Ami D. Sperber

Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications

OBJECTIVE:The irritable bowel syndrome (IBS) and the fibromyalgia syndrome (FS) coexist in many patients. We conducted complementary studies of the prevalence of FS in IBS patients and matched controls, and of IBS in FS patients and the implications of concomitant IBS and FS on health-related quality of life (HRQOL).METHODS:A study of 79 IBS patients with 72 matched controls (IBS study), and a study of 100 FS patients (FS study). All participants underwent tests of tender point sites and threshold of tenderness and answered questionnaires including personal and medical history, GI symptoms, and indices of HRQOL.RESULTS:In the IBS study, 25 of the 79 IBS patients (31.6%) and 3 of the 72 controls (4.2%) had FS (p < 0.001). Statistically significant differences were found among the study groups in terms of global well-being (p < 0.001), sleep disturbance (p < 0.001), physician visits (p= 0.003), pain (p < 0.001), anxiety (p < 0.001), and global severity index (SCL-90-R) (p < 0.001), with patients with IBS and FS having the worst results. IBS patients had significantly more tender points than controls (p < 0.001). In the FS study, 32 of the 100 FS patients (32%) had IBS. Patients with both disorders had significantly worse scores for physical functioning (p= 0.030) and for all but one of a 16-item quality of life questionnaire.CONCLUSIONS:FS and IBS coexist in many patients. Patients with both disorders have worse scores on HRQOL indices than patients with either disorder alone, or controls. Physicians treating these patients should be aware of the overlap, which can affect the presentation of symptoms, health care utilization, and treatment strategies.

A comparative reappraisal of the Rome II and Rome III diagnostic criteria: are we getting closer to the 'true' prevalence of irritable bowel syndrome?

Objectives Revisions of the diagnostic criteria for irritable bowel syndrome have led to varying prevalence estimates. The Rome III criteria require a lower symptom frequency than Rome II (at least 10% of the time for Rome III, compared with at least 25% of the time for Rome II). In an epidemiological survey of a representative sample of Israeli adults using Rome II, we reported the prevalence for irritable bowel syndrome as 2.9%. The official Rome II integrative questionnaire, used for that study, enables a close approximation of Rome III rates, facilitating a retrospective comparison of these criteria. Methods A representative sample of 1000 adults was interviewed with a validated Hebrew version of the official Rome II integrative questionnaire. The data were re-evaluated retrospectively to compare the Rome II results with a close approximation of the new Rome III criteria. Results The prevalence rates for irritable bowel syndrome were 2.9 and 11.4%, respectively, for Rome II and Rome III. The corresponding consultation rates were 57.1 and 41.7%, indicating that the more strict Rome II criteria may select out a group of patients with more severe disease or greater psychosocial problems. Women made up 71.4% of irritable bowel syndrome by Rome II and 62.5% by Rome III. Conclusions In the present retrospective study, the prevalence rate for irritable bowel syndrome in our population is significantly higher by Rome III compared with Rome II. Rome III may more closely reflect the socioeconomic burden of irritable bowel syndrome compared with the overly strict Rome II. Prospective comparative studies should be conducted to confirm these results.

Cross-cultural variation in disease-related concerns among patients with inflammatory bowel disease

Abstract OBJECTIVE: The aim of this work was to study cross-cultural variations in the impact of inflammatory bowel disease (IBD) on health-related quality of life by an international comparison of disease-related concerns. METHODS: Item and factor scores on the Rating Form of Inflammatory Bowel Disease Patient Concerns and overall mean concern levels were compared by analysis of variance among 2002 IBD patients in eight countries. RESULTS: The overall level of concern varied from 51 out of 100 in Portugal to 19 in Sweden, with intermediate scores for Italy (43), Canada (40), United States (39), France (39), Austria (33), and Israel (25). Having surgery, an ostomy, the uncertain nature of the disease, and medication side effects were each rated among the first five in importance in six countries. Other items varied considerably. For example, concern regarding pain and suffering was high in Israel and low in Portugal, whereas concern over developing cancer was low in Italy. Concern over financial issues and access to high-quality health care were inversely associated with measures of national economic prosperity. CONCLUSIONS: 1) Cross-cultural comparisons of patient concerns related to IBD are feasible using translated scales. 2) Reporting tendencies vary greatly; within Europe, patients from southern countries report greater overall concern. 3) The complications and the variable evolution of disease elicit general concern, but the importance of specific issues varies among countries. 4) The reasons for national differences may have social, cultural, and/or economic determinants with relevance to the patient-physician relationship, patient education, and therapeutic decision making.

Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia

OBJECTIVE:The purpose of this study was to evaluate the utility of the Functional Bowel Disorder Severity Index (FBDSI) as a measure of severity of disease among patients with the irritable bowel syndrome (IBS) and matched controls.METHODS:A total of 75 IBS patients and 69 matched controls completed questionnaires on bowel symptoms, health status, quality of life, psychological distress, concerns, anxiety, and sense of coherence. All participants also were tested for fibromyalgia (FS), a functional disorder of the musculoskeletal system. All participants were administered a questionnaire that included the FBDSI. On the basis of their responses to the questionnaire, the controls were subdivided as healthy controls (n = 48) or IBS nonpatients (n = 21). On the basis of the FS classification, 75 IBS patients were subdivided as IBS only (n = 50) or IBS and FS combined (n = 25).RESULTS:The mean FBDSI score was higher for the IBS patients than the controls (100.5 ± 12.7 and 23.5 ± 3.9, respectively; p < 0.001). IBS nonpatients had an intermediate score of 42.3 ± 18.0. Patients with both IBS and fibromyalgia had the highest mean FBDSI score: 138.8 ± 31.5. There was no association between FBDSI and age or gender, but FBDSI was significantly associated with other measures of health status.CONCLUSIONS:An association was found between the FBDSI and IBS patient status: IBS nonpatients, patients with IBS only, and patients with both IBS and fibromyalgia had increasingly severe scores. The results provide support for the validity of FBDSI as a measure of illness severity in functional gastrointestinal disorders.

Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy.

SummaryAn 11-year-old boy with asthma had been receiving a controlled release theophylline preparation. He was prescribed fluvoxamine for a depressive disorder and within a week complained of severe headaches, tiredness and vomiting. His serum theophylline concentration had increased from 14.2 mg/L (shortly before fluvoxamine was started) to 27.4 mg/L. Fluvoxamine was withdrawn and theophylline concentrations decreased. Clomipramine was substituted for fluvoxamine with no further problems, and a later theophylline concentration was 13.7 mg/L. Competitive inhibition of hepatic microsomal enzymes by fluvoxamine may have been responsible for the elevated theophylline concentrations and toxicity observed in this case.

Nonspecific Intestinal Adsorption of Levothyroxine by Aluminum Hydroxide

PURPOSE To evaluate the adverse effect of aluminum hydroxide on levothyroxine pharmacokinetics in hypothyroid patients and study the mechanism of this effect. DESIGN An in vivo open study supplemented by in vitro experiments. SETTING A university hospital-based outpatient service. INTERVENTION Administration for 2 to 4 weeks of an aluminum hydroxide-containing preparation to patients balanced on replacement thyroxine therapy. MEASUREMENTS Serum thyrotropin (TSH). RESULTS A significant increase in serum TSH was observed during seven periods of aluminum hydroxide administration (7.19 +/- 1.3 versus 2.62 +/- 0.8 mU/L; P = 0.012). In vitro studies indicated a considerable nonspecific adsorptive capacity of aluminum hydroxide for thyroxine. CONCLUSIONS The results indicate an adverse effect of aluminum hydroxide on levothyroxine bioavailability through a mechanism involving nonspecific adsorption, or complexing, of levothyroxine to aluminum hydroxide. We recommend close monitoring of serum TSH levels in patients receiving oral thyroid hormone replacement therapy who concurrently take aluminum hydroxide-containing medications. Adjustment of the levothyroxine dose, or cessation of the antacid, may be necessary.

Development and Validation of the Rome IV Diagnostic Questionnaire for Adults

The Rome IV Diagnostic Questionnaires were developed to screen for functional gastrointestinal disorders (FGIDs), serve as inclusion criteria in clinical trials, and support epidemiological surveys. Separate questionnaires were developed for adults, children/adolescents, and infants/toddlers. For the adult questionnaire, we first surveyed 1,162 adults without gastrointestinal disorders, and recommended the 90th percentile symptom frequency as the threshold for defining what is abnormal. Diagnostic questions were formulated and verified with clinical experts using a recursive process. The diagnostic sensitivity of the questionnaire was tested in 843 patients from 9 gastroenterology clinics, with a focus on clinical diagnoses of irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD). Sensitivity was 62.7% for IBS, 54.7% for FD, and 32.2% for FC. Specificity, assessed in a population sample of 5,931 adults, was 97.1% for IBS, 93.3% for FD, and 93.6% for FC. Excess overlap among IBS, FC, and FD was a major contributor to reduced diagnostic sensitivity, and when overlap of IBS with FC was permitted, sensitivity for FC diagnosis increased to 73.2%. All questions were understandable to at least 90% of individuals, and Rome IV diagnoses were reproducible in ¾ of patients after one month. Validation of the pediatric questionnaires is ongoing.

The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review

Objectives The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence. Design Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined meta-prevalence estimate. The heterogeneity of studies was assessed. Results 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. Conclusions The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology.

Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes

The irritable bowel syndrome (IBS) is the best known of the functional gastrointestinal tract disorders. Many IBS patients have at least one co-morbid somatic complaint and many meet diagnostic criteria for other functional disorders. Patients with IBS and another functional disorder, in comparison with patients with IBS only, have more severe IBS symptoms, a higher rate of psychopathology, greater impairment of quality of life, and more illness-related work absenteeism. Estimates of the prevalence of IBS in patients with fibromyalgia range from 30-35% to as high as 70%. Studies of IBS among patients with chronic fatigue syndrome have reported a prevalence ranging from 35-92%. The prevalence of IBS among patients with chronic fatigue syndrome is reported to be 14%. IBS patients with other co-morbid functional disorders appear to manifest a greater degree of somatization. It has been suggested that the presence of multiple co-morbid disorders may be a marker for psychological influences on etiology. This raises the question of whether the functional syndromes represent the same pathophysiological process, i.e., are the same entity that has been separated into different clinical entities because of medical sub-specialization, or are indeed separate disorders. While the answer to this question awaits further research, it would appear that most functional patients who meet formal diagnostic criteria for more than one functional disorder manifest one disorder clinically more that the others and seek consultation differentially for that set of symptoms.

Unexpectedly low prevalence rates of IBS among adult Israeli Jews

Abstract  The irritable bowel syndrome (IBS) and other functional bowel disorders (FBDs) are common functional gastrointestinal disorders. The prevalence of IBS using Rome II criteria is generally lower than with previous criteria. The aim of this study was to determine the prevalence of IBS and other FBDs in the adult Israeli Jewish population, which has not been surveyed to date. A telephone survey was conducted on a representative sample of the study population provided by the Israel Ministry of the Interior. IBS and other FBDs were diagnosed by Rome II criteria. The study population was 981 individuals and the overall response rate was 54%. The mean age was 45.0 years and 55% were females. In all, 2.9% had IBS (females: 3.7%, males: 1.8%, P = 0.08). The rate increased to 4.1% when the Rome II diagnostic criteria were amended to include some chronic alternators who are not picked up by the original scoring system. Approximately 26% of the respondents had a functional lower gastrointestinal (GI) disorder (females: 32.1%, males: 17.7%, P < 0.0001). Prevalence rates for IBS among Israeli Jewish adults are lower than rates reported from most countries, despite the high level of stress resulting from Israels geopolitical circumstances. Possible reasons for this low prevalence are discussed.