Mean Gastrointestinal Research Articles

Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms

No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. ClinicalTrials.gov Identifier: NCT03274687.

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial

PurposeTo assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. Material and methodsPatients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. ResultsAmong the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. ConclusionsIn this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

Gastrointestinal Tolerance of Formula-Fed Infants During the Immediate Postnatal Period in Saudi Arabia: An Observational Study.

Objective. Feeding intolerance during the early postnatal period can be distressing for families. To assess this, infants (n = 150) of mothers who had previously decided to exclusively or partially formula feed were enrolled ≤24 hours after birth. Methods. Infants were fed with a single ready-to-feed, 100% partially hydrolyzed whey protein-based formula until discharge, in accordance with standard hospital practice. Parents recorded daily the presence/severity of gastrointestinal (GI) symptoms/behaviors, rated from 0 (never) to 5 (always). A validated questionnaire was completed at discharge to evaluate symptoms of GI discomfort; scores can range from 0 to ~140 (lower scores indicate fewer symptoms). Results. Mean ± SD daily scores ranged from 0.12 ± 0.40 (fussiness/irritability) to 1.26 ± 0.90 (spitting up), indicating that GI symptoms/behaviors occurred, on average, "never" or "almost never." Mean GI discomfort scores were also very low (9.9 ± 7.4). Conclusion. These results indicate that the ready-to-feed formula was very well accepted and well tolerated during this period among healthy newborns in Saudi Arabia.

The Chemo-Gut Study: A Cross-Sectional Survey Exploring Physical, Mental, and Gastrointestinal Health Outcomes in Cancer Survivors.

Cancer treatments, such as chemotherapy, may adversely affect gastrointestinal (GI), physical and mental health in survivors of cancer. This study investigated associations between GI, mental and physical health outcomes, and cancer treatment-related variables, such as chemotherapy, in adult cancer survivors. A one-time cross-sectional survey with patient-reported outcomes was used. Cancer survivors (N = 317) aged ≥18years, living in Canada, who completed cancer treatments were included. Descriptive statistics, correlation, and linear regression analyses are reported. Mean age at diagnosis was 40.90 ± 15.40years. Most survivors received chemotherapy (86.1%). Persistent GI symptoms include constipation (53.6%), diarrhea (50.5%), and bloating/pain (54.9%). Mean GI symptom duration was 30.53 ± 33.42 months. Severity of GI symptom interference was moderate to extreme for 51.9% of survivors. Compared to normative values of 50 in healthy people, survivors scored poorer for mental health (M = 42.72 ± 8.16) and physical health (M = 45.55 ± 7.93), and reported more belly pain (M = 56.10 ± 8.58), constipation (M = 54.38 ± 6.81), diarrhea (M = 55.69 ± 6.77), and gas/bloating (M = 56.08 ± 8.12). Greater GI symptom severity was associated with poorer mental and physical health (P < .01). Chemotherapy was associated with increased belly pain (B = 4.83, SE = 1.65, P < .01) and gas/bloating (B = 3.06, SE = 1.45, P = .04). We provide novel evidence that many cancer survivors experience chronic, moderate to severe GI symptoms lasting for years after cancer treatment, which are associated with worse mental and physical health. Chemotherapy is associated with specific GI symptoms. Integrative therapies are needed to address GI symptoms in cancer survivors.

Measurement of intraluminal pH changes in the gastrointestinal tract of mice with gastrointestinal diseases

As a fundamental and essential property, gastrointestinal (GI) tract pH reflects its condition and changes in several GI diseases such as inflammatory bowel disease (IBD), gastritis, etc. As a result, accurately measuring the GI pH is crucial for treatment, diagnosis, and prevention of GI diseases and contributes to developing GI disease models for basic studies.However, among pH measuring studies with animal models, there is no reliable method that can reflect the value and changing trends of GI pH in actual patients. In the current study, we developed a fast, simple method with pH indicator paper to measure the GI pH changes with GI content in normal mice and mice with colitis or hepatitis.Results demonstrated that normal mice's mean GI pH values were between 6.0 and 8.0, which was consistent with previous reports. Furthermore, the GI pH of colitis and hepatitis model mice showed the same pattern of lower values in the intestine and higher values in the stomach compared with normal mice.Our simple and timesaving method can accurately measure the dramatic changes in the GI pH of mice with GI diseases and is suitable for measuring the pH of sticky liquids with limited volume. Given all the merits listed above, this method is helpful for further research.

Primary Endpoint Analysis of a Randomized Phase III Trial of Hypofractionated vs. Conventional Post-Prostatectomy Radiotherapy: NRG Oncology GU003

<h3>Purpose/Objective(s)</h3> To determine if hypofractionated post-operative prostate bed radiotherapy (HYPORT) does not increase patient-reported genitourinary (GU) or gastrointestinal (GI) toxicity over conventionally fractionated post-operative radiotherapy (COPORT). <h3>Materials/Methods</h3> Eligibility criteria were: 1) an undetectable PSA (< 0.1 ng/mL) with either margin negative pT3pN0/X or margin positive pT2pN0/X adenocarcinoma of the prostate or 2) a detectable PSA (≥ 0.1 ng/mL) and pT2/3pN0/X disease. HYPORT was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT was 66.6 Gy in 37 fractions of 1.8 Gy. Lymph node RT was not allowed. Androgen deprivation therapy (ADT) ≤ 6 months was allowed. Patients were stratified according to baseline Expanded Prostate cancer Index Composite (EPIC) score (four tiers based on GU and GI scores) and ADT use (yes vs. no) then randomized 1:1. The co-primary endpoints were based on change scores (24-month score minus baseline score) from the GU and GI domains of the EPIC. The hypothesis is that the mean change scores at 24 months are no worse for HYPORT than it is for COPORT. The non-inferiority margins were based on 0.5*standard error from NRG Oncology/RTOG 0415: -5 for GU and -6 for GI. Two hundred eighty-two patients provide ≥ 90% power with a one-sided alpha = 0.025 for each domain while inflating for non-compliance/loss to follow-up. <h3>Results</h3> Between July 2017 and July 2018, 298 patients were screened and 296 were randomized: 144 to HYPORT and 152 to COPORT. Compliance with the EPIC was 100% at baseline, 83% at the end of RT, 77% at 6 months, 78% at 12 months, and 73% at 24 months. At the end of RT, the HYPORT and COPORT mean GU change scores were neither clinically significant nor significantly different and remained so at 6 and 12 months. The mean GI change scores for HYPORT and COPORT were both clinically significant and significantly different at the end of RT (HYPORT mean GI = -15.0 vs COPORT mean GI = -6.8 <i>P</i> ≤ 0.01). However, both the HYPORT and COPORT mean GI change scores clinically and statistically significant differences were resolved at 6 and 12 months. The 24-month mean GU and GI change scores for HYPORT and COPORT remained neither clinically nor statistically significant (HYPORT mean GU = -5.2 vs COPORT mean GU = -3.0, <i>P</i> = 0.81; HYPORT mean GI = -2.2 vs COPORT mean GI = -1.5, <i>P</i> = 0.12). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT versus COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount (2-yr actuarial, 12% vs 8%, <i>P</i> = 0.29) or local failure (2-yr actuarial, 0.7% vs 0.8%, <i>P</i> = 0.35). <h3>Conclusion</h3> HYPORT is non-inferior to COPORT in terms of late patient-reported GU or GI toxicity. More follow-up is needed to appropriately assess disease control endpoints. In some clinic scenarios, HYPORT may be considered an acceptable practice standard.

Extracellular buffer choice influences acid-base responses and gastrointestinal symptoms

ABSTRACT To compare the bicarbonate kinetics and gastrointestinal (GI) symptom responses between an equal dose of sodium bicarbonate and sodium citrate using delayed-release capsules. Thirteen active males (age 20.5 ± 2.1 y, height 1.8 ± 0.1 m and body mass [BM] 76.5 ± 9.6 kg) consumed either 0.3 g.kg−1 BM sodium bicarbonate, sodium citrate or a placebo, using a double-blind, randomized crossover design. Blood bicarbonate ion (HCO3 −) concentration, pH and GI symptoms were measured pre-consumption and every 10 min for 180 min post-consumption. Blood HCO3 − concentration (P < 0.001) and pH (P = 0.040) were significantly higher in the sodium bicarbonate condition compared with sodium citrate condition up to 3 h post-consumption. Peak blood HCO3 – concentration was significantly higher with the sodium bicarbonate compared with citrate (P < 0.001). Mean GI symptom scores were lower (P = 0.037) for sodium citrate (1.5 ± 1.8 AU) than bicarbonate (2.6 ± 3.1 AU), with considerable inter-individual variability. No GI symptoms were reported following consumption of the placebo. Both substances increase HCO3 − values significantly, with sodium bicarbonate causing significantly higher pH and HCO3 − values than the same dose of sodium citrate, but results in slightly more severe GI symptoms.

Haemoconcentration, not decreased blood temperature, increases blood viscosity during cold water immersion.

Prolonged cold-water immersion (CWI) has the potential to cause significant hypothermia and haemoconcentration; both of which have previously been shown to independently increase blood viscosity in vitro. The purpose of this study was to determine the effect of CWI on blood viscosity and examine the relative contribution of decreased blood temperature and haemoconcentration. Ten healthy volunteers were immersed to mid-sternum in 10°C water for 90 minutes. Gastrointestinal (GI) temperature, haematocrit (Hct), and blood viscosity were measured pre- and post-CWI. CWI caused mean (SD) GI temperature to decrease from 37.5 (0.3)°C to 36.2 (0.7)°C (P < 0.05). CWI also caused mean Hct to increase from 40.0 (3.5)% to 45.0 (2.9)% (P < 0.05). As a result of the haemoconcentration and decreased GI temperature during CWI the mean blood viscosity increased by 19% from 2.80 (0.28) mPa·s⁻¹ to 3.33 (0.42) mPa·s⁻¹ (P < 0.05). However, when the pre-CWI blood sample was measured at the post-CWI GI temperature (36.2°C) there was no significant difference in the blood viscosity when compared to the pre-CWI (37.5°C) blood sample (2.82 (0.20) mPa·s-1 and 2.80 (0.28) mPa·s-1 respectively). Furthermore, the changes in Hct and blood viscosity during CWI were significantly correlated with an r = 0.84. The results of the current study show that prolonged, severe CWI causes a significant 19% increase in blood viscosity. In addition, the results strongly suggest that almost all of the increased blood viscosity seen following CWI is the result of haemoconcentration, not decreased blood temperature.

Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial.

We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption of R-lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single-center, double-blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600mg of R-LA or 1200mg of a 1:1 racemic R,S-LA mixture in single daily doses for 7 to 10 days, underwent a washout of at least 7 days, and then took the other form of LA for 7 to 10 days. At the end of each period on LA, GI symptoms were assessed with GI questions from the Monitoring of Side Effects Scale. Serum LA concentrations were measured before and 60, 90, 120, 180, and 240 minutes after the first and last day's dose of each form of LA to derive an area under the plasma concentration-time curve (AUC) and maximum serum concentration (Cmax ). Twenty participants enrolled (12 women; 15 secondary progressive MS, 5 primary progressive MS; mean age, 59.6 years). Two withdrew early due to symptoms while taking R,S-LA, and one withdrew early while taking R-LA. The mean GI Monitoring of Side Effects Scale score was 1.7 points lower on R-LA than on R,S-LA (P = .069), and there were fewer reports of each GI side effect when taking the R-LA than the R,S-LA (31 vs 60; P = .025). The AUC and Cmax for R-LA were bioequivalent for the 2 formulations (90% confidence intervals 97.4% to 99.3% for AUC and 93.4% to 98.2% for Cmax ). This study supports that in people with progressive MS, there is better GI tolerability and bioequivalent serum absorption of R-LA when 600mg of R-LA is taken as R-LA alone than when taken in a 1:1 racemic R,S-LA mixture.

The effect of fasting on gastrointestinal motility in healthy dogs as assessed by sonography.

To evaluate the effect of fasting on gastrointestinal (GI) motility in healthy dogs, as detected by 2D ultrasound. Prospective observational study. University Distributed Veterinary Learning Community. Ten healthy client-owned dogs. Dogs were fasted 24 hours following regular feeding. After this first feeding and during the 24 hour fasting period, 2D ultrasound was performed to detect sonographically visible GI contractions of the stomach, duodenum, and jejunum/ileum at T = 30 minutes, 6 hours, 12 hours, and 24 hours. Dogs were then fed a second meal after the 24-hour fast and ultrasound was repeated 30 minutes later (T = 24.5 h). Each site was scanned twice at each time point. Each scan lasted 3 minutes. The results were averaged and then divided by 3 to determine contractions per minute. One-way repeated measures ANOVA with post hoc Tukey's comparison test was used to detect statistical differences over time for each site examined. The mean GI contraction rates in the stomach, duodenum, and jejunum/ileum at T12 and T24 were significantly lower than the GI contraction rates at T30, T3, T6, and T24.5 (P < 0.05). The mean GI contraction rates in the stomach, duodenum, and jejunum/ileum at T30, T3, T6, and T24.5 were not statistically different from each other. Results of this study show that 2D sonography can be used to evaluate GI motility in dogs and that GI contraction rate decreases significantly in the stomach, duodenum, and jejunum/ileum after 12-24 hours of fasting.

O-174 The Combination Of Scgos/lcfos With Fermented Infant Formula Reduces The Incidence Of Colic In 4 Week Old Infants

Background and aims The effects on gastrointestinal (GI) tolerance and prevalence of colics (secondary outcome parameters) of a novel infant formula (IF) were explored in a randomised, controlled, double-blind, multicenter intervention study on growth, safety and GI tolerance. The novel IF combined the fermented IF Lactofidus™(LF) with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS, ratio 9:1, 0.8 g/100 ml). Methods 432 healthy, term infants aged 0–28 days were randomised after parent’s autonomous decision to discontinue breastfeeding. IF with scGOS/lcFOS and 50%LF (LF50+), IF with scGOS/lcFOS and 15%LF (LF15+), and as controls IF with 50%LF (LF50), or IF with scGOS/lcFOS (IF+) were tested. Parents completed standardised 7-day diaries with daily entries on GI symptoms and crying in monthly intervals until 17 weeks of age. Colic was defined by adapted Rome III criteria. Results Growth and safety outcomes were within the normal ranges. Based on low mean GI symptom-scores, the newly-developed IFs were well tolerated. The incidence of colic was highest (16.1%) at the 4 week visit and in line with literature (i.e. 20.5% at 4 weeks of age [Iacono et al., 2005]). The incidence of colic was significantly lower with LF50+ (8%) compared to IF+ (20%)(p = 0.034; chi-square test), and LF50 (20%)(p = 0.036) at the 4 week visit. Colic was found to be associated with clinically relevant flatulence, abdominal distension, constipation, diarrhoea, and regurgitation at four weeks of age. Conclusions The combination of scGOS/lcFOS with 50% fermented IF displayed a 60% lower incidence of colic in infants at 4 weeks of age compared to control IFs.

Consuming foods with added oligofructose improves stool frequency: a randomised trial in healthy young adults.

The impact of oligofructose (OF) intake on stool frequency has not been clearly substantiated, while significant gastrointestinal (GI) symptoms have been reported in some individuals. The aim of the present study was to determine the effects of OF on stool frequency and GI symptoms in healthy adults. In an 8-week, randomised, double-blind, parallel-arm study, ninety-eight participants were provided with 16g OF in yogurt and snack bars (twenty male and thirty female) or matching control foods (seventeen male and thirty-one female), to incorporate, by replacement, into their usual diets. Participants completed a daily online questionnaire recording stool frequency and rating four symptoms: bloating, flatulence, abdominal cramping and noise, each on a Likert scale from '0' for none (no symptoms) to '6' for very severe, with a maximum symptom intensity score of 24 (sum of severities from all four symptoms). Online 24h dietary recalls were completed during pre-baseline and weeks 4, 6 and 8 to determine fibre intake. When provided with OF foods, fibre intake increased to 24·3 (sem 0·5) g/d from pre-baseline (12·1 (sem 0·5) g/d; P<0·001). Stool frequency increased with OF from 1·3 (sem 0·2) to 1·8 (sem 0·2) stools per d in males and 1·0 (sem 0·1) to 1·4 (sem 0·1) stools per d in females during intervention weeks compared with pre-baseline (P<0·05),but did not change for control participants (males: 1·6 (sem 0·2) to 1·8 (sem 0·2); females: 1·3 (sem 0·1) to 1·4 (sem 0·1)). Flatulence was the most commonly reported symptom. Mean GI symptom intensity score was higher for the OF group (3·2 (sem 0·3)) v. control (1·7 (sem 0·1)) (P<0·01), with few participants reporting above moderate symptoms. No change in symptom intensity occurred over time. Consuming yogurt and snack bars with 16g OF improves regularity in young healthy adults. However, GI symptoms, resulting from an increase in oligofructose intake, may not diminish with time.

Obesity and gastrointestinal quality of life: A hospital-based survey

Objective: We tried to find whether obesity worsens gastrointestinal (GI) quality of life score among patients with GI symptoms. Materials and Methods: This descriptive study was performed in general surgery outpatient clinic in a slum part of a city. Body mass index (BMI) of the patients was measured. The patients with GI symptoms were included. The demographic data obtained. GI quality of life score questionnaires were performed. Results : The prevalence of being overweight and obesity were 32.4% and 40.1% respectively. There 442 patients with GI symptoms among 1250 outpatient admissions. The mean age, BMI and GI quality of life index scores of the patients were 46.3 (18-87), 31.1 (18.8-44.4) and 89.9 (63-121) respectively. The percentage of obese and overweight patients was significantly higher than the percentage of patients with normal weight. The quality of life decreased significantly in overweight and obese patients when compared with normal weight patients. Conclusion : The prevalence of obesity among females and older age was higher. Obesity is worsening the GI quality of life.

Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment

Data from two open-label trials (PRIOR and CURRENT) of women with postmenopausal osteoporosis or osteopenia were evaluated to assess whether monthly oral and quarterly intravenous (IV) ibandronate dosing improved self-reported gastrointestinal (GI) tolerability for patients who had previously experienced GI irritation with bisphosphonate (BP) use. In PRIOR, women who had discontinued daily or weekly BP treatment due to GI intolerance received monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women receiving weekly BP treatment who switched to monthly oral ibandronate for six months. GI symptom severity and frequency were assessed using the Osteoporosis Patient Satisfaction Questionnaire. In PRIOR, mean GI tolerability scores increased significantly at month 1 from screening for both treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001 for both). Most patients reported improvement in GI symptom severity and frequency from baseline at all post-screening assessments (>90% at Month 10). In the CURRENT subanalysis >60% of patients reported improvements in heartburn or acid reflux and >70% indicated improvement in other stomach upset at month 6. Postmenopausal women with GI irritability with daily or weekly BPs experienced improvement in symptoms with extended dosing monthly or quarterly ibandronate compared with baseline.

Gastrointestinal recovery after laparoscopic colectomy: results of a prospective, observational, multicenter study

Although evidence suggests that laparoscopic colectomy (LC) results in faster gastrointestinal (GI) recovery than open bowel resection, previous studies were performed at single institutions or generally not controlled for diet introduction or perioperative care, making the results difficult to interpret. A prospective, observational, multicenter study was planned to investigate GI recovery, length of hospital stay (LOS), and postoperative ileus (POI)-related morbidity after LC. Patients scheduled to undergo LC or hand-assisted laparoscopic (HAL) bowel resection and to receive opioid-based postoperative intravenous patient-controlled analgesia were enrolled in 16 U.S. centers. The study design was similar to that for trials of alvimopan phase 3 open laparotomy bowel resection using a standardized accelerated postoperative care pathway. The primary end points were time to upper and lower GI recovery (GI-2: toleration of solid food and bowel movement) and postoperative LOS. The secondary end points included POI-related morbidity (postoperative nasogastric tube insertion or investigator-assessed POI resulting in prolonged hospital stay or readmission), conversion rate, and protocol-defined prolonged POI (GI-2 > 5 postoperative days). In this study, 148 patients received hemicolectomy by the LC (42 left and 67 right) or HAL (39 left) approach. The conversion rate was 18.8% (25.4% LC left, 17.3% HAL left, 15% LC right). The mean time to GI-2 recovery was 4.4 days, and the mean postoperative LOS was 4.9 days, neither of which varied substantially by surgical approach. Prolonged POI occurred for 15 patients (10.1%), and POI-related morbidity occurred for 17 patients (11.5%). No patients were readmitted because of POI, whereas 3 patients (2%) were readmitted for all other causes. Mean GI recovery and LOS after LC were accelerated compared with those for patients in open laparotomy bowel resection clinical trials or those reported in large hospital databases (0.7 and 1.7-2.2 days, respectively). Overall POI-related morbidity was similar between the open bowel resection and LC populations, demonstrating that POI continues to present with important morbidity regardless of the surgical approach.

Adherence to and Gastrointestinal Tolerability of Monthly Oral or Quarterly Intravenous Ibandronate Therapy in Women with Previous Intolerance to Oral Bisphosphonates: A 12-Month, Open-Label, Prospective Evaluation

Background: Gastrointestinal (GI) symptoms and high dosing frequency have been cited as reasons for inadequate adherence to daily or weekly oral bisphosphonate therapy. Inadequate adherence may lead to poor therapeutic outcomes. Objective: The PRIOR study evaluated adherence to and GI tolerability of monthly therapy with oral and quarterly intravenous ibandronate in postmenopausal women with osteoporosis or osteopenia. Methods: This 12-month, multicenter, prospective, nonrandomized, open-label, noninferiority study included postmenopausal women with osteoporosis or osteopenia who had discontinued previous daily or weekly oral bisphosphonate therapy because of GI intolerance. Participants chose to receive either monthly oral ibandronate 150 mg or quarterly intravenous ibandronate 3 mg and were permitted to switch formulations once during the study. For oral treatment, adherence was assessed based on doses taken, as recorded on the case-report form; for intravenous treatment, adherence was assessed based on doses administered, as recorded by study site personnel. Participants who took ≥75% of protocol-specified doses were considered adherent. The rate of adherence to oral ibandronate was protocol defined as noninferior to that of intravenous ibandronate if the upper limit of the 2-sided 90% CI for the adjusted difference in adherence rates was >20%. At screening, participants assessed the tolerability of their previous bisphosphonate therapy using the GI Experience Survey; using the same instrument, they assessed the tolerability of ibandronate 1 month from baseline and at months 4, 7, and 10. Results: Of 543 participants in the intent-to-treat population, 147 (27.1%) chose to receive oral treatment and 396 (72.9%) chose to receive intravenous treatment. The mean age of participants was <66 years in both groups, and >90% of participants were white. A significantly greater proportion of participants who selected intravenous versus oral treatment had a primary diagnosis of osteoporosis (72.2% vs 57.1%, respectively; P < 0.001) and a history of fracture as an adult (35.6% vs 22.4%; P ≥ 0.004); significantly fewer recipients of intravenous versus oral ibandronate were currently working (29.0% vs 39.5%; P ≥ 0.021). Overall, 82.9% of participants had previously received alendronate and 44.9% had previously received risedronate. Eleven participants switched from oral to intravenous therapy and 16 switched from intravenous to oral therapy during the study. In the perprotocol population, 69.7% of participants in the oral group (101/145) and 82.9% of participants in the intravenous group (325/392) were adherent to their originally selected therapy. Adherence to oral therapy fell within the prespecified boundary for noninferiority to intravenous therapy (adjusted difference: 12.4%; 90% CI, 5.1–19.7). Mean GI tolerance scores were significantly improved from screening at all subsequent assessment times in both treatment groups ( P < 0.001); >75% of participants had a ≥10% increase in GI tolerability scores from screening. Both dosing regimens were generally well tolerated. Conclusion: Self-selected monthly oral or quarterly intravenous ibandronate therapy was associated with high adherence rates among these postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate treatment because of GI intolerance.

Evaluation of Risk Profiles for Gastrointestinal and Cardiovascular Adverse Effects in Nonselective NSAID and COX-2 Inhibitor Users

Newly approved drugs, in comparison with older drugs, are more often prescribed to patients who have not responded satisfactorily to established related drugs or as first-line therapy to patients with a high baseline risk for adverse outcomes (i.e. channelling). However, these patients are less likely to benefit from the prescribed drug and/or are more prone to adverse drug reactions. Therefore, it is difficult to unravel whether observed risks or increases in risk of new drugs are real, i.e. related to the pharmacology, or whether these are related to selective prescribing to patients who are more susceptible to adverse events because of some underlying risk factor(s). The channelling paradox may exist for cyclo-oxygenase (COX)-2 selective inhibitors ('coxibs') instead of traditional nonselective NSAIDs in relation to both gastrointestinal (GI) and cardiovascular (CV) safety. To evaluate the risk profiles for GI and CV adverse effects in nonselective NSAID and coxib new-user populations over time, in terms of a quantitative measure since the introduction of coxibs. This was a population-based cohort study using the Dutch pharmaceutical claims database (Foundation for Pharmaceutical Statistics). Eligible patients (>/=18 years) were those where the date of their first prescription (index date) of an NSAID (first-line [e.g. ibuprofen] or second-line [e.g. piroxicam] nonselective NSAID, COX-2 preferential NSAID or coxib) was between January 1999 and December 2003. For each patient, GI and CV risk profiles at index date were defined by a cumulative score derived from dispensing data (patient age, sex and history of medication use within 6 months of index date). Risk scores were categorized as low (score = 0), medium (1) or high (2+). Patients were recorded as switchers based on other NSAID use prior to the index date. Other information collected included the Chronic Disease Score (CDS). Crude odds ratios (ORs) were calculated for risk factors for each NSAID group versus first-line nonselective NSAID users as the reference cohort. The effect of calendar time was examined by plotting mean CV or GI risk score by quarter-year. Correlation between GI and CV scores was examined using the Pearson correlation coefficient (R). Data were stratified by patients' history of switching. The four cohorts comprised patients using: first-line nonselective NSAIDs (n = 42 750); second-line nonselective NSAIDs (n = 1771); COX-2 preferential NSAIDs (n = 3661) and coxibs (n = 4861) patients. New coxib users were most likely to have high GI and CV risk scores (OR 5.3 [95% CI 5.0, 5.6] and OR 2.2 [95% CI 2.1, 2.4], respectively). At the individual patient level, GI and CV risk profiles were moderately well correlated for all NSAID cohorts (R range 0.48 to 0.62). There was no remarkable change in mean GI or CV risk profile of patients over calendar time since the market introduction of coxibs. Of the four NSAID cohorts, new coxib users tended to have the highest numbers of GI and CV risk factors, with no obvious change over calendar time. There was also evidence of correlation between GI and CV risk scores. Thus, selective prescribing of coxibs applies to people with co-existing CV as well as GI risk factors. This is important when comparing the safety and/or efficacy of new therapies to existing therapies, and emphasizes the difficulties encountered by prescribers in assessing levels of risk when initiating coxib treatment.

Daily Stress and Gastrointestinal Symptoms in Women With Irritable Bowel Syndrome

Stress has been implicated as contributing to the initiation and exacerbation of bowel and discomfort symptoms in patients with irritable bowel syndrome (IBS). To examine the relationships of daily self-reported stress to gastrointestinal (GI) and psychological distress symptoms both across women and within woman in a comparison group of women without IBS and among subgroups of women with IBS. Women with IBS (n = 181; age = 18-49 years) who were divided into subgroups based on bowel pattern (constipation, n = 52; diarrhea, n = 67; alternating, n = 62) were compared to a group of women without IBS (n = 48). Self-report stress measures; abdominal (abdominal pain, bloating, and intestinal gas), bowel pattern (constipation, diarrhea), and intestinal gas; and psychological (anxiety and depression) distress symptoms were obtained daily over 1 month. Across-women and within-woman analyses were used. There were significant across-women correlations among mean daily stress, psychological distress, and GI symptoms in the total IBS group and the IBS bowel pattern subgroups. The across-women relationships between daily stress and GI symptoms were diminished when anxiety and depression were controlled in the analyses. Within-woman analyses showed little evidence of relationship between day-to-day variations in stress and day-to-day variations in GI symptoms; however, stress was strongly related to anxiety and depression. Gastrointestinal symptom distress is associated with self-reported stress in women with IBS. Psychological distress moderates the effects of stress on GI symptoms. The IBS treatment protocols that incorporate strategies that decrease stress and psychological distress are likely to reduce GI symptoms.

Enteric-Coated Mycophenolate Sodium can be Safely Administered in Maintenance Renal Transplant Patients: Results of a 1-Year Study

With the objective of enhancing upper gastrointestinal (GI) tolerability, enteric-coated mycophenolate sodium (EC-MPS, myfortic®, Novartis Pharma AG, Basel, Switzerland) has been developed. This double-blinded, 12-month study investigated whether renal transplant patients taking mycophenolate mofetil (MMF) can be safely converted to EC-MPS. Stable kidney transplant patients were randomized to receive EC-MPS (720 mg b.i.d.; n = 159) or continue receiving MMF (1000 mg b.i.d.; n = 163). The incidence of GI adverse events (AEs) was similar at 3 months (primary endpoint: EC-MPS 26.4%; MMF 20.9%; p = NS) and at 12 months (EC-MPS 29.6%; MMF 24.5%; p = NS). The increase from baseline in mean GI AE severity score, adjusted for duration, tended to be lower in EC-MPS patients (3 months: 0.15 vs. 0.20; 12 months: 0.23 vs. 0.47; p = NS). Neutropenia (<1500 cells/mm3) within the first 3 months (coprimary endpoint) was low in both groups (EC-MPS 0.6%; MMF 3.1%; p = NS). Although the overall incidence of infections was similar, the number of serious infections was significantly lower in EC-MPS patients (8.8% vs. 16.0%; p < 0.05). Similar rates of efficacy failure (EC-MPS 2.5%; MMF 6.1%; p = NS), biopsy-proven acute rejection (EC-MPS 1.3%; MMF 3.1%; p = NS) and biopsy-proven chronic rejection (EC-MPS 3.8%; MMF 4.9%; p = NS) were observed in both groups. In conclusion, renal maintenance patients can be converted from MMF to EC-MPS without compromising the safety and efficacy profile associated with MMF.

The relationship between daily life stress and gastrointestinal symptoms in women with irritable bowel syndrome.

Research on irritable bowel syndrome (IBS), a functional disorder of the gastrointestinal (GI) system, has linked GI symptoms to stress. This study examined the relationship between daily stress and GI symptoms across women and within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and controls (n = 26), controlling for menstrual cycle phase. Women (ages 20-45) completed daily health diaries for two cycles in which they monitored daily GI symptoms and stress levels. The Life Event Survey (LES) was used as a retrospective measure of self-reported stress. The across-women analyses showed higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to controls but no group differences in LES scores. The within-woman analyses found a significant and positive relationship between daily stress and daily symptoms in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no substantial impact on the results.