The Lourdes Pilgrimage and the Impact on Pilgrim Quality of Life.

Lourdes, France, is a major site of pilgrimage, particularly for Roman Catholics with illness. The direct impact of pilgrimage on pilgrim quality of life (QOL) has not previously been measured. The present study aimed to measure the impact of pilgrimage to Lourdes on QOL in self-defined "sick pilgrims".

Alcohol-Specific Mortality in People With Epilepsy: Cohort Studies in Two Independent Population-Based Datasets.

The risk of dying by alcohol-specific causes in people with epilepsy has seldom been reported from population-based studies. We aimed to estimate the relative risk of alcohol-specific mortality in people with epilepsy, and the extent to which problematic alcohol use was previously identified in the patients' medical records. We delineated cohort studies in two population-based datasets, the Clinical Practice Research Datalink (CPRD GOLD) in England (January 01, 2001-December 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (January 01, 2001-December 31, 2014), linked to hospitalization and mortality records.

Alcohol care teams: where are we now?

Alcohol consumption affects the risks of approximately 230 three-digit disease and injury codes in the International Statistical Classification of Diseases and Related Health Problems-10th Revision. The United Nations Sustainable Development Goals comprise 17 challenging goals with 169 targets, which the 193 Member States aim to achieve by 2030. Action to reduce the harmful use of alcohol, especially addressing global health inequalities, will contribute to achieving many of the health-related goals and targets.

Alcohol-Related Mortality in Patients With Psoriasis: A Population-Based Cohort Study.

Importance: People diagnosed with psoriasis have an increased risk of premature mortality, but the underlying reasons for this mortality gap are unclear.

Objective: To investigate whether patients with psoriasis have an elevated risk of alcohol-related mortality.

Design, Setting, And Participants: An incident cohort of patients with psoriasis aged 18 years and older was delineated for 1998 through 2014 using the Clinical Practice Research Datalink (CPRD) and linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records.

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α.

Background & Aims: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres.

Synchronous colonic lymphoma and adenocarcinoma in a patient with Crohn's disease, treated with thiopurine therapy and a TNFα inhibitor: a challenge to Occam's razor.

A 52-year-old man with Crohn's disease, treated with thiopurine therapy and a tumour necrosis factor (TNF) α inhibitor, attended for surveillance colonoscopy, which revealed a transverse colon mass. Biopsies of this lesion showed a diffuse large B-cell lymphoma. CT scan demonstrated this lesion, an additional caecal mass and multiple metastases.

Collaborative liver and psychiatry care in the Royal Bolton Hospital for people with alcohol-related disease.

Since 1990, the Royal Bolton Hospital has been evolving a patient-centred, collaborative, seamless, holistic, gastroenterology, psychiatry, community model of alcohol care, team working, governance, research, training, education and health promotion. The aim is to deliver an accessible, responsive, cost-effective, rolled-out service. Consultant gastroenterologists, a specialist liaison psychiatrist, psychiatric alcohol liaison nurse, gastroenterology-based liver nurse practitioner and ward nurses provide joint inpatient and outpatient care for people with alcohol misuse, especially alcohol-related liver disease.

5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk).

A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure-activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.

Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk).

A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK.

Itk kinase inhibitors: initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead.

Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.

Exploring possible mechanisms for primary bile acid malabsorption: evidence for different regulation of ileal bile acid transporter transcripts in chronic diarrhoea.

Objectives: Chronic diarrhoea resulting from primary idiopathic bile acid malabsorption (IBAM) is common, but its aetiology is largely unknown. We investigated possible mechanisms, first looking for common sequence variations in the cytoplasmic ileal bile acid-binding protein (IBABP, gene symbol FABP6), and secondly, determining the expression of ileal mucosal transcripts for the apical sodium-linked bile acid transporter (ASBT), IBABP, the putative basolateral transporters, OSTalpha and OSTbeta, and regulatory factors.

Methods: Genomic DNA was prepared from two cohorts of patients and two control groups; the promoter and exonic regions of FABP6 were sequenced.

Collaborative care for alcohol-related liver disease.

By implementing collaborative care for patients with alcohol misuse and alcohol-related liver disease, the Royal Bolton Hospital aimed to improve and coordinate their care by recruiting a multidisciplinary team and placing the patient at the centre of all efforts. There has been a marked improvement in the accuracy of the drinking histories taken, detoxification, dietary documentation, and patient and staff attitudes and confidence, with enhanced satisfaction in patients, their families and staff and improved accessibility and communication. We observed a considerable increase in the number of inpatient and outpatient referrals and believe that it is more effective to work together in a joint gastroenterology/psychiatry team.

Alcohol misuse in older people: heavy consumption and protean presentations.

Background: Alcohol misuse, especially binge drinking in young people, and alcoholic liver disease are major public health concerns. However, alcohol misuse in older people is underestimated and often goes undetected.

Objective: To document alcohol consumption and clinical presentation of alcohol misuse in hospital inpatients aged >or=60 years.

The synthesis and SAR of 2-amino-pyrrolo[2,3-d]pyrimidines: a new class of Aurora-A kinase inhibitors.

A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation.

Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists.

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors.

The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported.

Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist.

An investigation into the structure-activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC(50) values. A representative compound morpholinyl-4-piperidinylacetic acid derivative (13d: IC(50)=4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.

The discovery of orally active triaminotriazine aniline amides as inhibitors of p38 MAP kinase.

A new structural class of triaminotriazine aniline amides possessing potent p38 enzyme activity has been discovered. The initial hit (compound 1a) was identified through screening the Pharmacopeia ECLiPS compound collection. SAR modification led to the identification of a short acting triaminotriazine aniline methoxyamide (compound 1m) possessing in vitro and in vivo oral activity in animal models of acute and chronic inflammatory disease.

Functional dyspepsia: motor abnormalities, sensory dysfunction, and therapeutic options.

Functional dyspepsia is a common condition, but as yet, the underlying etiology is unclear. In this article, upper gastrointestinal motor and sensory physiology are reviewed and the current evidence for motor and/or sensory functional abnormalities causing dyspeptic symptoms is presented. The complex interrelationship between abnormal motor activity and sensation is explored, as well as the potential roles for autonomic dysfunction and psychological state in modulating gastrointestinal sensation and motor function.

Diagnosing coeliac disease by rectal gluten challenge: a prospective study based on immunopathology, computerized image analysis and logistic regression analysis.

The purpose of this study was to evaluate the use of rectal gluten challenge in the diagnosis of coeliac disease. A total of 103 patients with features suggestive of this diagnosis were prospectively enrolled into the study; a diagnosis of coeliac disease was based on strictly defined criteria used in judging the proximal jejunal biopsy. On that basis, 45 out of the 103 patients were deemed to have coeliac disease.