Coronavirus disease 2019 communication: novel sign language system to aid surgical tracheostomy whilst wearing a respirator.

BACKGROUND: The coronavirus disease 2019 pandemic has necessitated rapid adaptations to all levels of clinical practice. Recently produced guidelines have suggested additional considerations for tracheostomy and advocated full personal protective equipment, including filtering facepiece code 3 masks. Air seal with filtering facepiece code 3 masks is often challenging, and full-face respirators and powered air-purifying respirators with hoods need to be employed. The infection prevention benefits of this equipment are accompanied by potential issues in communication. OBJECTIVE: In an attempt to minimise surgical error through miscommunication, the authors sought to introduce a simple sign language system that could be used as an adjunct during surgery. RESULTS: Following evaluation of pre-existing sign language platforms and consideration of multiple surgical factors, 14 bespoke hand signals were ultimately proposed. CONCLUSION: Whilst this novel sign language system aims to bridge the communicative gap created by additional personal protective equipment, further development and validation of the proposed tool might be beneficial.

Design of Treatment Trials for Functional Gastrointestinal Disorders.

This article summarizes recent progress and regulatory guidance on design of trials to assess the efficacy of new therapies for functional gastrointestinal disorders (FGIDs). The double-masked, placebo-controlled, parallel-group design remains the accepted standard for evaluating treatment efficacy. A control group is essential, and a detailed description of the randomization process and concealed allocation method must be included in the study report. The control will most often be placebo, but for therapeutic procedures and for behavioral treatment trials, respectively, a sham procedure and control intervention with similar expectation of benefit, but lacking the treatment principle, are recommended. Investigators should be aware of, and attempt to minimize, expectancy effects (placebo, nocebo, precebo). The primary analysis should be based on the proportion of patients in each treatment arm who satisfy a treatment responder definition or a prespecified clinically meaningful change in a patient-reported outcome measure. Data analysis should use the intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include secondary outcome measures to support or explain the primary outcome and an analysis of harms data. Trials should be registered in a public location before initiation and results should be published regardless of outcome.

The management of bifocal intracranial germinoma in children.

OBJECTIVES: Bifocal intracranial germinoma (BFG) is a tumour of the pineal and suprasellar regions, which is known to be highly radiosensitive. The definitive treatment and outcomes are not well defined, particularly in the paediatric population. We review our series of purely paediatric cases from a single institution and combine them with the limited reports in the literature to determine the results of different management strategies. METHODS: Four patients were treated at our institution with a median age of 15.3 years. A literature search identified a further 38 paediatric cases with a median age of 12.9 years. RESULTS: All four patients had normal serum and CSF tumour markers. One patient had a diagnosis made based on imaging findings of bifocal pineal and suprasellar lesions presenting with diabetes insipidus. Three others underwent biopsy. All had craniospinal radiotherapy, which has led to complete cure with no cases of progression at a mean follow-up of 3 years. The most common treatment modality in published cases is craniospinal irradiation. In the cases reviewed, limited radiation treatments (whole ventricle or focal) combined with chemotherapy regimens yield comparable outcomes where there is no spinal dissemination. Outcomes do not appear to be altered by biopsy in cases with negative tumour markers and characteristic imaging appearances. CONCLUSION: Patients who present with a classic appearance of germinoma, negative tumour markers and diabetes insipidus probably do not require a biopsy to confirm the diagnosis. No evidence of dissemination may obviate the need for craniospinal irradiation, but good quality long-term follow-up data are required to demonstrate the benefits of combined focal radiotherapy and chemotherapy regimes.

Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

BACKGROUND: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for inducing and maintaining remission of mild and moderately active ulcerative colitis (UC). When the proximal margin of inflammation is distal to the splenic flexure, 5-ASA therapy can be delivered as a rectal suppository, foam or liquid enema. OBJECTIVES: The primary objective was to assess the efficacy and safety of rectal 5-ASA for maintaining remission of distal UC. SEARCH METHODS: We searched MEDLINE (1966 to August 2012), the Cochrane Library (August 2012), abstracts from major gastroenterology meetings (1997-2011) and bibliographies of relevant publications to identify relevant studies. SELECTION CRITERIA: Eligible studies were randomized controlled trials comparing rectal 5-ASA to placebo or another active treatment for a minimum duration of six months. Symptom scores needed to be assessed in at least one study outcome. Patients had to be at least 12 years of age with disease extent less than 60 cm from the anal verge or distal to the splenic flexure, as determined by barium enema, colonoscopy or sigmoidoscopy. Patients were expected to be in remission prior to the treatment trial. DATA COLLECTION AND ANALYSIS: Study eligibility was independently assessed by three authors. Data were extracted using standardized forms by two independent reviewers, with inter-rater agreement assessed using Cohen's Kappa and disagreements resolved by consensus. In cases where clarification of study results or methodology was needed, corresponding authors were contacted. The methodological quality of each trial was assessed by the Cochrane risk of bias tool and by a 30-point scale developed and used previously by the authors. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) for continued clinical, endoscopic and histologic remission were estimated for comparisons between rectal 5-ASA and placebo or oral 5-ASA, and for comparisons among 5-ASA doses. Heterogeneity was assessed using the Chi(2) test and visual inspection of forest plots. If no significant heterogeneity was identified (P > 0.10 for Chi(2)) a fixed-effect model (Mantel-Haenstzel) was used. If heterogeneity was significant, a random-effects model was used. MAIN RESULTS: Nine studies (484 patients) met the pre-specified inclusion criteria (Kappa 1.00). Six studies were rated as low risk of bias. Three studies were rated as high risk of bias due to blinding (two open label and one single-blind). The total daily dose of rectal 5-ASA ranged from 0.5 g to 4 g, and dose frequency ranged from once to three times daily. 5-ASA was delivered as liquid enema in five studies or as a suppository in four studies. Follow-up ranged from 6 to 24 months. Rectal 5-ASA was significantly superior to placebo for maintenance of symptomatic remission over a period of 12 months.Sixty-two per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 30% of patients in the placebo group (4 studies; 301 patients; RR 2.22, 95% CI 1.26 to 3.90; I(2) = 67%; P < 0.01). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 144 events) and inconsistency (i.e. unexplained heterogeneity). Rectal 5-ASA was significantly superior to placebo for maintenance of endoscopic remission over a 12 month period. Seventy-five per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 15% of patients in the placebo group (1 study; 25 patients; RR 4.88, 95% CI 1.31 to 18.18; P < 0.05). There was no statistically significant difference in the proportion of patients who experienced at least one adverse event. Sixteen per cent of patients in the rectal 5-ASA group experienced at least one adverse compared to 12% of placebo patients (2 studies; 160 patients; RR 1.35, 95% CI 0.63 to 2.89; I(2) = 0%; P = 0.44). The most commonly reported adverse events were anal irritation and abdominal pain. No statistically significant differences between rectal and oral 5-ASA were identified for either symptomatic or endoscopic remission over a period of six months. Eighty per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 65% of patients in the oral 5-ASA group (2 studies; 69 patients; RR 1.24, 95% CI 0.92 to 1.66; I(2) = 0%; P = 0.15). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 50 events) and high risk of bias (i.e. both studies in the pooled analysis were open label). Eighty per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 70% of patients in the oral 5-ASA group (2 studies; 91 patients; RR 1.14, 95% CI 0.90 to 1.45; I(2) = 0%; P = 0.26). In two small trials, one comparing 2 g/day 5-ASA enemas to 4 g/day 5-ASA enemas and the other comparing 0.5 g/day 5-ASA suppositories to 1 g/day 5-ASA suppositories no dose response relationship was observed. AUTHORS' CONCLUSIONS: The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission of mild to moderately active distal UC. Well designed randomized trials are needed to establish the optimal dosing regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and to identify subgroups of patients who are more or less responsive to specific rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be more effective than either oral or rectal monotherapy for induction of remission. The efficacy of combination therapy for maintenance of remission has not been assessed and could be evaluated in future trials.

Regulation of hindbrain Pyy expression by acute food deprivation, prolonged caloric restriction, and weight loss surgery in mice.

PYY is a gut-derived putative satiety signal released in response to nutrient ingestion and is implicated in the regulation of energy homeostasis. Pyy-expressing neurons have been identified in the hindbrain of river lamprey, rodents, and primates. Despite this high evolutionary conservation, little is known about central PYY neurons. Using in situ hybridization, PYY-Cre;ROSA-EYFP mice, and immunohistochemistry, we identified PYY cell bodies in the gigantocellular reticular nucleus region of the hindbrain. PYY projections were present in the dorsal vagal complex and hypoglossal nucleus. In the hindbrain, Pyy mRNA was present at E9.5, and expression peaked at P2 and then decreased significantly by 70% at adulthood. We found that, in contrast to the circulation, PYY-(1-36) is the predominant isoform in mouse brainstem extracts in the ad libitum-fed state. However, following a 24-h fast, the relative amounts of PYY-(1-36) and PYY-(3-36) isoforms were similar. Interestingly, central Pyy expression showed nutritional regulation and decreased significantly by acute starvation, prolonged caloric restriction, and bariatric surgery (enterogastroanastomosis). Central Pyy expression correlated with body weight loss and circulating leptin and PYY concentrations. Central regulation of energy metabolism is not limited to the hypothalamus but also includes the midbrain and the brainstem. Our findings suggest a role for hindbrain PYY in the regulation of energy homeostasis and provide a starting point for further research on gigantocellular reticular nucleus PYY neurons, which will increase our understanding of the brain stem pathways in the integrated control of appetite and energy metabolism.

Canadian cost-utility analysis of initiation and maintenance treatment with anti-TNF-α drugs for refractory Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Symptoms include but are not limited to abdominal pain, nausea, emesis, and diarrhea. Anti-TNF-α drugs are increasingly being used in patients with CD who have inadequate response to conventional therapy. However, these medications are quite expensive. The objective of this study is to evaluate the cost-utility of two anti-TNF-α drugs (infliximab, adalimumab) for refractory CD. METHODS: A Markov model was used to estimate the costs and QALYs of three treatments (usual care, infliximab, adalimumab) over a 5 year time horizon. After initial treatment, patients achieve remission, achieve treatment response or remain in the drug refractory health state. Patients who achieve remission or treatment response are at risk of relapse each 3 month model cycle. Patients in the drug refractory health state either remain in the health state or have surgery in each cycle. Different costs and utility values were assigned to the various model health states. Model input parameters including initial response rates, relapse rates, utility values were derived from published literature. RESULTS: Usual care had both the lowest expected costs ($17,017) and QALYs (2.555), while infliximab had both the highest expected costs ($54,084) and QALYs (2.721). The incremental cost per QALY moving from usual care to adalimumab and from adalimumab to infliximab was estimated to be to be $193,305 and $451,165, respectively. CONCLUSIONS: Based on common willingness to pay thresholds, ant-TNF-α drugs would not be perceived as a cost effective treatment for refractory CD.

Quality of life in patients with immune-mediated inflammatory diseases.

There is no doubt that patients with immune-mediated inflammatory diseases (IMID) have a significantly impaired quality of life (QOL). Pain and disability often leave these patients helpless and frustrated. The recognition that addressing physical and psychological functioning plays a significant role in an overall treatment approach led to the inclusion of QOL measures as secondary outcomes in clinical trials with IMID patients. To that end, both generic and disease-specific instruments have been utilized. Measurement of health-related QOL (HRQOL) and patient-reported outcomes (PRO) in a controlled manner allows for better understanding of the correlation between different aspects of disease activity and QOL. In addition, the effects of different therapeutic options on HRQOL-related outcomes can be further evaluated. This 3-part section describes key QOL-related complaints of patients with IMID affecting joints, skin, or gut. An overview of the strengths and weaknesses of various commonly used HRQOL instruments is provided. Finally, the influence of anti-tumor necrosis factor-α agents on HRQOL outcomes, as assessed in recent clinical trials, is highlighted.

Development of the Crohn's disease digestive damage score, the Lémann score.

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.

Patient outcomes after anti TNF-alpha drugs for Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a relatively high prevalence rate in North America. More than 50% of CD patients require surgery at some stage of their disease. Anti-TNF-alpha drugs are increasingly being used in patients with CD who have had an inadequate response to conventional therapy. Treatment with anti-TNF-alpha agents aims at improving symptom control and reducing the need for hospitalization and surgery. This review examines the clinical effectiveness of three anti-TNF-alpha agents (infliximab, adalimumab and etanercept) in moderate and severe CD. The review further considers the evidence for the harms and benefits associated with switching from one anti-TNF-alpha agent to another and strategies to optimize the timing of therapy.

Survey of access to gastroenterology in Canada: the SAGE wait times program.

BACKGROUND: Assessment of current wait times for specialist health services in Canada is a key method that can assist government and health care providers to plan wisely for future health needs. These data are not readily available. A method to capture wait time data at the time of consultation or procedure has been developed, which should be applicable to other specialist groups and also allows for assessment of wait time trends over intervals of years. METHODS: In November 2008, gastroenterologists across Canada were asked to complete a questionnaire (online or by fax) that included personal demographics and data from one week on at least five consecutive new consultations and five consecutive procedure patients who had not previously undergone a procedure for the same indication. Wait times were collected for 18 primary indications and results were then compared with similar survey data collected in 2005. RESULTS: The longest wait times observed were for screening colonoscopy (201 days) and surveillance of previous colon cancer or polyps (272 days). The shortest wait times were for cancer-likely based on imaging or physical examination (82 days), severe or rapidly progressing dysphagia or odynophagia (83 days), documented iron deficiency anemia (90 days) and dyspepsia with alarm symptoms (99 days). Compared with 2005 data, total wait times in 2008 were lengthened overall (127 days versus 155 days; P<0.05) and for most of the seven individual indications that permitted data comparison. CONCLUSION: Median wait times for gastroenterology services continue to exceed consensus conference recommended targets and have significantly worsened since 2005.

Gastroscopy following a positive fecal occult blood test and negative colonoscopy: systematic review and guideline.

BACKGROUND: A sizeable number of individuals who participate in population-based colorectal cancer (CRC) screening programs and have a positive fecal occult blood test (FOBT) do not have an identifiable lesion found at colonoscopy to account for their positive FOBT screen. OBJECTIVE: To evaluate the evidence and provide recommendations regarding the use of routine esophagogastroduodenoscopy (EGD) to detect upper gastrointestinal (UGI) cancers in patients participating in a population-based CRC screening program who are FOBT positive and colonoscopy negative. METHODS: A systematic review was used to develop the evidentiary base and to inform the evidence-based recommendations provided. RESULTS: Nine studies identified a group of patients who were FOBT positive and colonoscopy negative. Three studies found no cases of UGI cancer. Four studies reported cases of UGI cancer; three found UGI cancer in 1% or less of the population studied, and one study found one case of UGI cancer that represented 7% of their small subgroup of FOBT-positive/colonoscopy-negative patients. Two studies did not provide outcome information that could be specifically related to the FOBT-positive/colonoscopy-negative subgroup. CONCLUSION: The current body of evidence is insufficient to recommend for or against routine EGD as a means of detecting gastric or esophageal cancers for patients who are FOBT positive/colonoscopy negative, in a population-based CRC screening program. The decision to perform EGD should be individualized and based on clinical judgement.

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis.

BACKGROUND: 5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. OBJECTIVES: A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC. SEARCH STRATEGY: Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings. SELECTION CRITERIA: Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded. DATA COLLECTION AND ANALYSIS: Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy). MAIN RESULTS: Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response. AUTHORS' CONCLUSIONS: Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

Urinary potassium is a clinically useful test to detect a poor quality diet.

Poor eating habits, a strong predictor of health outcomes, are not objectively assessed in routine clinical practice. In this study, we evaluated the use of urinary potassium (K(+)) as a means to identify people consuming a poor quality diet. Consecutive patients with kidney stones (n = 220), aged 18-50 y, from a population-based lithotripsy unit, collected a single 24-h urine sample to assess urinary K(+). They also completed a FFQ to derive the recommended foods score (RFS), an index of overall diet quality, and had their blood pressure, heart rate, weight, and height measured. Urinary K(+) was related positively with the intake of recommended food items, including vegetables, fruit, whole grains, low-fat dairy products, fish and poultry, and wine and negatively to those not recommended by current dietary guidelines, including red meat, fast food, and high-energy drinks. Urinary K(+) was also correlated with the RFS (r = 0.226; P < 0.001). Using a receiver operating characteristic curve, K(+) excretion values below the gender-specific median (men, 60 mmol/d; women, 41 mmol/d) were identified as the optimal cutoff values for a poor quality diet, indicated by the RFS. Higher urinary K(+) was inversely related to adjusted BMI (P-trend = 0.03), diastolic blood pressure (P-trend = 0.04) and heart rate (P-trend = 0.006), after controlling for potential confounders. Urinary K(+) provides a summary measure of diet quality, is significantly related to BMI, blood pressure, and heart rate, and may be useful clinically to detect poor dietary habits and monitor response to dietary interventions.

The effect of mesalazine therapy on quality of life in patients with mildly and moderately active ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient-reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalazine (mesalamine). AIM: To examine the effect of mesalazine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalazine dose and responder status on QoL parameters. METHODS: Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from two double-blind, randomized, multicentre, active-controlled trials assessing 2.4 and 4.8 g/day oral delayed-release mesalazine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose and response to therapy were examined. RESULTS: Mesalazine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P < 0.0001 for both). Improvement was greater for patients with moderate disease. Greater week 6 changes occurred in clinical responders than nonresponders (50.1 vs. 23.6 points, respectively; P < 0.0001). CONCLUSIONS: Delayed-release oral mesalazine produces significant clinical and statistical improvements in QoL of patients with UC by 3 weeks, with further improvement at 6 weeks.

Quality of life of patients with ulcerative colitis: past, present, and future.

Quality of life (QoL) is vitally important to patients with chronic illnesses such as ulcerative colitis (UC) and has been assessed in observational, cross-sectional, and cohort studies. However, relatively few clinical trials have evaluated the QoL of patients with UC. Recently, greater availability of the necessary tools has facilitated the undertaking of studies showing that QoL of patients with UC is reduced significantly compared with that of the general population. Studies using disease-specific instruments have identified disease severity as the strongest predictor of QoL, with other disease-related predictors including type of medical or surgical treatment and the efficacy, tolerability, and acceptability to patients of particular types of medical or surgical treatments. Other factors, such as comorbid medical or psychosocial problems and adherence to treatment, also affect QoL. Combined use of generic and disease-specific instruments in clinical trials can ensure that all clinically relevant unexpected events (generic instrument) and important improvement or deterioration (disease-specific instrument) are captured. For accurate outcomes assessment, the use of comprehensively validated instruments is critical. The need for the development and evaluation of new instruments will be determined by the mechanisms and targets of novel therapies. Ultimately, QoL assessment of effective therapies will play a strong role in pharmacoeconomic evaluations, providing health policy makers with the evidence to support the treatments that can most effectively normalize QoL through complete symptom resolution, minimal side effects, and convenient administration.

A comparison of autonomic function in patients with inflammatory bowel disease and in healthy controls.

We evaluated autonomic function, symptoms and psychological parameters in patients with ulcerative colitis (UC), Crohn's disease (CD) and matched controls to assess whether UC patients have greater basal sympathetic autonomic activity. Outpatients with UC (n = 15), CD (n = 13) and healthy controls (n = 28) underwent spectral analysis of heart rate variability to assess cardiac autonomic function, a methacholine challenge to assess cholinergic pulmonary responsiveness, and questionnaires assessing disease severity, anxiety and depression. UC but not CD patients had greater sympathetic activity than controls with increased absolute (6600 vs 5884; P = 0.04) and relative (62.8%vs 54.8%; P = 0.02) low frequency areas. This was not because of increased overall autonomic nervous system (ANS) activation and was independent of disease activity. In UC patients, trait (personality-related) anxiety correlated strongly with disease symptoms (R = 0.84; P < 0.001) and quality of life (R = -0.81; P < 0.001) while situational (state) anxiety did not. In CD patients, ANS measures were similar to controls and disease activity was unrelated to psychological measures. Cholinergic pulmonary responsiveness was normal in both UC and CD patients. UC patients have an increased sympathetic ANS activity which is independent of symptom severity. In these patients symptom severity is strongly associated with measures of personality related (but not current) anxiety.

Recommendations on chronic constipation (including constipation associated with irritable bowel syndrome) treatment.

While chronic constipation (CC) has a high prevalence in primary care, there are no existing treatment recommendations to guide health care professionals. To address this, a consensus group of 10 gastroenterologists was formed to develop treatment recommendations. Although constipation may occur as a result of organic disease, the present paper addresses only the management of primary CC or constipation associated with irritable bowel syndrome. The final consensus group was assembled and the recommendations were created following the exact process outlined by the Canadian Association of Gastroenterology for the following areas: epidemiology, quality of life and threshold for treatment; definitions and diagnostic criteria; lifestyle changes; bulking agents and stool softeners; osmotic agents; prokinetics; stimulant laxatives; suppositories; enemas; other drugs; biofeedback and behavioural approaches; surgery; and probiotics. A treatment algorithm was developed by the group for CC and constipation associated with irritable bowel syndrome. Where possible, an evidence-based approach and expert opinions were used to develop the statements in areas with insufficient evidence. The nature of the underlying pathophysiology for constipation is often unclear, and it can be tricky for physicians to decide on an appropriate treatment strategy for the individual patient. The myriad of treatment options available to Canadian physicians can be confusing; thus, the main aim of the recommendations and treatment algorithm is to optimize the approach in clinical care based on available evidence.

Validation of the mainland Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) for ulcerative colitis and Crohn's disease.

BACKGROUND: Inflammatory bowel disease affects the quality of a patient's life in many ways, but no validated instrument for measuring disease-specific quality of life in these patients is available for use in Mainland China. The aim of our study was to develop and validate the Mainland Chinese translation of the Inflammatory Bowel Disease Questionnaire for ulcerative colitis (UC) and Crohn's disease (CD) by assessing its construct validity, discriminant ability, reliability, and sensitivity to change. METHODS: We administered a developed Mainland Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ). Ninety-two Mainland Chinese patients (52 with UC and 40 with CD) completed the Mainland Chinese version of the IBDQ, the Chinese version of SF-36, and the global scale for general well-being. A subgroup of 71 patients also completed the Mainland Chinese version of the IBDQ and the global scales for general well-being on a second occasion. Clinical activity was assessed by the Walmsley and Harvey-Bradshaw simple indices. RESULTS: The Mainland Chinese IBDQ scores correlated well with the related SF-36 dimensional scores for all 4 domains (r = 0.51-0.82), SF-36 total scores (r = 0.58-0.87), the colitis activity index (r = -0.56-0.74), and the CD activity index (r = -0.64-0.78) as well as with the global scales. The Mainland Chinese IBDQ was able to discriminate between active and inactive disease. Cronbach's alpha was 0.95 in UC and 0.94 in CD. Test-retest reliability was excellent (intraclass correlation coefficient 0.69-0.93) when it was repeated in patients whose clinical activity index was stable. In contrast, there was a significant difference between the baseline and follow-up measurements in patients whose clinical activity index was changed. CONCLUSIONS: The Mainland Chinese IBDQ proved to be a valid, discriminative, and reliable instrument for assessing health-related quality of life in patients with UC and CD in Mainland China.

Design of treatment trials for functional gastrointestinal disorders.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.