Worldwide population prevalence and impact of sub-diagnostic gastrointestinal symptoms.

BACKGROUND: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms. AIMS: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs. METHODS: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions. RESULTS: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment. CONCLUSIONS: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice.

Preliminary development and validation of the Patient-Physician Relationship Scale for physicians for disorders of gut-brain interaction.

BACKGROUND: An effective patient-physician relationship (PPR) is essential to the care of patients with irritable bowel syndrome (IBS). After developing a PPR questionnaire for patients, we sought to develop and validate an IBS-specific instrument to measure physician expectations of the PPR. METHODS: We conducted focus groups about PPRs among 15 clinicians who treat patients with IBS from community and academic centers. Qualitative analysis was used to generate the Patient-Physician Relationship Scale -Physician RESULTS: The PPRS-Physician contained 35 questions pertaining to interpersonal and psychosocial features considered desirable or undesirable in a relationship with IBS patients. 1113 physicians (22%) completed the survey. Physicians were predominantly middle-aged (mean = 55.1 years), male (85.0%), white (74.5%), and practiced primarily within group settings (61.6%), with an average of 25.7% of their patients having IBS. Factor analysis revealed three relevant factors: interfering attributes, positive attributes, and personal connection. The scale ranged from possible 0 to 100 (mean = 83.8; SD = 8.38). Cronbach's alpha reliability measure of the scale was 0.938, indicating high internal consistency. There was a significant moderate, positive correlation between JSPE and the PPRS (P < 0.001, r = 0.488), establishing concurrent validity. CONCLUSIONS: We describe the development and validation of the first questionnaire to measure physician expectations of the PPR. This instrument can be used clinically, and for future studies on physician communication.

Can the Sum of Adenoma Diameters (Adenoma Bulk) on Index Examination Predict Risk of Metachronous Advanced Neoplasia?

BACKGROUND: Recent data suggest that adenoma size and number are more important predictors of metachronous colorectal neoplasia than advanced histology. Furthermore, there is poor reproducibility in diagnosing advanced histology; high-grade dysplasia and villous histology. Therefore we developed a new metric, adenoma bulk, the sum of diameters of all baseline adenomas, regardless of advanced features. GOAL: Compare the predictive value for metachronous advanced neoplasia of adenoma bulk to conventional paradigm. STUDY: Data were collected prospectively in a multicenter adenoma-chemoprevention trial (2004 to 2013). For the conventional paradigm, high-risk baseline findings were defined as ≥3 adenomas, large adenomas (≥1 cm) or adenomas with villous components or high-grade dysplasia. Adenoma bulk was examined across quartiles and as a continuous variable. Predictive characteristics (sensitivities, specificities, c-statistics) for metachronous advanced neoplasia using conventional criteria and adenoma bulk were calculated. receiver operator characteristic curves were computed using logistic regression. RESULTS: In total, 1948 adults had index and follow-up colonoscopies (mean follow-up, 45.2 mo). Those with an adenoma bulk ≥10 mm (4th quartile) had a higher metachronous advanced neoplasia risk (14.4% vs. 6.9-8.2% in lower 3 quartiles; P=0.0002). The c-statistics and sensitivities (specificity fixed at 0.73) for the adenoma bulk and conventional models were 0.587 and 0.563 (P=0.17) and 0.396 and 0.390, respectively. CONCLUSIONS: Categorizing sporadic adenoma patients as high versus low risk for metachronous advanced neoplasia by adenoma bulk of

Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk.

In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF (Plinear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend (Plinear trend=0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants (Plinear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451-8. ©2017 AACR.

Developing and Evaluating a Clinic-Based Decision Aid Delivery System.

Background: Despite evidence of their benefits, decision aids (DAs) have not been widely adopted in clinical practice. Quality improvement methods could help embed DA delivery into primary care workflows and facilitate DA delivery and uptake, defined as reading or watching DA materials. Objectives: 1) Work with clinic staff and providers to develop and test multiple processes for DA delivery; 2) implement a systems approach to measuring delivery and uptake; 3) compare uptake and patient satisfaction across delivery models. Methods: We employed a microsystems approach to implement three DA delivery models into primary care processes and workflows: within existing disease management programs, by physician request, and by mail. We developed a database and tracking tools linked to our electronic health record and designed clinic-based processes to measure uptake and satisfaction. Results: A total of 1144 DAs were delivered. Depending on delivery method, 51% to 73% of patients returned to the clinic within 6 months. Nurses asked 67% to 75% of this group follow-up questions, and 65% to 79% recalled receiving the DA. Among them, uptake was 23% to 27%. Satisfaction among patients who recalled receiving the DA was high. Eighty-two to 93% of patients reported that they liked receiving this patient education information, and 82% to 91% reported that receiving patient education information like this is useful to them. Conclusion: Our results demonstrate the realities of clinical practice. One fourth to one third of patients did not return for a follow-up visit. Although nurses were able to assess uptake in the course of their usual duties, the results did not achieve the standards typically expected of clinical research. Despite these limitations, uptake, though modest, was similar across delivery methods, suggesting that there are multiple strategies for implementing DAs in clinical practice.

Smoking-associated risks of conventional adenomas and serrated polyps in the colorectum.

PURPOSE: Prior studies suggest cigarette smoking is associated with 1.5- to twofold increased risk of colorectal adenomas and possibly a higher risk of serrated polyps. Further clarification of risk differences between adenomas and serrated polyps is needed with regard to co-occurrence and polyp location. METHODS: We conducted a combined analysis of conventional adenoma and serrated polyp occurrence using individual-level data from 2,915 patients participating in three colonoscopy-based clinical trials. All participants had ≥1 adenomas removed at baseline and were followed for up to 4 years. Smoking habits and other lifestyle factors were collected at baseline using questionnaires. We used generalized linear regression to estimate risk ratios and 95 % confidence intervals. RESULTS: Smokers were at slightly increased risk of adenomas compared to never smokers [current: RR 1.29 (95 % CI 1.11-1.49) and former: RR 1.18 (1.05-1.32)]. Smoking was associated with greater risk of serrated polyps [current: RR 2.01 (1.66-2.44); former: RR 1.42 (1.20-1.68)], particularly in the left colorectum. Associations between current smoking and occurrence of serrated polyps only [RR 2.33 (1.76-3.07)] and both adenomas and serrated polyps [RR 2.27 (1.68-3.06)] were more pronounced than for adenomas only [RR 1.31 (1.08-1.58)]. Results were similar for other smoking variables and did not differ by gender or for advanced adenomas. CONCLUSIONS: Cigarette smoking has only a weak association with adenomas, but is associated with a significantly increased risk of serrated polyps, particularly in the left colorectum. Since a minority of left-sided serrated polyps is thought to have malignant potential, the role of smoking in initiation phases of carcinogenesis is uncertain.

Partner burden in irritable bowel syndrome.

BACKGROUND & AIMS: Studies have described the burden experienced by caregivers and next of kin to patients with diseases such as cancer. However, the burden of functional gastrointestinal disorders on partners of patients has not been determined. We aimed to quantify the degree of burden to partners of patients with irritable bowel syndrome (IBS), to describe the factors that affect the burden perceived, and to identify the areas of relationship that are affected. METHODS: We surveyed 152 patients diagnosed with IBS at a tertiary gastrointestinal clinic, on the basis of Rome III criteria, and their partners. Their partners completed questionnaires including the Zarit Burden Interview (ZBI), Relationship Satisfaction Scale, and questions on sexual relationships. Patients with IBS were rated for disease severity by using the Functional Bowel Disease Severity Index. We compared findings with those from 39 partners of healthy individuals (controls). RESULTS: There were no significant demographic differences between the partners of patients with IBS and controls; demographics had no effect on burden. Burden was significantly higher among partners of IBS patients (mean ZBI score, 22.1) than controls (mean ZBI score, 11.5) (P = .0002). The degree of burden was directly related to IBS severity (P < .0001). There were inverse relationships between partners' rating of burden (ZBI) and relationship quality (R = -0.60; P < .001) and sexual satisfaction (R = -0.56; P < .0001). There was no difference in the Relationship Satisfaction Scale scores (4.25 vs 4.19; P = .78) or sexual relationship (6.47 vs 6.21; P = .64) between partners of IBS patients and controls, respectively. CONCLUSIONS: Partners of patients with IBS have a significant burden (on the basis of ZBI score), compared with partners of healthy individuals. Perceived burden increases with IBS severity and poorer sexual and relationship satisfaction.

The digital rectal examination: a multicenter survey of physicians' and students' perceptions and practice patterns.

OBJECTIVES: The digital rectal examination (DRE) may be underutilized. We assessed the frequency of DREs among a variety of providers and explored factors affecting its performance and utilization. METHODS: A total of 652 faculty, fellows, medical residents, and final-year medical students completed a questionnaire about their use of DREs. RESULTS: On average, 41 DREs per year were performed. The yearly number of examinations was associated with years of experience and specialty type. Patient refusal rates were lowest among gastroenterology (GI) faculty and highest among primary-care doctors. Refusal rates were negatively correlated with comfort level of the physician in performing a DRE. More gastroenterologists used sophisticated methods to detect anorectal conditions, and gastroenterologists were more confident in diagnosing them. Confidence in making a diagnosis with a DRE was strongly associated with the number of DREs performed annually. CONCLUSIONS: The higher frequencies of performing a DRE, lower refusal rate, degree of comfort, diagnostic confidence, and training adequacy were directly related to level of experience with the examination. Training in DRE technique has diminished and may be lost. The DRE's role in medical school and advanced training curricula needs to be re-established.

Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome.

UNLABELLED: OBFECTIVES: Narcotic bowel syndrome (NBS) is characterized by a paradoxical increase in abdominal pain associated with continued or escalating dosages of narcotics. This study evaluated the clinical and psychosocial features of patients with NBS and the response to detoxification treatment. METHODS: For 2 years, 39 patients seen by the GI consult service at the University of North Carolina at Chapel Hill (UNC) with presumed NBS were placed on a detoxification program. Clinical, psychosocial, health status, and outcome data were obtained before and after detoxification. Our aims were to: (i) clinically characterize patients with presumed NBS, (ii) assess the clinical response and adverse effects to detoxification, (iii) identify clinical and psychosocial predictors of treatment response, and (iv) determine the clinical outcome at 3 months after detoxification and the time frame for patients who revert back to narcotics. RESULTS: Of the 39 patients detoxified, 89.7% met predefined criteria. Patients were mostly well educated (14.5 ± 2.3 years of school), female (92.3%), and with a variety of diagnoses (21% irritable bowel syndrome IBS/functional, 37% inflammatory bowel disease and other structural, 29% fibromyalgia and other functional somatic, or orthopedic, and 13% postoperative or other). They reported high health-care use (15.3 ± 10.1 MD visits/6 months; 6.5 ± 6.1 hospitalizations/2 years, 6.4 ± 2.0 surgeries/lifetime), and 82.1% were jobless. Despite high dosages of narcotics (total intravenous (IV) morphine equivalent 75.3 ± 78.0 mg/day), pain scores were rated severe (52.9 ± 28.8 visual analog scale (VAS); 257.1 ± 139.6 functional bowel disorder severity index (FBDSI); 17.2 ± 10.2 (McGill Pain and greater than labor or postoperative pain). Multiple symptoms were reported (n = 17.8 ± 9.2) and rated as moderate to severe. Psychosocial scores showed high catastrophizing (19.9 ± 8.6); poor daily function (Short Form-36 (SF-36) physical 28.3 ± 7.7, mental 34.3 ± 11.0; worse than tetraplegia); 28.2% were clinically depressed and 33.3% anxious (Hospital Anxiety and Depression Scale (HADS)). Detoxification was successfully completed by 89.7%; after detoxification, abdominal pain was reduced by 35% (P < 0.03) and nonabdominal pain by 42% (P < 0.01) on VAS, and catastrophizing significantly improved (P < 0.01). Responder status was met in 56.4% with 48.7% achieving a ≥ 30% reduction in pain. By 3 months after detoxification, 45.8% had returned to using narcotics. For those who remained off narcotics at 3 months, the VAS abdominal pain score was 75% lower than pretreatment when compared with those who went back on narcotics (24% lower). Successful detoxification and a good clinical response was associated with low abuse potential (Current Opioid Misuse Measure (COMM) score < 9). CONCLUSIONS: Despite severe pain, poor coping, and poor health status, almost all patients with NBS undergoing detoxification were able to stop using narcotics and have significant improvement in pain and coping. However, almost ½ reverted to narcotic use at 3 months. Those who stayed off narcotics showed greater improvement in pain scores. This study provides a rationale for treating patients with NBS by detoxification in order to improve their clinical status. Further work is needed to understand the reasons for the high recidivism rate.

Development and validation of the irritable bowel syndrome satisfaction with care scale.

BACKGROUND & AIMS: Satisfaction with care is an important measure of quality, from the patients' perspective, and could also affect outcomes. However, there is no standard measure of patient satisfaction for irritable bowel syndrome (IBS) care; a multi-item, condition-specific instrument is needed. METHODS: Using standard qualitative methods, we conducted focus groups to identify items that patients associated with satisfaction in their care for IBS. These and additional items identified by experts were placed into a preliminary questionnaire, which was refined through pilot testing and cognitive debriefing by additional patients, as well as standard statistical methods. The resulting instrument and several external validation measures were administered to 300 adult US patients with IBS. Factor analysis was performed to identify clinically relevant subscales and then psychometric properties were assessed. RESULTS: We developed an IBS satisfaction with care scale (IBS-SAT) that has 38 items from 5 clinically relevant subscales (connection with provider, education, benefits of visit, office attributes, and access to care). This IBS-SAT had a high level of internal consistency (Crohnbach's α = .96). Convergent validity was established by correlations between the IBS-SAT and a single, global satisfaction with care question (r = 0.68; P < .001), and a generic, multi-item satisfaction scale (physician satisfaction questionnaire-18) (r = 0.75, P < .001). Discriminant validity (among known groups) was established across groups that were stratified based on IBS-quality of life (r = 0.34; P < .0001), IBS severity (functional bowel disorders severity index) (r = -0.21; P < .001), and number of unmet expectations (r = -0.38; P < .0001). CONCLUSIONS: The IBS-SAT is a validated measure of patient satisfaction with IBS care. As a new, condition-specific instrument, it is likely to be a useful tool for quality measurement, health services research, and clinical trials.

Characterization of episodes of irritable bowel syndrome using ecological momentary assessment.

OBJECTIVES: Patients with irritable bowel syndrome (IBS) report that symptoms occur as episodes. The nature and frequency of episodes have not been well studied. METHODS: Using modified ecological momentary assessment (EMA), we examined clinical factors attributed to IBS symptom episodes and compared them with nonsymptom episode periods in patients with IBS-D (N=21), IBS-C (N=18), or IBS-M (N=19), and healthy controls (N=19). Symptoms were rated over 14 days on a visual ordinal scale (VOS: 0-10) randomly in morning, midday, and evening, and at wake up, bedtime, prebowel movement, and postbowel movement. Scores were evaluated for total group and across subgroups and between EMA and daily diary cards on the same day. RESULTS: Subjects (n=57/59) reported symptom episodes 34% of the time. Episodes showed significantly higher pain levels (3.6 vs. 1.64, P<0.0001), bloating (4.57 vs. 3.02, P<0.0001), stress (3.54 vs. 2.59, P<0.0001), and decreased well-being (5.29 vs. 6.16, P<0.0001). Episode frequency/2 weeks was greatest for IBS-D (10.7±7.05) than IBS-C (8.4±5.76) and IBS-M (7.1±4.45) (P=nonsignificant). IBS-D also had shorter episodes (9 h 23 min) compared with IBS-M (15 h 01 min) and IBS-C (15 h 25 min) (P<0.04). Stool frequency and looser consistency were greater with IBS-D and similar between IBS-C and IBS-M. Abdominal pain was the greatest predictor of episode status. Diary card ratings of pain and stool frequency overestimate levels reported by EMA. CONCLUSIONS: Episodes of IBS are associated with greater pain (strongest relationship), bloating, and stress scores, and poorer global well-being. Compared with IBS-D, IBS-C and IBS-M are similar in clinical features. Patients overreport pain and stool frequency by diary compared with EMA.

Psychosocial factors are more important than disease activity in determining gastrointestinal symptoms and health status in adults at a celiac disease referral center.

BACKGROUND: The relative effects of clinical and psychosocial variables on outcome in celiac disease (CD) has not previously been reported. In adult patients with (CD), we studied the relationships among demographics, psychosocial factors, and disease activity with health-related quality of life (HRQOL), health care utilization, and symptoms. METHODS: Among 101 adults newly referred to a tertiary care center with biopsy-proven CD we assessed: (a) demographic factors and diet status; (b) disease measures (Marsh score, tissue transglutaminase antibody (tTG) level, weight change and additional blood studies); and (c) Psychosocial status (psychological distress, life stress, abuse history, and coping). Multivariate analyses were performed to predict HRQOL, daily function, self-reported health, number of physician visits, and GI symptoms (pain and diarrhea). RESULTS: Impaired HRQOL and daily function was associated with psychological distress and poorer coping. Self-report of poorer health was associated with poorer coping, longer symptom duration, lower education, and greater weight loss. More physician visits were associated with poorer coping, abnormal tTG levels, and milder Marsh classification. Greater pain scores were seen in those with higher psychological distress and greater weight loss. Finally, diarrhea was associated with greater psychological distress and poorer coping. CONCLUSIONS: In patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.

Cognitive factors affect treatment response to medical and psychological treatments in functional bowel disorders.

OBJECTIVES: For clinical trials in functional bowel disorders (FBD), the definition of a responder, one who meets the predefined criteria for a clinical response, is needed. Factors that determine clinical response aside from treatment itself are unknown. The aim of this study was to determine what baseline and post-treatment factors affect treatment response. METHODS: Females (n=397) with FBD entering a 12-week, four-arm, randomized NIH treatment trial (desipramine (DES), CBT, pill placebo, and education) were studied at baseline and after treatment. Demographic, clinical, psychosocial, and physiological variables were considered in the analysis. A responder was defined as a patient obtaining a score>3.5 on an averaged eight-item, five-point satisfaction-with-treatment questionnaire. Baseline and post-treatment logistic regressions were performed for each treatment condition to predict the responder outcome variable. RESULTS: Similar cognitive features predisposed participants to treatment response across the treatment conditions: sense of control over the condition, positive relationship with therapist or study coordinator, confidence in treatment, improvement in maladaptive cognitions, and quality of life during treatment. Demographic and clinical variables studied were not predictive. Some treatment-specific effects predicting responder status were noted, including a reduction in stool frequency with DES treatment and lack of abuse history in the placebo group. CONCLUSIONS: For medication, psychological, and placebo treatment in FBD, satisfaction with treatment depends on cognitive factors of confidence in treatments, perceived control over illness and symptoms, and reduction in negative cognitions related to symptom experience. Addressing these issues among patients with FBD may enhance treatment response to a variety of treatments.

Irritable bowel syndrome subtypes defined by Rome II and Rome III criteria are similar.

BACKGROUND: The implications of the Rome III recommendations to change the irritable bowel syndrome (IBS) subtype criteria for stool pattern are unknown. AIM: (1) Determine the level of agreement between Rome II and Rome III subtypes and (2) compare the behaviors of Rome II and Rome III subtypes over time. METHODS: Female patients (n=148) with Rome II defined IBS were prospectively tracked over 5 consecutive 3-month periods. At baseline, bowel habit reports on questionnaires were used to subclassify patients into Rome II and Rome III subtypes. Over the subsequent 15 months, bowel habit reports on diary cards were used to subclassify patients based on previously derived surrogate criteria into Rome II and Rome III IBS subtypes. RESULTS: The level of agreement between Rome II and Rome III subtype assignments was quite high (86.5%; kappa 0.79). The behavior of Rome II and Rome III subtypes over time was also similar in terms of subtype prevalence, subtype stability, and the proportion of subjects who met criteria for alternating irritable bowel syndrome. CONCLUSIONS: Rome II and Rome III IBS subtypes are in high agreement and behave similarly over time. Therefore, studies that used Rome II subtype criteria and studies that will use Rome III criteria will define comparable populations.

A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D. METHODS: Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured. RESULTS: Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 +/- 0.8/d to 1.4 +/- 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 +/- 0.7 to 3.8 +/- 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss. CONCLUSIONS: A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.

Not all side effects associated with tricyclic antidepressant therapy are true side effects.

BACKGROUND & AIMS: Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms. METHODS: Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires. RESULTS: Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting. CONCLUSIONS: Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with psychologic distress.

Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment.

BACKGROUND AND AIMS: Assessing health related quality of life (HRQOL) is becoming more important in research and clinical care. However, little information is available on the performance of HRQOL questionnaires for the functional bowel disorders (FBD). The aims of this study were to (a) understand the performance of the Sickness Impact Profile (SIP) and IBS-QOL for the functional bowel disorders at baseline and after treatment, (b) determine which HRQOL subscales best improve with treatment, (c) determine clinically meaningful improvement, and (d) determine the predictors of HRQOL at baseline and in response to treatment. METHODS: Women with moderate to severe FBD were evaluated using both medical (desipramine vs placebo) and psychological (cognitive-behavioral therapy vs education) treatments. Clinical and psychosocial questionnaires along with the SIP and IBS-QOL were given at baseline and after 12-wk treatment. RESULTS: (a) Patients with FBD experience functional limitations in social interactions, home management, and recreational activities, respond emotionally to the pain, feel helpless, out of control, depressed, and irritable, and perceive restrictions in lifestyle relating to toilet accessibility, and eating; (b) HRQOL is not different among the FBD diagnoses or IBS subgroups; (c) the IBS-QOL is more responsive to treatment than the SIP; (d) meaningful clinical improvement is 2.8 points for SIP and 14 for IBS-QOL; and (e) improvement is demonstrated primarily in psychosocial rather than physical domains. In addition, we found that expectation of benefit is greater for taking a pill over a psychological intervention, and the predictive effects of abuse history and pain on outcome is mediated by psychosocial factors. CONCLUSIONS: The data support the value of the IBS-QOL over the SIP, and provide new information on the profile of impairment in FBD, and the ways in which medical and psychological treatments produce improvement in HRQOL.

A survey on patient educational needs in irritable bowel syndrome and attitudes toward participation in clinical research.

BACKGROUND: The educational needs of patients with irritable bowel syndrome (IBS) are poorly understood and rarely studied. AIM: To determine the educational needs of IBS patients, regarding content, presentation format, and expectations from healthcare providers. METHODS: Fifteen functional GI clinic patients were asked open-ended questions to generate items for a questionnaire addressing the study aim. A total of 104 IBS patients received this questionnaire by mail (42 had declined to participate in a prior IBS study). To assess the frequency of endorsements and importance (on a scale of 1-3) of the items, an index was calculated (frequency of endorsements x mean rating per item, first priority scored 3, third priority scored 1). A higher index indicated greater endorsement based on frequency and rating of response. RESULTS: A total of 29 (28%) subjects (22 willing, 7 unwilling to participate previously in questionnaire research) completed the questionnaire (mean age, 42.6 years; SD, 14.2 years; 19 female, 10 male). The overall low response rate is likely related to the population studied; 40.4% of our study subjects have declined participation in prior research. The response rate of those who have previously agreed to participate was 36%. The typical response profile included: interest in learning disease management (index=1.4) and preference for information presented in person by an M.D. (2.4). Choice of presentation media included magazines (1.9), television (1.5), and Web sites (1.2). Doctors' qualities ranked high related to competency (0.8), allocation of sufficient time (0.7), and listening skills (0.4). Preferred incentives for research participation included a thank you note (0.4), summary of trial results (0.3), and monetary incentives (0.6). CONCLUSIONS: This qualitative study will provide pilot data for a national survey on the educational needs of IBS patients, for use in developing effective patient-centered, educational programs.

Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage.

BACKGROUND: As shown in the per protocol analysis of a recent randomized, controlled trial, when tolerated, Desipramine (DES) is effective over placebo (PLA) in treating moderate-to-severe functional bowel disorders (FBD). Clinical experience suggests that the benefit from tricyclic antidepressants (TCA) in FBD can be achieved at doses lower than those used to treat major depression. Within psychiatry, when using higher dosage of TCAs, plasma levels can be used to adjust daily dosage to optimize a treatment response. However, in FBD, it is not known whether plasma levels at the lower dosage are similarly related to a clinical response. AIM: To determine in treating FBD, whether DES blood levels or dose taken can predict a clinical response. METHODS: As part of a study of 12 wk of antidepressant and psychological treatment in 431 patients with FBD at UNC and U of Toronto, we studied those participants who completed treatment (per protocol analysis) taking DES (N = 97, dose 50-150 mg/day) or pill placebo (PLA) (N = 55 1-3 pills/day). The primary outcome measure was defined as a composite score (Satisfaction with Treatment, McGill Pain Questionnaire, Global Well-being, and IBS-QOL). The composite score was correlated with: (i) DES plasma levels at week 6, and (ii) number of pills taken over the duration of the 12-wk treatment period. In addition, we also compared DES dose with DES plasma levels. RESULTS: There was a modest correlation between mean DES dose at weeks 5 and 6 and DES blood level at week 6 (R = 0.2 p < 0.07). However, there were no significant correlations between the composite score either with DES dose or with DES blood levels. CONCLUSIONS: Detectable blood levels of DES are associated with a clinical response in FBD. However, with dosages up to 150 mg, there is no relationship between total dose or plasma level and the clinical response.

A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.