Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures

Measles virus (MV) can cause severe acute diseases as well as long-lasting clinical deteriorations due to viral-induced immunosuppression and neuronal manifestation. How the virus enters the brain and manages to persist in neuronal tissue is not fully understood. Various mutations in the viral genes were found in MV strains isolated from patient brains. In this study, reverse genetics was used to introduce mutations in the fusion, matrix and polymerase genes of MV. The generated virus clones were characterized in cell culture and used to infect rat brain slice cultures. A mutation in the carboxy-terminal domain of the matrix protein (R293Q) promoted the production of progeny virions. This effect was observed in Vero cells irrespective of the expression of the signaling lymphocyte activation molecule (SLAM). Furthermore, a mutation in the fusion protein (I225M) induced syncytia formation on Vero cells in the absence of SLAM and promoted viral spread throughout the rat brain slices. In this study, a solid ex vivo model was established to elucidate the MV mutations contributing to neural manifestation

Nuances of the psychogastroenterology patient: A predictive model for gastrointestinal quality of life improvement

BackgroundGastrointestinal conditions are multifactorial in nature, and certain patients can benefit greatly from brain–gut psychotherapies delivered by mental health professionals who specialize in psychogastroenterology. This study aimed to identify features associated with improvements in GI‐specific quality of life scores following behavioral health interventions (BHI). The second aim was to create a psychogastroenterology referral care pathway incorporating identified characteristics for greatest benefit from GI‐specific behavioral therapy.MethodsWe performed a prospective observational study of 101 (63 women; median age, 45 years) gastroenterology patients referred for psychogastroenterology consultation at a single center. Patients attended an average of seven sessions with a single GI psychologist where evidence‐based brain–gut psychotherapies were employed. GI‐specific quality of life (IBS‐QOL) and psychological distress (BSI‐18) were assessed before and after BHI. Patients completed self‐reported questionnaires. We performed a multivariable analysis to determine predictors associated with IBS‐QOL score improvement.Key ResultsA total of 53 (52.5%) patients experienced improvement in IBS‐QOL score. Patients with improved IBS‐QOL scores had significantly higher baseline BSI general domain T‐scores (61.9 vs. 56.9, P = 0.002). Female gender (odds ratio [OR], 3.2), pretreatment BSI somatization T‐score ≥63 (OR, 3.7), and a diagnosis of depression (OR, 4.2) were associated with greater odds of IBS‐QOL score improvement following BHI.Conclusions and InferencesWe identified factors associated with response to GI‐specific BHI to aid in optimizing the utilization of psychogastroenterology services and provide referring providers with information to inform treatment recommendations. Female patients with disorders of gut–brain interaction (DGBIs), high somatization, and depression should be considered a priority for brain–gut psychotherapies.Gastrointestinal conditions are multifactorial in nature, and certain patients can benefit greatly from brain–gut psychotherapies delivered by mental health professionals who specialize in psychogastroenterology. Females with disorders of gut–brain interaction, high somatization, and depression should be considered priority for brain–gut psychotherapies. Behavioral health outcomes were not limited to disease; patients with IBD should be routinely considered for referral. Optimizing utilization of GI‐specific behavioral health specialists for the best outcomes can maximize quality of life and disease experience, but also improve value‐based care.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151345/1/nmo13663.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151345/2/nmo13663_am.pd

Randomised clinical trial: the long‐term safety and tolerability of naloxegol in patients with pain and opioid‐induced constipation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108643/1/apt12899.pd

Changing perceptions and practices regarding aspirin, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs among US primary care providers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74775/1/j.1365-2036.2008.03836.x.pd

A comparison of three fingerstick, whole blood antibody tests for Helicobacter pylori infection: a United States, multicenter trial

We compared three whole blood antibody tests for Helicobacter pylori ( H. pylori ) in a United States, multicenter trial. Methods Patients referred for EGD at three medical centers were recruited. During EGD, biopsies were taken for histology and rapid urease testing (RUT). Immediately after endoscopy, patients underwent the antibody tests (FlexPack HP, Abbott Diagnostics; QuikVue, Quidel Corporation; AccuMeter, ChemTrak) using whole blood obtained by two to three fingersticks. Performance characteristics were calculated for each antibody test using the biopsy-based methods as a gold standard. Results A total of 131 patients participated; 50 (38%) patients had histological evidence of H. pylori infection. Using histology as a gold standard, the sensitivities of FlexPack HP, QuikVue, and Accumeter were 76%, 78%, and 84%, respectively. Specificity was 79% with FlexPack HP and 90% with QuikVue and Accumeter. There were no significant differences in the performance of the three antibody tests though there was a trend toward superior performance for AccuMeter compared to FlexPack HP ( p = 0.019 ). However, RUT proved superior to FlexPack HP using histology as a gold standard ( p = 0.008 ). Using either concordant histology and RUT results or a positive histology or RUT to define active H. pylori infection, there was no statistically significant difference between the antibody tests. Conclusions There were no statistically significant differences in the performance of the three antibody tests. These tests proved only marginally sensitive in detecting patients infected with H. pylori . Clinicians should be aware of the limitations of these tests, particularly when using them as a sole means of testing for H. pylori .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72148/1/j.1572-0241.1999.1135_x.x.pd

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134450/1/apt13807.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134450/2/apt13807_am.pd

Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea

BackgroundPatients with irritable bowel syndrome with diarrhea (IBS‐D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist, is approved for the treatment of IBS‐D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints.MethodsTwo double‐blind, placebo‐controlled, Phase 3 trials (IBS‐3001 and IBS‐3002) randomized patients meeting Rome III criteria for IBS‐D to twice‐daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1‐26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency‐free days, and adequate relief, and change from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements.Key ResultsThe studies enrolled 2428 patients. Eluxadoline increased Weeks 1‐26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency‐free days, and adequate relief. Changes from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo.Conclusions and InferencesData presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS‐D.Data presentation in radar plot format can facilitate evaluation of the diverse array of symptoms and outcomes that are relevant to a symptom‐based condition like irritable bowel syndrome with diarrhea (IBS‐D). In 2 Phase 3 trials, eluxadoline treatment improved stool consistency and frequency, abdominal pain, bloating and discomfort, feelings of urgency, global symptom score, and adequate relief. Radar plots provide a visual demonstration of improvements with eluxadoline across 13 endpoints encompassing the diverse constellation of symptoms experienced by patients with IBS‐D.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145265/1/nmo13331_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145265/2/nmo13331.pd

A randomized, controlled trial to assess a novel colorectal cancer screening strategy: the conversion strategy

Our study was a randomized, controlled trial to assess a novel strategy that provides comprehensive colorectal cancer screening in a single visit versus traditional sigmoidoscopy and, where appropriate, colonoscopy on a subsequent day. METHODS : Consecutive patients referred for screening were randomized to control or so-called “conversion” groups. Patients in the control group were prepared for sigmoidoscopy with oral phospho-soda. Those with an abnormal sigmoidoscopy were scheduled for colonoscopy on a future day after oral polyethylene glycol preparation. In the conversion group, patients were prepared with oral phospho-soda. Patients with a polyp >5 mm or multiple diminutive polyps were converted from sigmoidoscopy to colonoscopy, allowing comprehensive screening in a single visit. Clinical outcomes were assessed by postprocedure physician and patient questionnaires. RESULTS : Two hundred thirty-five patients were randomized (control = 121, conversion = 114). In the control group, 28% had an indication for colonoscopy. Three of 33 (9%) with an abnormal sigmoidoscopy did not return for colonoscopy. At colonoscopy, 27% had a proximal adenoma. In the conversion group, 28% had an abnormal sigmoidoscopy and underwent conversion to colonoscopy. Forty-one percent undergoing colonoscopy in the conversion group had a proximal adenoma. Physicians reported no differences in preparation or procedure difficulty, whereas patients reported no differences in the level of comfort or overall satisfaction between groups. When queried regarding preferences for future screening, 96% chose the conversion strategy. CONCLUSIONS : The conversion strategy led to similar outcomes compared to traditional screening while improving compliance with colonoscopy in patients with an abnormal sigmoidoscopy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73097/1/j.1572-0241.2000.02231.x.pd

Development and validation of the Patient‐Physician Relationship Scale among patients with irritable bowel syndrome

BackgroundAn effective patient‐physician relationship (PPR) is essential to the care of patients with irritable bowel syndrome (IBS). We sought to develop and validate an IBS‐specific instrument to measure expectations of the PPR.MethodsWe conducted structured focus groups about PPRs with 12 patients with IBS. Qualitative analysis was used to generate a questionnaire (the Patient‐Physician Relationship Scale [PPRS]), which was modified with input from content experts and usability testing. For validation, we administered it online to US adults with IBS. Participants also completed the Functional Bowel Disorder Severity Index, the Rome III Adult Functional gastrointestinal (GI) Disorder Criteria Questionnaire, and modified versions of the Communication Assessment Tool (CAT‐15) and Patient‐Doctor Relationship Questionnaire (PDRQ‐9). We performed principal components factor analysis for the PPRS.Key ResultsThe PPRS contained 32 questions with responses on a 7‐item Likert scale. Themes included interpersonal features, clinical care expectations, and aspects of communication. One thousand and fifty‐four eligible individuals completed the survey (88% completion rate). Most participants were middle aged (mean 48 years, SD 16.3), white (90%), and female (86%). Factor analysis showed only one relevant factor, relating to quality of PPR. The final scale ranged from possible‐96 to +96 (mean 62.0, SD 37.6). It correlated moderately with the CAT‐15 (r=.40, P<.001) and PDRQ‐9 (r=.30, P<.001), establishing concurrent validity.Conclusions & InferencesWe describe the development and validation of the first questionnaire for use in measuring patient expectations of the PPR, which can be used for future outcomes studies and training physicians.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138227/1/nmo13106.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138227/2/nmo13106_am.pd

The Chemtrak Hp Chek Fingerstick Whole Blood Serology Test for the Detection of Helicobacter pylori Infection

To evaluate a new whole blood serology test (Hp Chek; ChemTrak) that detects IgG antibodies to Helicobacter pylori . Methods : The study was conducted at 10 sites within the United States. Patients undergoing upper endoscopy for dyspepsia were recruited for enrollment. Those treated for H. pylori infection within a year of endoscopy and those who had regularly used proton pump inhibitors, bismuth compounds, or antibiotics within a month of endoscopy were not eligible. During endoscopy, specimens were obtained from the corpus and antrum for histological examination, which was performed by a single experienced pathologist. The Hp Chek was tested using whole blood and serum. Serum was also tested with a reference enzyme-linked immunosorbent assay (ELISA) at a centralized location. Test characteristics for the Hp Chek and ELISA were calculated using histology as the “gold standard.”. Results : Two hundred eighty-seven patients (140 women and 147 men; mean age 53 ± 6 yr ) were enrolled. The Hp Chek was easy to perform and yielded results 9 min after inoculation of the test cassette with whole blood or serum. When the Hp Chek used with whole blood was compared with histology as the gold standard, the sensitivity was 88%, specificity 85%, positive predictive value 83%, negative predictive value 90%, and percent agreement 86%. There were no statistically significant differences among the results obtained with the Hp Chek using whole blood, the Hp Chek using serum, or reference ELISA. Conclusions : The Hp Chek whole blood serology test was easy to perform and rapid and yielded performance characteristics comparable to those of a reference ELISA or the Hp Chek used with serum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75251/1/j.1572-0241.1998.016_c.x.pd