Ann Tierney

4-Liter Split-Dose Polyethylene Glycol Is Superior to Other Bowel Preparations, Based on Systematic Review and Meta-analysis

BACKGROUND & AIMS Adequate bowel cleansing is an important determinant of the efficacy of screening colonoscopy. Polyethylene glycol (PEG)-based solutions are used commonly in bowel preparation, but their poor palatability and large volumes (4 L) influence compliance. Adjunct therapies, such as bisacodyl, split-dose regimens, and lower-volume regimens have been tested. We performed a meta-analysis to determine whether a 4-L split dose of PEG is better than others for bowel cleansing before colonoscopy. METHODS We searched MEDLINE, the Cochrane Central Register of Controlled Trials and Database, recent abstracts from major conference proceedings, references from selected reviews and randomized trials (http://clinicaltrials.gov), and Google Scholar, through September 2011, for high-quality, randomized trials that compared 4-L split-dose PEG without adjunct therapy with other bowel preparation methods. Nine of 2477 trials considered were used in the analysis. We calculated pooled estimates of bowel preparation quality (primary outcome: excellent or good), preparation compliance, favorable overall experiences, willingness to repeat same preparation, and side effects. We calculated pooled estimates of odds ratios by fixed- and random-effects models. We also assessed heterogeneity among studies and publication bias. RESULTS The overall pooled odds ratio for excellent or good bowel preparation quality for 4-L split-dose PEG was 3.46, compared with other methods (95% confidence interval, 2.45-4.89; P < .01). Although there was significant heterogeneity in results among studies, 7 of 9 reported a significant benefit from the 4-L split-dose PEG preparation. There were no significant differences between PEG and others in preparation compliance, favorable overall experience, willingness to repeat the same preparation, abdominal cramping, nausea, or sleep disturbance. There was no significant publication bias based on funnel plot. CONCLUSIONS A meta-analysis showed that 4-L split-dose PEG is better than other bowel preparation methods for colonoscopy. Significant heterogeneity among studies might result from differences in patient demographics and protocols. A 4-L split dose of PEG should be considered the standard with which new bowel preparation methods are compared.

Nutrition environments in corner stores in Philadelphia

OBJECTIVE To examine the availability, quality, and price of key types of healthy and less-healthy foods found in corner stores in low-income urban neighborhoods and the associations between store characteristics and store food environments. METHOD A sample of 246 corner stores was selected from all corner stores participating in the Philadelphia Healthy Corner Store Initiative (HCSI). The Nutrition Environment Measures Survey for Corner Stores (NEMS-CS) was used to assess the availability, quality, and price of foods and beverages in 11 common categories between February and May, 2011. RESULTS NEMS-CS measures were completed in 233 stores, 94.7% of the 246 stores approached. The healthier options were significantly less available in all food categories and often more expensive. Baked goods, bread, chips and cereals were sold at nearly all stores, with significantly fewer offering low-fat baked goods (5.7%, p<0.0001), whole grain bread (56.2%, p<0.0001), or baked chips (35.2%, p<0.0001). Number of aisles was positively associated with availability score (p<0.05). CONCLUSION Findings from this study point toward potential targets for intervention to improve the corner store food environment and dietary choices among low-income urban populations. Availability of certain healthier foods could be improved.

Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study.

Summary A greater variability in a patients baseline 7‐day pain rating diary predicts an increased likelihood of placebo group response without affecting the active medication group response. ABSTRACT The degree of variability in the patient baseline 7‐day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). Our analysis demonstrated an increased likelihood of response in the placebo‐treated group for patients with a higher standard deviation in the baseline 7‐day diary without affecting the likelihood of a response in the active medication–treated group, confirming our hypothesis. In addition, there was a small but significant age‐by‐treatment interaction in the PHN model, and small weight‐by‐treatment interaction in the DPN model. The patients sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7‐day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.

Effect of the CCR5 antagonist maraviroc on the occurrence of immune reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind, randomised, placebo-controlled trial

BACKGROUND Immune reconstitution inflammatory syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in patients with HIV. IRIS is associated with an increased risk of admission to hospital and death. We assessed whether CCR5 blockade with maraviroc reduces the risk of IRIS. METHODS The CADIRIS study was a double-blind, randomised, placebo-controlled trial that recruited participants from five clinical sites in Mexico and one in South Africa and followed them for 1 year. Patients were eligible if they were adults with HIV, who were naive to ART, had CD4 count lower than 100 cells per μL and HIV RNA greater than 1000 copies per mL. Participants were randomly assigned (1:1) by permuted block randomisation to receive either maraviroc (600 mg twice daily) or placebo in addition to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Patients, care providers, and members of the research team were masked to treatment allocation. Clinical and laboratory evaluations were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary outcome was time to an IRIS event by 24 weeks. All patients who were randomly assigned contributed to the primary time-to-event analysis from the date of ART initiation until week 24, the time of an IRIS event or death. This trial is registered with ClinicalTrials.gov, number NCT00988780. FINDINGS Between Dec 10, 2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion criteria and three refused to participate; thus 276 participants were randomly assigned (140 to receive maraviroc and 136 to receive placebo). 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo group (p=0·74). No difference in the time to IRIS events was noted between the treatment groups (HR 1·08, 95% CI 0·66-1·77; log-rank test p=0·74). 37 participants (26%) in the maraviroc group had grade 3 or 4 adverse events compared with 24 (18%) in placebo group; p=0·072); 25 (18%) in the maraviroc group and 21 (15%) in the placebo group had serious treatment emergent adverse events (p=0·63). INTERPRETATION Maraviroc had no significant effect on development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in people with advanced HIV infection. FUNDING Pfizer.

Early Immunologic Failure is Associated With Early Mortality Among Advanced HIV–Infected Adults Initiating Antiretroviral Therapy With Active Tuberculosis

BACKGROUND The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART. METHODS We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ≤ 125 cells/µL. Purified protein derivative (PPD)-specific immune recovery was determined by interferon-γ enzyme-linked immunosorbent spot assays. Levels of interleukin 6, C-reactive protein, and soluble CD14 were assessed. Patients with CD4 count and viral load values at baseline and week 4 were analyzed using multiple logistic regression. RESULTS Early immunologic response, but not pre-ART CD4 counts or virologic response, was related to early mortality (8 [interquartile range {IQR}, -18 to 43] vs 68 [IQR, 24-131] cells/µL, P = .002). In a logistic regression model, every 20 cells/µL increase in the CD4 count from baseline to week 4 was independently associated with a 40% reduction in the odds of death (odds ratio, 0.59 [95% confidence interval, .41-.87]). PPD-specific immune recovery was lower, whereas levels of immune activation were higher, among deaths. CONCLUSIONS Early immunologic failure despite virologic suppression is associated with early mortality after ART initiation in advanced HIV/tuberculosis.

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus

Considerable variability exists in adherence to practice guidelines for Barretts esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.

Lactulose Hydrogen Breath Test Result Is Associated with Age and Gender

Small intestinal bacterial overgrowth (SIBO) is associated with chronic gastrointestinal diseases and structural/functional abnormalities of the gastrointestinal tract. SIBOs association with clinical characteristics is unclear. This study investigates the association between clinical factors and SIBO according to lactulose hydrogen breath test (LHBT) result. Methods. A cross-sectional study in a university-based gastroenterology practice was performed. Data was abstracted from the medical records of subjects undergoing LHBT from 6/1/2009 to 6/1/2013. Logistic regression analysis was performed to determine the association between predictor variables: age, sex, body mass index (BMI), and positive LHBT, the outcome of interest. Results. LHBT was performed in 791 subjects. Fifty-four percent had a positive LHBT. There was no statistically significant difference between the LHBT results according to age or BMI. In females, the likelihood of a positive LHBT increased with age (OR 1.02; 95% CI: 1.01–1.03). In males, the likelihood of a positive LHBT result decreased with age (OR 0.98; 95% CI: 0.97–1.00). Conclusion. There was an association between age, with respect to sex, and a positive LHBT. With increased age in females, the odds of a positive LHBT increased, while, in men, the odds of a positive LHBT decreased with age.

Su1147 Meta-Analysis of Overall Risk of Lymphoma in Patients With Inflammatory Bowel Disease on Thiopurine Therapy With Inclusion of European and North American Studies: Differences Between Referral Center Studies and Population Based Studies

BackgroundWith the ever increasing use of immunosuppressive therapy for the management of inflammatory bowel disease (IBD), patients are being exposed to infections which can be prevented by vaccinations administered prior to or during therapy. The European Crohns and Colitis Organisation guidelines currently recommend that IBD patients who receive immunosuppressive medications should be vaccinated yearly with the influenza vaccine and a pneumococcal vaccination 3-5 yearly. Several studies have demonstrated that despite guidelines many patients were still not being vaccinated for preventable disease. Method An audit was carried out within our department to assess our patients knowledge and uptake of such vaccines. Patients were identified from an established database and those receiving immunosuppressive therapy were invited to complete a questionnaire. Data gathered included age, gender, current treatment, awareness and uptake of vaccinations. Results A cohort of 88 patients on immmunosuppressive therapy were analysed. 61% of patients were female and 39% male. Patients ranged between 16-21 years (11%), 22-30 years (18%), 31-50 years (40%), 51-70 years (24%) and above 70 (7%). 59 (67%) patients had Crohns disease, 26 (29.5%) ulcerative colitis and 3 (3.5%) had indeterminate colitis. The majority of patients received immunomodulators including Azathioprine or Mycophenolate (n=48, 54%). 13 (15%) were treated with biologics alone (Infliximab or Adalimumab), 21 (24%) with combination of biologics and immunomodulators and 6 patients (7%) received immunomodulators with a reducing dose of steroids. 77% of patients were aware of recommended vaccinations but as many as 23% were not. 42% were aware of the importance of receiving dual vaccinations, 35% only aware of either the influenza or pneumococcal vaccine, with 23% unaware of the need for either. 54 (61%) patients had already had or were planning to have the influenza vaccine this year. Patients between the ages of 31-50 years had the highest awareness of the recommended vaccines (86%), with the majority of uptake of vaccines seen in the 31-50 year group (63%). Unfortunately 39% of patients were not receiving recommended vaccinations with more than half (56%) of patients being unaware of the need to avoid live vaccinations. Conclusions Our data suggest that a significant proportion of patients within our cohort are still not receiving vaccinations that were recommended to them. Although 77 % were aware of a form of recommended vaccine, 39% were not receiving them. Wider education of our IBD patients as well as their primary care doctors should be implemented to increase awareness and uptake of vaccines to provide adequate protection to this vulnerable group.

Changes in School Competitive Food Environments after a Health Promotion Campaign.

BACKGROUND Schools can reduce student access to competitive foods and influence healthy food choices by improving the school nutrition environment. This study describes changes in competitive nutrition environments in 100 K-8 schools participating in the Philadelphia Campaign for Healthier Schools. METHODS Interviews with school staff were used to elicit information about policies, practices, and guidelines to restrict/limit competitive foods in schools, before and 1 year into the campaign. To increase the validity of responses, respondents provided documentation for reported policies and guidelines. Baseline interviews were conducted between April and June 2011 and follow-up interviews were conducted between April and June 2012. RESULTS At follow-up, significantly more schools reported having policies and/or guidelines in place to regulate food as a reward in the classroom, food served at parties and celebrations, outside foods allowed in school, and the availability of sodas and sugar-sweetened beverages. There were no measurable effects on food available in school stores, fundraisers, or afterschool programs. Availability of concrete documentation of policies was limited, but when provided, it corroborated the interview responses. CONCLUSIONS In the context of a comprehensive school wellness policy, school wellness councils were associated with increases in school-level policies and practices that improved the competitive nutrition environment.

Infections in IBD Patients on Immunomodulators, Corticosteroids, and Anti-TNF therapy: Is Elderly Age a Predictor?

Background: Inflammatory bowel disease (IBD) therapy, including immunomodulatory (IMM), corticosteroids (CS), and TNF inhibitors (TNFI), is known to increase the infectious risk when used in to treat many diseases. No recent studies have analyzed the incidence of infections in elderly patients on these therapies. We aim to analyze the effect of immunosuppressant use and age on infectious complications in IBD patients. Methods: A retrospective cohort study was conducted of patients at a tertiary care center with Crohns disease (CD), ulcerative colitis (UC), or IBD, comparing infection risk in patients ≥65 years old to those < 65 years old. Chi-square and Wilcoxon Rank Sum statistics were performed. Infection rate ratio (IRRs) were evaluated. Results: 292 patients were assessed. 83% of patients < 65years old and 72% of patients ≥65years old were on immunosuppressant’s. Infections occurred in 41.4% patients. 7.8% of the cohort had ≥2 infections. The infection incidence rate per year of follow up in the younger and older cohorts were 0.106 and 0.170, respectively, with IRR of 1.60 (95% CI=1.16, 2.21) in the older. The IRR in elderly patients on CS compared to non-CS regimens was 3.28 (95% CI=1.62, 6.64). The IRR in elderly patients on IMM and CS, and on TNFI and CS were 10.58 (95% CI=1.27, 87.91) and 10.64 (95% CI=1.95, 58.10), respectively. Conclusions: Increasing age is associated with an increased risk for infections in IBD patients using immunosuppressive medications. CS had the highest IRR for infections compared to other therapies. Infectious risk is greatly increased when CS are added to IMM and TNFI. Correspondence to: Christina Tofani, MD, 132 S. 10th St., Main Building, Suite 480, Philadelphia, PA, USA, Tel: +1 215-662-4000; E-mail: christina.tofani@gmail.com