Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

INTRODUCTION: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled. METHODS: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year). RESULTS: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6]). DISCUSSION: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

Training therapists to work with people with intellectual disability in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Current policy in the England suggests that people with intellectual disabilities should, where possible, access mainstream mental health services; this should include access to mainstream therapy services. It is likely that mainstream therapists will need training and support to work with people with intellectual disabilities. METHOD: Sixty-eight therapists working in an English Improving Access to Psychological Therapies (IAPT) service received one- or 2-day training on working with people with intellectual disabilities. Measures of confidence, general therapeutic self-efficacy and attitudes to people with intellectual disabilities' use of mainstream mental health services were completed pre-training, post-training and at 3-month follow-up; at which time, 12 participants were interviewed about the impact of the training on their practice. RESULTS: There was a significant positive change in all measures immediately post-training which was maintained at 3-month follow-up. CONCLUSIONS: Training considerations for mainstream therapists who may work with people with intellectual disabilities are discussed.

The Development of a Measure of Confidence in Delivering Therapy to People with Intellectual Disabilities.

UNLABELLED: Current policy in UK health services emphasizes that, where possible, people with intellectual disabilities should access the same services as people without intellectual disabilities. One of the barriers to this is the confidence of clinicians and therapists. In this paper, we report on the development of a scale to describe the confidence of therapists in working with people with intellectual disabilities (the Therapy Confidence Scale-Intellectual Disabilities [TCS-ID]). One-hundred and eighty-one therapists who provided talking therapies but who did not work primarily with people with intellectual disabilities completed the scale; 43 people completed the scale twice for test-retest reliability purposes. One-hundred and seven people also completed a scale of general therapy self-efficacy. The TCS-ID has a single factor structure accounting for 62% of the variance, Cronbach's alpha for the scale is 0.93 and test-retest reliability is 0.83. There are significant differences in confidence based upon participants experience in working with people with intellectual disabilities and their therapeutic orientation, and there is a significant association between the TCS-ID and the General Therapy Self-efficacy Scale. Sixty clinicians working in mainstream mental health services received training on adapting their therapeutic approaches to meet the needs of people with intellectual disabilities. The TCS-ID was used pre-training and post-training and demonstrated a significant increase in confidence for all group. We suggest that the scale has good psychometric properties and can be used to develop an understanding of the impact of training for mainstream therapist in working with people with intellectual disabilities. KEY PRACTITIONER MESSAGE: There is increasing emphasis on people with intellectual disabilities receiving services from mainstream mental health services. There is no research describing the experiences and outcomes of people with intellectual disabilities receiving mainstream talking therapy services. The confidence that clinicians have in working with people with intellectual disabilities may be a barrier to them receiving mainstream services. The Therapy Confidence Scale-Intellectual Disabilities is a psychometrically sound scale for measuring the confidence of therapists in working with people with intellectual disabilities and is a useful outcome measure for training clinicians to work with people with intellectual disabilities.

Simultaneous double hemodialysis for the control of refractory hyperammonemia.

INTRODUCTION: In adults, hyperammonemia is generally associated with hepatic dysfunction or as a complication of urinary diversions when infected or obstructed. Hyperammonemia has also rarely been reported in association with multiple myeloma. With modest elevations, hyperammonemia often leads to encephalopathy. However, when ammonia reaches extreme levels cerebral edema and herniation may occur leading to coma, seizures, or death. CASE: We describe a 72-year-old Caucasian male with a history of end-stage renal disease (ESRD) and multiple myeloma who developed profound encephalopathy and eventual obtundation. He was found to have severe hyperammonemia that was not due to any identified hepatic impairment. His hyperammonemia proved to be refractory to medical therapy with cathartics and antibiotics, prolonged high-flux hemodialysis, and even continuous venovenous hemodialysis (CVVHD). This metabolic derangement as well as encephalopathy was eventually reversed with simultaneous CVVHD and extended daily hemodialysis (EDD). A more durable response was achieved after vincristine and dexamethasone were administered, which allowed the patient to resume his previous intermittent hemodialysis (IHD) schedule. The patient regained his full sensorium and was eventually discharged to home. CONCLUSIONS: Simultaneous double hemodialysis may be used as an important adjunct in treating refractory hyperammonemia.

A case of an isolated gastric variceal bleed secondary to a pancreatic neuroendocrine tumour.

Gastric varices are an important complication of portal hypertension. We present here a case of bleeding gastric varices secondary to a pancreatic neuroendocrine tumour. To our knowledge, there are no other reports in the literature. Such cases are always a timely and important reminder of the importance in considering causes of portal hypertension other than cirrhosis, particularly in patients with limited risk factors for liver disease.

Validity of the Rockall scoring system after endoscopic therapy for bleeding peptic ulcer: a prospective cohort study.

BACKGROUND: The Rockall scoring system was developed in unselected patients, the majority of whom did not receive endoscopic therapy. The aim of this study was to assess the validity of the Rockall system in high-risk patients who undergo endoscopic therapy for peptic ulcer hemorrhage. METHODS: Rockall scores were calculated in 247 patients with major peptic ulcer bleeding entered into a randomized trial of endoscopic therapy. The observed rates of recurrent bleeding and mortality after endoscopic therapy were compared with predicted rates derived from Rockall's study group. The validity of the Rockall system was assessed in terms of calibration and discrimination. RESULTS: Rates of recurrent bleeding and mortality after endoscopic therapy increased with an increasing Rockall score. Observed rates of recurrent bleeding and mortality were below predicted rates, and calibration of the Rockall system was poor (Mantel-Haenszel chi square = 25.8, p < 0.0001 for recurrent bleeding; Mantel-Haenszel chi square = 15.1, p < 0.0001 for death). For the prediction of recurrent bleeding, the area under the receiver operating characteristic curve was low (63.4%), but the system was satisfactory when predicting mortality (area under the resulting curve, 84.3%). CONCLUSIONS: After endoscopic therapy for a bleeding peptic ulcer, the Rockall scoring system can identify patients at high risk of death, but it is inadequate for the prediction of recurrent bleeding.

Guaiac versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community.

OBJECTIVE: To describe patient participation and clinical performance in a colorectal cancer (CRC) screening program utilising faecal occult blood test (FOBT). METHODS: A community-based intervention was conducted in a small, rural community in north Queensland, 2000/01. One of two FOBT kits--guaiac (Hemoccult-II) or immunochemical (!nform)--was assigned by general practice and mailed to participants (3,358 patients aged 50-74 years listed with the local practices). RESULTS: Overall participation in FOBT screening was 36.3%. Participation was higher with the immunochemical kit than the guaiac kit (OR=1.9, 95% CI 1.6-2.2). Women were more likely to comply with testing than men (OR=1.4, 95% CI 1.2-1.7), and people in their 60s were less likely to participate than those 70-74 years (OR=0.8, 95% CI 0.6-0.9). The positivity rate was higher for the immunochemical (9.5%) than the guaiac (3.9%) test (chi2=9.2, p=0.002), with positive predictive values for cancer or adenoma of advanced pathology of 37.8% (95% CI 28.1-48.6) for !nform and 40.0% (95% CI 16.8-68.7) for Hemoccult-II. Colonoscopy follow-up was 94.8% with a medical complication rate of 2-3%. CONCLUSIONS: An immunochemical FOBT enhanced participation. Higher positivity rates for this kit did not translate into higher false-positive rates, and both test types resulted in a high yield of neoplasia. IMPLICATIONS: In addition to type of FOBT, the ultimate success of a population-based screening program for CRC using FOBT will depend on appropriate education of health professionals and the public as well as significant investment in medical infrastructure for colonoscopy follow-up.

Clinical and endoscopic features of eosinophilic esophagitis in adults.

BACKGROUND: Eosinophilic esophagitis in adults is regarded as unusual, being diagnosed mostly in young men presenting with dysphagia. Mucosal furrows are a sentinel endoscopic feature. This study examined the demographic and clinical profile of adults with eosinophilic esophagitis seen from 1981 to 2002. METHODS: All patients from an Australian provincial city (population 198,000) with otherwise unexplained eosinophilic inflammation of the squamous epithelium (>/=30 eosinophils per high-power field) were included in a retrospective review. RESULTS: A diagnosis of eosinophilic esophagitis was made in 31 patients (24 men, 7 women; mean age 34 years, range 14-77 years). The diagnosis was made in 19 (61%) of the 31 patients during the most recent 2 years (none between 1981 and 1994 vs. 12 between 1995-2000 vs. 19 between 2000-2001). Esophageal mucosal furrows were present in 30 (97%), a finding infrequently recognized before 2001. Dysphagia was documented in 26 (89%). Symptoms had been present for long periods before diagnosis (mean 54 months; range 0-180 months), and diagnosis was delayed in 7 (mean 81 months, range 20-144 months) because sentinel features were overlooked at endoscopy. Strictures, often evident only as a result of mucosal shearing during dilation, were present in 17 (57%). Esophageal dilation preformed in 17 (mean 3.4 dilations per patient, range 1-13) consistently relieved symptoms; tears were recorded in 13 (87%), but no serious complication resulted. CONCLUSIONS: Eosinophilic esophagitis in adults of all ages is more common than recognized. Mucosal furrows are easily overlooked at endoscopy although this finding is an important clue to diagnosis. Strictures, a frequent consequence, can be safely managed by dilation.