Juvenile cataract in association with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas occurring in multiple organ systems including the brain, kidneys, heart, lungs, liver, skin, and the eyes. Typical retinal findings associated with TSC include astrocytic hamartoma and achromic patch. While rare cases of cataract occurring in the setting of TSC have been reported, this is the first analysis of a large series of individuals with TSC that aims to quantify the frequency of this finding and to describe its clinical and genetic associations. MATERIALS AND METHODS: This is a retrospective chart review of 244 patients from the Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital who underwent complete ophthalmic examination. We describe the clinical and genetic findings in five individuals with TSC and juvenile cataract. RESULTS: Four of five cases (80%) were unilateral. The cataract was described as having an anterior subcapsular component in 3 of 5 cases (60%). Three individuals (60%) underwent lensectomy with intraocular lens (IOL) implant and two individuals (40%) were observed. Genetic testing revealed a known disease-causing mutation in TSC2 in 100% of cases. CONCLUSIONS: Recent evidence suggests that mTOR signaling may play a role in cataract formation which could explain the relatively high incidence of juvenile cataract in this population. Juvenile cataract is a potentially under-recognized ocular manifestation of TSC.

Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report.

BACKGROUND: Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. AIMS: To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. METHODS: This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. RESULTS: Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. CONCLUSIONS: Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting.

Obesity does not affect sodium picosulphate bowel preparation.

BACKGROUND: A previous study utilising oral polyethylene-glycol by Borg et al. concluded that obesity is an independent predictor of inadequate bowel preparation at colonoscopy. AIM: To compare bowel preparation quality between obese and non-obese individuals as assessed by Boston bowel preparation scale (BBPS) after using sodium picosulphate. METHODS: Prospective recruitment of patients at a day surgical unit in a New South Wales academic hospital. Bowel preparation was with Picoprep in all patients. Body Mass Index and epidemiological details were collected. Bowel preparation efficacy was assessed using the Boston Bowel Preparation Score. RESULTS: One hundred and four patients were enrolled prospectively. Five (4.8%) were excluded owing to poor mental capacity. Sixty-three (64%) were non-obese, and 36 (36%) were obese. Fifty-seven (90%) non-obese and 32 (89%) obese patients had good bowel preparation. There was no statistical difference for sodium picosulphate bowel preparation between obese and non-obese individuals (P > 0.99) using Fisher's exact probability tests. The BBPS score in the left colon predicted the overall BBPS score in all patients (P < 0.001). Three of 99 patients (3%) did not tolerate sodium picosulphate, with nausea being the most common side-effect. LIMITATIONS: Non-randomised study CONCLUSIONS: There was no difference in bowel preparation quality between obese and non-obese patients using a low-volume bowel preparation (sodium picosulphate) and without dose modification of the bowel preparation. Sodium picosulphate was a welltolerated and an effective bowel preparation for obese individuals. With an increasing incidence of obesity and expanding colonoscopic indications within Australia and other Western countries from government-sponsored programs, it is paramount that procedural quality not be compromised in the obese patient.

Changes in C-reactive protein during weight loss and the association with changes in anthropometric variables in men and women: LIFE Study.

OBJECTIVE: To investigate whether sex differences exist in the pattern of change in C-reactive protein (CRP) levels during weight loss, and whether the associations between weight change and CRP change differ by the types of anthropometric variables. DESIGN: Longitudinal, prospective analysis of subjects participating in an intentional weight loss trial (the Lose It For Ever: LIFE Study) followed-up for 30 months. SUBJECTS: A total of 212 healthy, obese men and women (age: 23-77 years, body mass index (BMI): 30-39 kg m(-2)) took part in this study. MEASUREMENTS: BMI, waist and hip circumferences, and waist-to-hip ratio, CRP and lifestyle variables repeatedly measured at baseline, 6, 12, 18 and 30-month follow-up. RESULTS: Weight change was J shaped with a nadir at 12 months in both men and women (P for month(2) <0.0001). CRP level was consistently higher in women than in men, but the differences were less prominent and were not statistically significant at 12- and 18-month follow-up. CRP changes between any two consecutive visits were significantly associated with changes in BMI during the same period in women. However, the associations between CRP changes and changes in waist or hip circumference were not as consistent, especially between 18- and 30-month follow-up when CRP significantly increased. The associations in men were generally similar among the different anthropometric measures. The association between changes in BMI and CRP was stronger in men than in women. CONCLUSION: BMI change generally correlated well with CRP changes in both men and women in the course of follow-up. Significant sex difference in CRP level at baseline diminished at 12- and 18-month follow-up, when both sexes had maintained the lost weight.

Are standard behavioral weight loss programs effective for young adults?

OBJECTIVE: To compare the enrollment, attendance, retention and weight losses of young adults in behavioral weight loss (BWL) programs with older participants in the same trials. METHODS: Data were pooled from three NIH-funded adult BWL trials from two clinical centers in different regions of the country (total N=298); young adults were defined as those aged 18-35 years. Both young adults and adults were compared on session attendance, retention at the 6-month assessment, weight loss and physical activity at 6 months. RESULTS: Young adults represented 7% of the sample, attended significantly fewer sessions than did adults (52 vs 74%, respectively; P<0.001) and were less likely to be retained for the 6-month assessment (67 vs 95%, respectively; P<0.05). Controlling for demographic variables, study and baseline weight, the mean weight losses achieved were significantly less for young adults compared with adults (-4.3 kg (6.3) vs -7.7 kg (7.0), respectively; P<0.05); fewer young adults achieved > or =5% weight loss at 6 months compared with older participants (8/21 (38%) vs 171/277 (62%); P<0.05). After controlling for session attendance, differences in the mean weight loss were not significant (P=0.81). Controlling for baseline values, study and demographics, changes in total physical activity over the initial 6 months of treatment were less for young adults compared with adults, but these differences only approached statistical significance (P=0.07). CONCLUSION: These data indicate that standard programs do not meet the weight control needs of young adults. Research is urgently required to improve recruitment and retention efforts with this high-risk group.

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).

Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.

BACKGROUND: Studies suggest that the positive predictive value of the Rome II criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red flags for detecting organic diseases in patients diagnosed irritable bowel syndrome by their physicians. METHODS: Systematic chart reviews were completed in 1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal pain, diarrhoea or constipation, who also completed questionnaires to identify Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome). Red flags were reported by 84% of the sample. The positive predictive value of individual red flags for identifying organic disease was 7-9%. Excluding any patient with a red flag improved the agreement between Rome II and clinical diagnosis by a modest 5%, but left 84% of patients who were diagnosed with irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS: Red flags may be useful for identifying patients who require additional diagnostic evaluation, but incorporating them into the Rome criteria would not improve sensitivity and would result in too many missed irritable bowel syndrome diagnoses.

Weight loss goals and treatment outcomes among overweight men and women enrolled in a weight loss trial.

Participants in weight loss programs typically set unrealistically high weight loss goals that some believe are detrimental to success. This study examined outcomes associated with goal and ideal body mass index (BMI). Participants (N=1801) were enrolled in a weight loss trial comprised of low-intensity mail or telephone interventions vs usual care. Goal and ideal weight losses were assessed by asking participants how many pounds they expect to lose in the program (goal) and how much they would like to weigh (ideal). Goal and ideal weight losses were unrealistically high (men: -16 and -19%, women: -21 and -27%). For women, less realistic goals were associated with greater weight loss at 24 months. Goals were not associated with participation or weight loss for men. Results are more supportive of the idea that higher goals motivate women to lose weight than of the hypothesis that high goals undermine effort.

The usual medical care for irritable bowel syndrome.

AIMS: To determine what constitutes usual medical care for irritable bowel syndrome, which patient characteristics influence choice of treatment and how satisfied patients are with care. METHODS: Patient encounters in a health maintenance organization were prospectively monitored to identify visits coded irritable bowel syndrome, abdominal pain, constipation or diarrhoea. Within 2 weeks these patients were sent postal questionnaires (n = 1770, 59% participation) to assess patient characteristics and treatment recommendations. Responders were sent follow-up questionnaires 6 months later (77% participation) to assess adherence and satisfaction with treatment. RESULTS: Treatments employed most frequently were dietary advice, explanation, exercise advice, reassurance, advice to reduce stress and antispasmodic medications. Primary care physicians and gastroenterologists provided similar treatments. Patient confidence was higher for lifestyle advice (63-67, 100-point scale) than for medications (46-59). However, adherence was greater for medications (62-79 vs. 59-69, 100-point scale). Satisfactory relief was reported by 57%, but only 22% reported that symptom severity was reduced by half. Usual medical treatment was less effective for irritable bowel syndrome than for constipation, diarrhoea, or abdominal pain. CONCLUSIONS: Usual medical care for irritable bowel syndrome emphasizes education and lifestyle modification more than drugs; patients have a greater expectation of benefit from lifestyle modification than drugs. Overall 57% of irritable bowel syndrome patients report satisfactory relief.

Binge eating disorder, weight control self-efficacy, and depression in overweight men and women.

OBJECTIVE: To examine binge eating, depression, weight self-efficacy, and weight control success among obese individuals seeking treatment in a managed care organization. DESIGN: Gender-stratified analyses of associations between binge eating, depression, weight self-efficacy, and weight change, using data from a randomized clinical trial that compared low-cost telephone-based, mail-based, and usual care interventions for weight loss. SUBJECTS: A total of 1632 overweight individuals (460 men, 1172 women; mean age: 50.7 y; mean body mass index: 34.2 kg/m(2)) were recruited from a large Midwestern US managed care organization. MEASUREMENTS: Height and weight were measured by study personnel at baseline, and self-reported weight was assessed at 6 and 12 months; self-reported depression status, binge eating, and self-efficacy for weight control were assessed at baseline. RESULTS: Lifetime prevalence rates for depression and probable binge eating disorder were high. Weight self-efficacy was inversely related to weight in both men and women. For women, depression was associated with lower weight self-efficacy and higher body weight. Women reporting depression or lower weight self-efficacy at baseline had less weight loss success at 6 and 12 months. Depression, binge eating disorder, and weight self-efficacy were not significantly associated with weight loss success in men. CONCLUSION: Negative emotional states are highly prevalent and predict poor treatment outcomes, particularly for obese women. As obese women with clinical depression typically are excluded from intervention studies, further research on how to address the intersection of obesity intervention and mood management may be warranted.

Costs of care for irritable bowel syndrome patients in a health maintenance organization.

OBJECTIVES: The aims of this study were: 1) to determine the total costs of care and costs related to lower GI-related problems for patients who received a diagnosis of irritable bowel syndrome (IBS), and 2) to compare them to age- and sex-matched population controls and patients treated for inflammatory bowel disease (IBD) or gastroesophageal reflux disease (GERD). METHODS: Use and cost data were obtained through the computerized information systems of a large staff-model health maintenance organization on three groups of patients diagnosed in 1994 or 1995 with IBS, IBD, or GERD; and an age- and sex-matched control group of patients without any of these listed diagnoses. The IBS patient group was compared to the three comparison groups on components of total and IBS-related costs. RESULTS: Total costs of care for IBS patients were 49% higher than population controls during the year starting with the visit at which IBS patients were identified. In the index year, every component of total costs except inpatient care was significantly higher for IBS patients than for population controls. The costs of care for lower GI problems were significantly higher for patients with IBS than for population controls across a range of services. However, only 33% of the difference in total costs of care between IBS patients and population controls was due to lower GI-related services in the index year. In the subsequent years, lower GI-related services accounted for 18% and 20% of the total cost difference between IBS patients and population controls. The total costs of care as well as the components of costs of care were generally higher for IBD patients than for IBS patients, but were comparable for GERD and IBS patients. CONCLUSIONS: Patients with IBS show sustained increases in health care costs relative to population controls for both lower GI services and care unrelated to lower GI problems. However, the majority of the excess in health care costs resulted from medical care not directly related to lower GI problems.

Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology.

BACKGROUND & AIMS: Heredity has been suggested to explain the finding that irritable bowel syndrome (IBS) tends to run in families. Research in this area has been limited. The aim of the present study was to assess the relative contribution of genetic and environmental (social learning) influences on the development of IBS by comparing concordance rates in monozygotic and dizygotic twins to concordance between mothers and their children. METHODS: Questionnaires soliciting information on the occurrence of more than 80 health problems, including IBS, in self and other family members were sent to both members of 11,986 twin pairs. RESULTS: Analysis is based on 10,699 respondents representing 6060 twin pairs. Concordance for IBS was significantly greater (P = 0.030) in monozygotic (17.2%) than in dizygotic (8.4%) twins, supporting a genetic contribution to IBS. However, the proportion of dizygotic twins with IBS who have mothers with IBS (15.2%) was greater than the proportion of dizygotic twins with IBS who have co-twins with IBS (6.7%, P < 0.001), and logistic regression analysis showed that having a mother with IBS and having a father with IBS are independent predictors of irritable bowel status (P < 0.001); both are stronger predictors than having a twin with IBS. Addition of information about the other twin accounted for little additional predictive power. CONCLUSIONS: Heredity contributes to development of IBS, but social learning (what an individual learns from those in his or her environment) has an equal or greater influence.

Autonomic nervous system function in women with irritable bowel syndrome.

Autonomic nervous system (ANS) balance was assessed in women with and without irritable bowel syndrome (IBS) using laboratory tests of function (ie, expiratory/inspiratory ratio, Valsalva, posture changes, and cold pressor) and spectral and nonspectral measures of heart rate variability (HRV). Women with (N = 103) and without IBS (N = 49) were recruited, interviewed, then completed a laboratory assessment and wore a 24-hr Holter monitor Analysis using the entire sample showed little difference between IBS and control women and between subgroups with IBS on either laboratory measures or 24-hr HRV measures. However, analysis restricted to those women with severe IBS symptoms showed quite pronounced differences between two IBS subgroups on 24-hr HRV measures. Parasympathetic tone was significantly lower and ANS balance was significantly higher in the constipation-predominant compared to the diarrhea-predominant group. Subgroups of women with IBS do differ in ANS function as measured by 24-hr HRV; however, these differences are only apparent among women with severe symptoms. These findings point out the importance of considering symptom severity when interpreting studies of IBS.

Selective recall of gastrointestinal-sensation words: evidence for a cognitive-behavioral contribution to irritable bowel syndrome.

OBJECTIVE: Selective attention to GI sensations has been suggested as an important mechanism that affects symptom perception in patients with irritable bowel syndrome (IBS), but this hypothesis has not yet been tested empirically. Differential recall of words describing negative affect has been used to demonstrate that depressed patients selectively attend to negative affect words. This technique may be useful for examining selective attention to somatic sensations. The aim of this study was to determine whether patients with IBS demonstrate selective recall of GI sensations compared with neutral words and words describing respiratory sensations. METHODS: A total of 16 IBS patients, nine asthmatic patients (medical controls), and eight healthy controls were shown 10 GI sensation words or phrases, 10 respiratory sensation words or phrases, and 10 neutral words in random order for 3 s each. After a distraction task, subjects wrote down all of the words or phrases they could remember. RESULTS: As predicted, IBS patients were more likely to recall GI words than other categories. Asthmatic patients were more likely to recall respiratory words in comparison with healthy controls. CONCLUSIONS: IBS patients selectively recall words describing GI sensations; this suggests that they may selectively attend to GI sensations, thus supporting the cognitive-behavioral theory of IBS.

Intergenerational transmission of gastrointestinal illness behavior.

OBJECTIVE: Previous research, based on retrospective reporting, suggests that parental reinforcement and modeling may be important mechanisms in the development of gastrointestinal illness behavior in children and adults. The aim of this study was to determine the relationship between the illness behavior of parents, in the form of health care use for irritable bowel symptoms, and the illness behavior of their children, without relying on retrospective recall. METHODS: A comparison of two matched groups was made. Groups included 631 children of parents who were diagnosed with irritable bowel syndrome during 1 calendar yr and 646 children of parents matched by parental age, gender, and number of children in the family who did not receive an IBS diagnosis during the same 1 yr. Health care use and costs over a 3-yr calendar period for all children and their parents collected from the health care database of a large health maintenance organization were evaluated. RESULTS: Case children had significantly more ambulatory care visits for all causes (mean 12.26 vs. 9.81, p = 0.0001) and more ambulatory visits for gastrointestinal symptoms (0.35 vs. 0.18, p = 0.0001). Outpatient health care costs over the 3-yr period were also significantly higher for case than control children ($1979 vs. $1546, p = 0.0001). Controlling for the total number of ambulatory visits of the parents, excluding gastrointestinal visits, did not alter the findings. Gender of the IBS parent was not related to children's gastrointestinal visits. CONCLUSION: This study extends previous research by showing that specific types of illness behavior may be learned through modeling.

Increasing patient adherence to gastroenterology treatment and prevention regimens.

Many gastroenterology treatments would be minimally effective if patients did not adhere to prescribed therapeutic regimens. However, considerable evidence exists that patients often do not adhere. Factors associated with nonadherence include the physician's or other health care provider's behavior, the prescribed regimen, and the illness. These factors affect patient adherence such that: 1) patients do not have the skills or knowledge necessary to complete an assignment; 2) patients do not believe that they will be helped by the prevention or intervention activity, or they do not accept the activity because they do not believe that its value will outweigh its costs; and 3) patients' environments are not supportive of, or interfere with, adherence. Strategies that can increase adherence include attention to the physician/patient relationship, direct skill training, setting up a reward structure, and reminders, among others. Specific methods that gastroenterology health care providers can utilize to enhance adherence in their practice are presented.

The relationship between psychological distress and gastrointestinal symptoms in women with irritable bowel syndrome.

BACKGROUND: Individuals with irritable bowel syndrome (IBS) are reported to experience more symptoms compatible with psychopathologic disorders, abnormal personality traits, and psychological distress. Conversely, individuals with psychiatric disorders report higher levels of gastrointestinal (GI) symptoms compatible with IBS. Thus, psychological distress may contribute to GI symptoms in individuals with IBS. OBJECTIVES: To examine psychological distress in women with IBS, women with similar GI symptoms but not diagnosed (IBS nonpatients, IBS-NP), and asymptomatic Control women. METHODS: The women (N=97) were interviewed, completed questionnaires, and maintained daily diaries for 2 months. Across-women and within-woman analyses were used to calculate the results. RESULTS: The IBS and IBS-NP groups had a higher percentage of lifetime psychopathology and recalled psychological distress. At least 40% of the women in the IBS and IBS-NP groups had positive relationships between daily psychological distress and daily GI symptoms. CONCLUSIONS: Psychological distress is an important component of the IBS symptom experience and should be considered when treatment strategies are designed.

Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning.

While target-derived neurotrophins are required for the survival of developing neurons in the PNS, the functions of neurotrophins in the CNS are unclear. Mice with a targeted gene deletion of brain-derived neurotrophic factor (BDNF) exhibit a wide-based gait. Consistent with this behavioral evidence of cerebellar dysfunction, there is increased death of granule cells, stunted growth of Purkinje cell dendrites, impaired formation of horizontal layers, and defects in the rostral-caudal foliation pattern. These abnormalities are accompanied by decreased Trk activation in granule and Purkinje cells of mutant animals, indicating that both cell types are direct targets for BDNF. These data suggest that BDNF acts as an anterograde or an autocrine-paracrine factor to regulate survival and morphologic differentiation of developing CNS neurons, and thereby affects neural patterning.

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.