significant (adjusted odds ratio, 0.65; 95% CI, 0.1-5.3; P = .65). CONCLUSION: After adjusting for confounders, daily urinary incontinence was significantly associated with often feeling isolated. Weekly fecal incontinence was not found to be associated with often feeling isolated on multivariable logistic regression.