Relationship of Age and Gender to Motility Test Results and Symptoms in Patients with Chronic Constipation.

BACKGROUND/AIMS: Patients with chronic constipation (CC) exhibit symptoms and functional abnormalities upon testing, but their relationship to age and gender is unclear. We assessed age- and gender-related differences in symptoms, colon transit time, and anorectal motility, sensation, and expulsion. PATIENTS AND METHODS: Retrospective, post hoc data analysis of patients with CC, who underwent Wireless Motility Capsule (WMC), High-Resolution Anorectal Manometry (HR-ARM), Balloon Expulsion Test (BET) and Rectal Sensory Testing (RST). Clinical assessment was made by questionnaires. Standard WMC criteria for colonic transit time (CTT) and the London classification was used for HR-ARM analyses, and regression plots between age, gender, CTT, HR-HRM, RST and BET were calculated. RESULTS: We studied 75 women and 91 men. Abdominal pain, infrequent defecation, incomplete evacuation, defecatory straining, and multiple motility and anorectal function abnormalities were common. Abdominal pain was least frequently, and straining was most frequently associated with a motility abnormality. For each symptom, the highest prevalence was associated with failed BET. There was a significant increase in CTT with age only in men (p = 0.0006). In men, for each year of age there was a CTT increase of 1.02 h. The prevalence of abdominal pain and incomplete evacuation for females was significantly higher than that for males (both P < 0.05). The prevalence of low anal squeeze pressure for females was significantly higher than that for males, and the prevalence of poor rectal sensation for males was significantly higher than that for females (both P < 0.05). A significant decrease in basal anal and squeeze pressures with age occurred in women (p < 0.0001); an increase in age of one year was associated with a decrease in anal base pressure of 1.2 mmHg. Abnormal CTT and HR-ARM tests were associated with increased symptom frequency, but not severity. CONCLUSIONS: There are significant age- and gender-related differences in symptoms, CTT, and HR-HRM parameters, rectal sensation, and expulsion, that may influence the multifaceted management of constipation.

The relationship between esophageal acidity and symptom frequency in symptomatic nonerosive gastroesophageal reflux disease.

The present paper examines the extent to which novel measures of esophageal acid exposure can elucidate possible relationships between symptom perception and esophageal acidity in subjects with nonerosive gastroesophageal reflux disease. Recordings of esophageal pH and symptom occurrence from 20 subjects with nonerosive gastroesophageal reflux disease were analyzed. Interval esophageal acid exposure was calculated in two different ways for the interval that preceded each symptom in each subject. Interval esophageal acidity was calculated as the time-weighted acid concentration for the interval. Interval esophageal acid exposure time was calculated as the percentage of the total recording time that esophageal pH was less than pH 4 for the interval. There was a negative relationship between the probability of a symptom and interval esophageal acid exposure indicating the paradoxical finding that the lower the value of esophageal acid exposure, the higher the probability of a symptom. The time courses of symptoms and cumulative esophageal acidity resolved this paradox by indicating that esophageal acid exposure oscillates between longer periods of low esophageal acid exposure with a high number of symptoms reflecting high esophageal acid sensitivity, and shorter periods of high esophageal acid exposure with fewer symptoms reflecting low esophageal acid sensitivity. Thus, the present analyses show how novel measures of acidity can identify and also resolve a previously unrecognized paradoxical relationship between esophageal acid exposure and symptom frequency in subjects with nonerosive gastroesophageal reflux disease.

Post-reflux swallow-induced peristaltic wave (PSPW): physiology, triggering factors and role in reflux clearance in healthy subjects.

BACKGROUND AND AIMS: The underlying physiology of post-reflux swallow-induced peristaltic wave (PSPW) is unclear. We aimed to: 1) calculate the probability of a random association between reflux and PSPW; 2) characterize factors that could underlie triggering of PSPW and 3) assess the chemical clearance effect of PSPW in healthy asymptomatic subjects. METHODS: A total of 251 impedance-pH tracings from healthy asymptomatic subjects were analysed. Twenty consecutive tracings from this pool with 20-40 reflux episodes/24 h and a PSPW index higher than 50% were separately analyzed to evaluate the probability of a random association between reflux and PSPW. The characteristics of reflux episodes followed by a PSPW were compared with those not associated with PSPW. RESULTS: A mean time interval of 29.3 s between a reflux episode and the first swallow captured 71% of total reflux episodes, and 67% of accompanying swallows were non-random. Compared to reflux without PSPW, reflux episodes with PSPW were more frequently acidic (P = 0.048), mixed with gas (P < 0.0001), of high proximal extent (P < 0.0001), while awake (P < 0.0001), and with shorter chemical clearance time (P = 0.040). High proximal extent, gas presence and occurring while awake were independent factors associated with PSPW (P < 0.0001). CONCLUSION: Using a time window between reflux and PSPW of around 30 s, the probability of a chance association is around 30%. Reflux episodes with high proximal extent, containing gas and occurring while awake are important factors associated with PSPW in healthy subjects. Reflux episodes with PSPW have a shorter chemical clearance time.

Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. TRIAL REGISTRATION NUMBER: NCT03326713; clinicaltrials.gov.

Persistent constipation and abdominal adverse events with newer treatments for constipation.

BACKGROUND: Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. METHODS: We searched the medical literature using MEDLINE and Cochrane central register of controlled trials. Randomised, placebo-controlled trials that examined the use of methylnaltrexone, naloxegol, lubiprostone, prucalopride or linaclotide in adults with OIC, CIC and IBS-C were eligible for inclusion. The primary efficacy measure was relief of constipation. Adverse event data for abdominal symptoms were also analysed. KEY RESULTS AND FINDINGS: 25 publications were included in our analyses. The proportion of constipated individuals with active treatment was significantly lower than the proportion with placebo; however, in 15 of these 20 trials analysed, a majority of patients remained constipated with active treatment. Analyses of adverse event data revealed that the percentage of participants who experienced abdominal pain, diarrhoea and flatulence with active treatment was higher than that with placebo in the majority of trials analysed. CONCLUSIONS: Newer pharmacological treatments for constipation are superior to placebo in relieving constipation, but many patients receiving active treatment may remain constipated. In addition, all 5 of the treatments studied are accompanied by no change or a possible increase in the prevalence of abdominal symptoms, such as abdominal pain, diarrhoea and flatulence.

Exploring the physiologic role of human gastroesophageal reflux by analyzing time-series data from 24-h gastric and esophageal pH recordings.

Our previous finding of a fractal pattern for gastric pH and esophageal pH plus the statistical association of sequential pH values for up to 2 h led to our hypothesis that the fractal pattern encodes information regarding gastric acidity and that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity by influencing gastric secretion of acid or bicarbonate. Under our hypothesis values of gastric pH should provide information regarding values of esophageal pH and vice versa. We used vector autoregression, a theory-free set of inter-related linear regressions used to measure relationships that can change over time, to analyze data from 24-h recordings of gastric pH and esophageal pH. We found that in pH records from normal subjects, as well as from subjects with gastroesophageal reflux disease alone and after treatment with a proton pump inhibitor, gastric pH values provided important information regarding subsequent values of esophageal pH and values of esophageal pH provided important information regarding subsequent values of gastric pH. The ability of gastric pH and esophageal pH to provide information regarding subsequent values of each other was reduced in subjects with gastroesophageal reflux disease compared to normal subjects. Our findings are consistent with the hypothesis that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity, and that this ability is impaired in subjects with gastroesophageal reflux disease.

Levels of fatigue and distress in senior prostate cancer survivors enrolled in a 12-week randomized controlled trial of Qigong.

PURPOSE: Fatigue is a commonly reported symptom by prostate cancer survivors and is associated with significant distress and declines in quality of life. Qigong is a mind-body activity that consists of both physical activity and meditative aspects. This 12-week randomized controlled trial examined the feasibility and efficacy of a Qigong intervention for improving older prostate cancer survivors' levels of fatigue and distress. METHODS: Forty older (median age = 72, range = 58-93), fatigued (cut-off value of ≥ 1 on the CTCAEv4.0, >20 on a fatigue grading scale), and sedentary (<150 min of moderate exercise/week) prostate cancer survivors were randomized to 12 weeks of Qigong or stretching classes. Primary outcomes were feasibility (i.e., retention and class attendance rates) and fatigue [Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)], and secondary outcome was distress [Brief Symptom Inventory-18 (BSI-18)]. RESULTS: Study retention rates did not significantly differ between study groups (Qigong = 80 %, stretching = 65 %, p = 0.48). The Qigong group had significantly higher class attendance than the stretching group (p = 0.04). The Qigong group had significantly greater improvements in the FACIT-Fatigue (p = 0.02) and distress (i.e., BSI-18 Somatization, Anxiety, & Global Severity Index, p's < 0.05), than the Stretching group. CONCLUSIONS: This 12-week Qigong intervention was feasible and potentially efficacious in improving senior prostate cancer survivors' levels of fatigue and distress levels. Future, larger definitive randomized controlled trials are needed to confirm these benefits in older prostate cancer survivors and in racially and ethnically diverse populations. IMPLICATIONS FOR CANCER SURVIVORS: Qigong may be an effective nonpharmacological intervention for the management of senior prostate cancer survivors' fatigue and distress.

Findings from a national needs assessment of American Indian/Alaska native child welfare programs.

The National Child Welfare Resource Center for Tribes, a member of the Children's Bureau Child Welfare Training and Technical Assistance Network, conducted a national needs assessment of tribal child welfare. This assessment explored current practices in tribal child welfare to identify unique systemic strengths and challenges. A culturally based, multi-method design yielded findings in five areas: tribal child welfare practice, foster care and adoption, the Indian Child Welfare Act, legal and judicial, and program operations.

Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors.

BACKGROUND: A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI), 50% had pathologic esophageal acid exposure. AIM: We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH < 4. METHODS: We calculated integrated acidity and time pH < 4 from the 49 recordings of 24-hour gastric and esophageal pH from the Stanford study as well as from another study of 57 GERD subjects, 26 of whom were treated for 8 days with 20 mg omeprazole or 20 mg rabeprazole in a 2-way crossover fashion. RESULTS: The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH < 4 than when measured as integrated acidity. This difference was entirely attributable to a difference between the two measures during the nocturnal period. Nocturnal gastric acid breakthrough was not a useful predictor of pathologic nocturnal esophageal reflux. CONCLUSION: In GERD subjects treated with a PPI, measuring time esophageal pH < 4 will significantly overestimate the prevalence of pathologic esophageal acid exposure over 24 hours and during the nocturnal period.

Physician use of electronic medical records: issues and successes with direct data entry and physician productivity.

At Intermountain Health Care, we evaluated whether physicians in an ambulatory setting will voluntarily choose to enter data directly into an electronic health record (EHR). In this paper we describe the benefits of an EHR, as they exist in the current IHC application and the ways in which we have sought to minimize obstacles to physician data entry. Currently, of 472 IHC employed physicians, 321 (68%) routinely enter some data directly into the EHR without coercion. Twenty-five percent (80/321) of the physicians use voice recognition for some data entry. Twelve of our 95 ambulatory clinics have voluntarily adopted measures to eliminate paper charts. Of the 212 physicians who entered data in 2004, sixty-nine physicians (22%) increased their level of data entry, while 12 (6%) decreased. We conclude that physicians will voluntarily adopt an EHR system, and will continue and even increase use after implementation barriers are addressed.

Control of nocturnal gastric acidity: a role for low dose bedtime ranitidine to supplement daily omeprazole.

In some patients, proton pump inhibitors do not abolish nocturnal gastric acidity and additional evening antisecretory medication may be required. In 16 subjects with chronic heartburn, 24-hr gastric and esophageal pH were measured at baseline and again after six days of 20 mg omeprazole alone at 08:00 hr followed by placebo, 75 mg ranitidine, or 20 mg omeprazole at 22:00 hr. Integrated acidity was calculated from the cumulative, time-weighted mean acid concentrations (derived from pH values for each second). Baseline integrated gastric acidity increased progressively over 24 hr, whereas integrated esophageal acidity increased only until 22:00 hr. Morning omeprazole nearly abolished 24-hr esophageal acidity and significantly decreased overall gastric acidity but did not abolish nocturnal gastric acidity. Adding evening ranitidine or omeprazole nearly eliminated the nocturnal increase in gastric acidity. Integrated acidity was more sensitive than time pH < 4 in assessing gastric and esophageal acidity as well as their inhibition by omeprazole and ranitidine. In conclusion, integrated acidity provides novel information regarding the synergy of omeprazole plus ranitidine. Adding low-dose ranitidine helps control nocturnal gastric acidity that can occur with conventional omeprazole administration. Although the heartburn patients in the present study had nocturnal gastric acidity without accompanying nocturnal esophageal acid reflux, other patients who do have nocturnal esophageal reflux might profit from addition of bedtime ranitidine or another gastric antisecretory agent.

Measurement of meal-stimulated gastric acid secretion by in vivo gastric autotitration.

Measurement of meal- stimulated gastric acid secretion using manual intragastric titration is demanding in terms of personnel and specialized equipment. In the present study, we used a new method, in vivo gastric autotitration, to determine meal-stimulated gastric acid secretion. Gastric pH was measured every 4 s before, during, and after ingestion of a standard meal in 24 healthy subjects. Placebo, ranitidine (150 mg), ranitidine (75 mg), or famotidine (10 mg) was given 1 h after the beginning of the meal. Meal-stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro (119 mmol) and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Values for pH were also converted to acid concentration (mM), and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every fourth second of the postprandial recording period. Control meal-stimulated gastric acid secretion was 60 (40-71) mmol/h (median; interquartile range), and each histamine H(2)-receptor antagonist significantly decreased secretion by approximately 50%. Meal-stimulated acid secretion correlated directly with postprandial integrated gastric acidity (r = 0.72; P = 0.0001). Thus intragastric autotitration is a convenient, reproducible method for measuring gastric acid secretion after ingestion of a solid meal and offers several advantages over manual intragastric titration.