[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:The objectives of this study were to determine whether the symptoms of diarrhea (defined as loose or watery stools), constipation (hard or lumpy stools), abdominal pain, and bloating occur in episodes rather than sporadically in patients with irritable bowel syndrome (IBS); to identify rules for defining the onset and termination of symptom episodes; and to assess the overlap of these episodes.METHODS:IBS patients kept a symptom log in which they rated the consistency of each bowel movement (BM) on the Bristol Stool Scale for 3 months. Each night they transferred these data to an internet website and also rated abdominal pain and bloating for that day. Data were analyzed for 124 patients who completed at least 21 consecutive diary days (mean of 73 days) without taking laxative, antidiarrheal, or IBS-specific medications. For each symptom in each patient, we computed the correlation between consecutive observations (autocorrelations) in the diary to determine whether the symptom tended to occur in clusters of several instances, as would happen in episodes vs. happening randomly. Next, we compared different patterns by which diarrhea and nondiarrhea stools alternate to identify episode definitions that captured at least 75% of loose/watery stools. A similar pattern analysis was performed for constipation. Pain and bloating episodes were defined as days with an intensity rating >3 on a 0-10 scale. These patterns were converted into rules for defining the onset and termination of symptom episodes. Last, we used these episode definitions to examine the overlap of pain with episodes of diarrhea, constipation, and pain.RESULTS:Significant (P<0.05) autocorrelations were found in the Bristol Stool Scale ratings of 69.4% of patients and in the daily abdominal pain and bloating ratings of 52.4% and 68.5% of patients, respectively. Defining a diarrhea episode as two or more loose/watery stools never separated by >1 nonloose/watery stool or by a day without a BM captured 76% of all loose/water stools. Defining constipation episodes as two or more hard/lumpy stools never separated by >1 nonhard/lumpy stool captured 80% of hard/lumpy stools. Sequences of 3 or more days without a BM were also defined as constipation episodes because they were strongly associated with hard stools. Average episode durations were 2.1 days for diarrhea, 4.5 days for constipation, 3.1 days for pain, and 3.5 days for bloating. Overlap analysis showed that only 41.6% of constipation episode days and 67.0% of diarrhea episode days were pain episode days. Bloating and pain coexisted on 59.1% of days on which either type occurred.CONCLUSIONS:Loose/watery stools and hard/lumpy stools occur in well-defined episodes. Pain and bloating also occur in episodes, but contrary to the Rome criteria more than half of the pain episodes occur outside episodes of abnormal stool consistency.Am J Gastroenterol advance online publication, 1 July 2014; doi:10.1038/ajg.2014.181.
The American Journal of Gastroenterology 07/2014; · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
In a recent double-blinded clinical trial, the probiotic combination of Lactobacillus acidophilus NCFM (L-NCFM) and B-LBi07 reduced bloating symptoms in patients with functional bowel disorders; an effect more evident in those who reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic mu-opioid receptor (MOR) and cannabinoid receptor 2 (CB2) expression, and reduced visceral sensitivity.AimsTo determine if L-NCFM was the active component in the clinical trial and to investigate the mechanism of action in humans with mild to moderate abdominal pain.Methods
Caucasian women (n = 20) 18–70 years with mild to moderate abdominal pain were enrolled in a double-blind, two-armed, single-centre study. Patients were given either L-NCFM alone or in combination with B-LBi07 for 21 days at a total dose of 2×1010 CFU b.d. Colonic biopsies were collected during unsedated, unprepped flexible sigmoidoscopy before and at the end of probiotic consumption. mRNA and immunostaining were then performed on these biopsies. Patients kept symptom diaries for the 7 days prior to starting probiotic therapy and for the last 7 days of therapy.ResultsL-NCFM alone, but not with B-LBi07, induced colonic MOR mRNA and protein expression, as well as downstream signalling, as measured by enterocyte STAT3-phosphorylation. In contrast, CB2 expression was decreased. Both treatment groups trended towards improvement in symptoms, but the study was insufficiently powered to draw meaningful conclusions.Conclusions
Lactobacillus acidophilus NCFM modulates mu-opioid receptor expression and activity, while the combination of L-NCFM and B-LBi07 does not. This study provides a possible mechanism for action by which probiotics modulates pain sensation in humans (Clinical Trial Number: NCT01064661).
[Show abstract][Hide abstract] ABSTRACT: Summary
Ginger is one of the most commonly used herbal medicine for Irritable Bowel Syndrome (IBS) but no data exists about its effectiveness.
Double blind randomized controlled trial
University of North Carolina, Chapel Hill North Carolina, USA
Forty-five IBS patients were randomly assigned to three groups: placebo, one gram of ginger, and two grams of ginger daily for 28 days.
Main outcome measures
The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment.
There were 57.1% responders to placebo, 46.7% to one gram and 33.3% to two grams of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups.
This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn.
Complementary Therapies in Medicine 02/2014; · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fecal incontinence is a disabling symptom with medical and social implications, including fear, embarrassment, isolation and even depression. Most patients live in seclusion and have to plan their life around the symptom, with secondary impairment of their quality of life. Conservative management and biofeedback therapy are reported to benefit a good percentage of those affected. However, surgery must be considered in the non-responder population. Recently, sacral nerve electrostimulation, lately named neuromodulation, has been reported to benefit patients with fecal incontinence in randomized controlled trials more than placebo stimulation and conservative management, by some unknown mechanism. Neuromodulation is a minimally invasive procedure with a low rate of adverse events and apparently favorable cost-efficacy profile. This review is intended to expand knowledge about this effective intervention among the non-surgically skilled community who deals with this disabled group of patients.
World Journal of Gastroenterology 11/2013; 19(41):7048-7054. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychotherapy is not routinely recommended for in ulcerative colitis (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the gastrointestinal tract and may operate through immune-mediated pathways in chronic diseases.
To determine the feasibility and acceptability of HYP and estimate the impact of HYP on clinical remission status over a 1-year period in patients with an historical flare rate of 1.3 times per year.
A total of 54 patients were randomised at a single site to seven sessions of gut-directed HYP (n = 26) or attention control (CON; n = 29) and followed for 1 year. The primary outcome was the proportion of participants in each condition that had remained clinically asymptomatic (clinical remission) through 52 weeks post treatment.
One-way analysis of variance comparing HYP and CON subjects on number of days to clinical relapse favoured the HYP condition [F = 4.8 (1, 48), P = 0.03] by 78 days. Chi-squared analysis comparing the groups on proportion maintaining remission at 1 year was also significant [χ(2) (1) = 3.9, P = 0.04], with 68% of HYP and 40% of CON patients maintaining remission for 1 year. There were no significant differences between groups over time in quality of life, medication adherence, perceived stress or psychological factors.
This is the first prospective study that has demonstrated a significant effect of a psychological intervention on prolonging clinical remission in patients with quiescent ulcerative colitis (Clinical Trial # NCT00798642).
[Show abstract][Hide abstract] ABSTRACT: Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with anti-nociceptive and pro-nociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week pre-intervention phase, ambulatory patients with Chronic Daily Headache undergoing usual care were randomized to one of two intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in HUFA score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of sixty-seven patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs. -2.1; p<0.001) and the number of Headache Days per month (-8.8 vs. -4.0; p=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs. -1.2; p=0.01) and the n-6 in HUFA score (-21.0 vs. -4.0%; <0.001), and greater increases in anti-nociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs. +61.1%; p<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs. +27.2; p<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered anti-nociceptive lipid mediators, and improved quality-of-life in this population.
[Show abstract][Hide abstract] ABSTRACT: There is evidence that psychological factors affect the onset, severity and duration of irritable bowel syndrome (IBS). However, it is not clear which psychological factors are the most important and how they interact. The aims of the current study are to identify the most important psychological factors predicting IBS symptom severity and to investigate how these psychological variables are related to each other.
Study participants were 286 IBS patients who completed a battery of psychological questionnaires including neuroticism, abuse history, life events, anxiety, somatization and catastrophizing. IBS severity measured by the IBS Severity Scale was the dependent variable. Path analysis was performed to determine the associations among the psychological variables, and IBS severity.
Although the hypothesized model showed adequate fit, post hoc model modifications were performed to increase prediction. The final model was significant (Chi(2)=2.2; p=0.82; RMSEA<.05) predicting 36% of variance in IBS severity. Catastrophizing (standardized coefficient (β)=0.33; p<.001) and somatization (β=0.20; p<.001) were the only two psychological variables directly associated with IBS severity. Anxiety had an indirect effect on IBS symptoms through catastrophizing (β=0.80; p<.001); as well as somatization (β=0.37; p<.001). Anxiety, in turn, was predicted by neuroticism (β=0.66; p<.001) and stressful life events (β=0.31; p<.001).
While cause-and-effect cannot be determined from these cross-sectional data, the outcomes suggest that the most fruitful approach to curb negative effects of psychological factors on IBS is to reduce catastrophizing and somatization.
Journal of psychosomatic research 06/2013; 74(6):486-92. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:Epidemiological studies support an association of self-defined constipation with fiber and physical activity, but not liquid intake. The aims of this study were to assess the prevalence and associations of dietary fiber and liquid intake to constipation.METHODS:Analyses were based on data from 10,914 adults (≥20 years) from the 2005-2008 cycles of the National Health and Nutrition Examination Surveys. Constipation was defined as hard or lumpy stools (Bristol Stool Scale type 1 or 2) as the "usual or most common stool type." Dietary fiber and liquid intake from total moisture content were obtained from dietary recall. Co-variables included: age, race, education, poverty income ratio, body mass index, self-reported general health status, chronic illnesses, and physical activity. Prevalence estimates and prevalence odds ratios (POR) were analyzed in adjusted multivariable models using appropriate sampling weights.RESULTS:Overall, 9,373 (85.9%) adults (4,787 women and 4,586 men) had complete stool consistency and dietary data. Constipation rates were 10.2% (95% confidence interval (CI): 9.6, 10.9) for women and 4.0% (95% CI: 3.2, 5.0) for men (P<.001). After multivariable adjustment, low liquid consumption remained a predictor of constipation among women (POR: 1.3, 95% CI: 1.0, 1.6) and men (POR: 2.4, 95% CI: 1.5, 3.9); however, dietary fiber was not a predictor. Among women, African-American race/ethnicity (POR: 1.4, 95% CI: 1.0, 1.9), being obese (POR: 0.7, 95% CI: 0.5,0.9), and having a higher education level (POR: 0.8, 95% CI: 0.7, 0.9) were significantly associated with constipation.CONCLUSIONS:The findings support clinical recommendations to treat constipation with increased liquid, but not fiber or exercise.Am J Gastroenterol advance online publication, 9 April 2013; doi:10.1038/ajg.2013.73.
The American Journal of Gastroenterology 04/2013; · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to confirm that fecal urgency and diarrhea are independent risk factors for fecal incontinence (FI), to identify obstetrical risk factors associated with FI in women with irritable bowel syndrome, and to determine whether obstetric anal sphincter injuries interact with diarrhea or urgency to explain the occurrence of FI.
The study is a supplement to a diary study of bowel symptoms in 164 female patients with irritable bowel syndrome. Subjects completed daily bowel symptom diaries for 90 consecutive days and rated each bowel movement for stool consistency and presence of urgency, pain, and FI. All female participants from the parent study were invited to complete a telephone-administered 33-item bowel symptom and obstetric history questionnaire, which included the fecal incontinence severity index.
Of the 164 women in the parent study, 115 (70.1%) completed the interview. Seventy-four (45.1%) reported FI on their diary including 34 (29.6%) who reported at least 1 episode per month, 112 (97.4%) reported episodes of urgency, and 106 (92.2%) reported episodes of diarrhea. The mean fecal incontinence severity index score was 13.9 (9.7). On multivariable analysis, FI was significantly associated with parity (P = 0.007), operative abdominal delivery (P = 0.049), obstetrical sphincter lacerations (P = 0.007), fecal urgency (P = 0.005), diarrhea (P = 0.008), and hysterectomy (P = 0.004), but was not associated with episiotomy, pelvic organ prolapse, or urinary incontinence. The synergistic interactions of obstetric anal sphincter laceration with urgency (P = 0.002) and diarrhea (P = 0.004) were significant risk factors for FI.
Fecal urgency and diarrhea are independent risk factors for FI, and they interact with obstetric anal sphincter laceration to amplify the risk of FI.
Journal of Pelvic Medicine and Surgery 01/2013; 19(1):40-5.
[Show abstract][Hide abstract] ABSTRACT: To create and validate empirically derived questionnaires that measure non-gastrointestinal symptoms and disorders that co-exist with irritable bowel syndrome (IBS).
A systematic review of the world literature identified all non-GI symptoms and diagnoses known to have excess frequency in IBS patients. These data were used to create the Recent Physical Symptoms Questionnaire (RPSQ), which measures somatization (the psychological tendency to report multiple physical symptoms), and the Comorbid Medical Conditions Questionnaire (CMCQ). The psychometric properties of these questionnaires were assessed in two studies: 109 IBS patients in Study I; 286 IBS patients and 67 healthy controls in Study II.
In Study I, the RPSQ and CMCQ showed high test-retest reliability (r=.88 and .95) and good internal consistency (Cronbach alphas: .86 and .70, respectively). In Study II, principal components analysis demonstrated that the RPSQ is a homogeneous somatization scale, but the CMCQ could be divided into 4 subscales: one for psychiatric disorders and 3 for different types of somatic disorders. Concurrent validity of the RPSQ was shown by strong correlations with the Cornell Medical Index (CMI) and the Brief Symptom Inventory-18 (BSI-18) somatization scales. The validity of CMCQ responses was not assessed. Discriminant validity was modest: the BSI-18 anxiety and depression scales were less strongly correlated with the RPSQ than the BSI-18 somatization scale. The RPSQ and CMCQ scores of IBS patients were significantly higher than the scores of healthy controls (P<.001).
The RPSQ and CMCQ are psychometrically sound measures of somatization and medical comorbidities in IBS.
Journal of psychosomatic research 11/2012; 73(5):351-5. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The functional gastrointestinal disorders (FGIDs) often show inadequate response to usual medical care. Psychological treatments can help improve FGID patient outcomes, and such treatment should be considered for patients who have moderate or severe symptoms after 3 to 6 months of medical care, and those whose symptoms are clearly exacerbated by stress or emotional symptoms. Effective psychological treatments, based on multiple randomized controlled trials, include cognitive behavioral therapy (CBT) and hypnosis for irritable bowel syndrome and pediatric functional abdominal pain; CBT for functional chest pain; and biofeedback for dyssynergic constipation in adults. Successful referral by the gastroenterologist for psychological treatment is facilitated by educating the patient about the rationale for such treatment, reassurance about the diagnosis and continuation of medical care, firm doctor-patient therapeutic alliance, and identification of, and communication with, an appropriate psychological services provider.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2012; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Irritable bowel syndrome (IBS) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations. We hypothesized that mindfulness training (MT), which promotes nonreactive awareness of emotional and sensory experience, may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisals of gastrointestinal sensations. Seventy five female IBS patients were randomly assigned to participate in either 8 weeks of MT or a social support group. A theoretically grounded, multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life. Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisals of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference. Hence, MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS.
Journal of Behavioral Medicine 12/2011; 35(6). · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to determine how variable stool consistency is in patients with irritable bowel syndrome (IBS) and to assess the relationship between stool consistency and gastrointestinal symptoms.
Individuals with a physician diagnosis of IBS were recruited by advertisement. Enrollment questionnaires included the Rome III Diagnostic Questionnaire and IBS Symptom Severity Scale. Then, 185 patients meeting the Rome criteria for IBS rated the consistency (using the Bristol Stool Scale) of each bowel movement (BM) for 90 days and whether the BM was accompanied by pain, urgency, or soiling. Each night, they transferred BM ratings from a paper diary to an internet form and also reported the average daily intensity of abdominal pain, bloating, bowel habit dissatisfaction, and life interference of bowel symptoms. Only the longest sequence of consecutive days of diary data was used in the analysis (average of 73 days).
Patients were 89% females with average age 36.6 years. Among the patients, 78% had both loose/watery and hard/lumpy stools; the average was three fluctuations between these extremes per month. The proportion of loose/watery stools correlated r=0.78 between the first and second months and the proportion of hard/lumpy stools correlated r=0.85 between months. Loose/watery stools were associated with more BM-related pain, urgency, and soiling than hard/lumpy or normal stools; however, IBS-C patients had significantly more BM-unrelated abdominal pain, bloating, dissatisfaction with bowel habits, and life interference than IBS-D patients. Questionnaires overestimated the frequency of abnormal stool consistency and gastrointestinal symptoms compared with diaries.
Stool consistency varies greatly within individuals. However, stool patterns are stable within an individual from month to month. The paradoxical findings of greater symptom severity after individual loose/watery BMs vs. greater overall symptom severity in IBS-C implies different physiological mechanisms for symptoms in constipation compared with diarrhea. Daily symptom monitoring is more sensitive and reliable than a questionnaire.
The American Journal of Gastroenterology 11/2011; 107(2):286-95. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In clinical trials, lubiprostone reduced the severity of abdominal pain. The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time.
Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week cross-over study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 μg day(-1) of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries.
Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs 3.44, P < 0.001). However, thresholds for pain (17.36 vs 17.83 mmHg, lubiprostone vs placebo) and urgency to defecate (14.14 vs 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs 51.81 h), and neither pain sensitivity nor transit time was a significant predictor of clinical pain.
Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency.
Neurogastroenterology and Motility 10/2011; 23(10):944-e400. · 2.94 Impact Factor