Maria Eugenicos

Inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD): clinical features including sphincter disturbance in a large pedigree

Autosomal dominant inclusion body myopathy (IBM) associated with Paget disease of bone (PDB) and frontotemporal dementia (FTD), or IBMPFD, is a rare recently described multisystem disorder caused by missense mutations of the valosin-containing protein (VCP) gene on chromosome 9p13–p12 (OMIM 605382).1 Recognised features include proximal and distal weakness, early-onset PDB, early-onset FTD and cardiomyopathy.1–3 Here we report the clinical features of a large affected kindred. A large extended British family was identified with the condition (VS and AJ). Clinical information was obtained by interviewing patients, neurological examination of five living patients and reviewing medical records. Patients were investigated where possible with MRI of brain, spine and pelvic muscles, neurophysiology and anorectal physiology, muscle biopsy, Addenbrookes Cognitive Examination—Revised, skull, lumbar spine and pelvic x rays, creatine kinase and alkaline phosphatase. Mutation analysis of VCP was performed on four affected members and one unaffected reference member from this family. Genomic DNA, extracted from peripheral blood via standard methods, was analysed in duplicate for each subject. VCP mutation analysis of four affected individuals (II:18, III:13, III:14, III:15; online figure 1) showed a heterozygous c.464G→A nucleotide substitution in exon 5 of the VCP protein (p.R155H), a substitution not detected in an unaffected maternal brother (II:20) confirming mutation segregation within the family. This mutation has been previously identified.1 The pedigree of this five-generation IBMPFD family with 18 affected …

OC-066 Economic and quality-of-life burden of moderate-to-severe irritable bowel syndrome with constipation (ibs-c) in the uk: the ibis-c study

Introduction This is the first study to assess the burden of IBS-C in 6 European countries (France, Germany, Italy, Spain, Sweden, UK). Here we present the results for the UK. Method Observational, retrospective-prospective (6 months each) study in patients (pts) diagnosed with IBS-C in the last five years (Rome-III criteria) and moderate-to-severe symptoms at baseline: IBS-Symptom Severity Score (IBS-SSS) ≥175. Health resource utilisation was retrospectively and prospectively assessed. Symptom evolution was assessed in the prospective period, and quality-of-life (QoL) was assessed at baseline with EuroQoL-5D (EQ-5D) and IBS-QoL. Work productivity was prospectively assessed using the Work Productivity and Activity Impairment (WPAI): IBS-C questionnaire. Results 104 pts were included (79% severe, mean age [± SD] 45.5 ± 14.6 yrs, 93% female). At baseline, symptom severity (IBS-SSS; severe >300) was 373.1 ± 82.5; presenteeism (WPAI:IBS-C; mean ± SD): 47.9% ± 28.7%; absenteeism: 8.4% ± 24.2%; work productivity loss: 51.5% ± 27.2%; daily activity impairment: 56.8% ± 29.6%. Mean IBS-QoL was 57.2 ± 24.2, (scale: 0–100 [best-to-worst]) and mean EQ-5D was 54.0 ± 23.3 (scale: 0–100 [worst-to-best]. 87.5% and 64.4% of pts reported moderate-to-severe problems in pain/discomfort, anxiety/depression respectively. Most prevalent symptoms were abdominal pain (92%) and bloating (91%). 70% pts consulted a GP, and 100% a gastroenterologist; mean: 6.2 and 2.7 visits, respectively. 24% pts required emergency department visits or hospitalisation (mean stay [95% CI]: 12 [2.5–21.1] days). 52% had a diagnostic test (mean [95% CI]: 3.6 [2.9–4.4]). 90% pts took prescription drugs for IBS-C. Mean (95% CI) annual direct cost for the NHS: £ 1753 (1251–2308); the mean pt cost: £ 315 (184–482). 51% of pts took sick leave (mean: 5.2 times; mean duration: 26 days) and 82% had productivity losses (mean: 162 h). Mean indirect costs were £ 3407 (2078–4977). Total costs amounted to £ 5443 (3970–7252)/year. Conclusion Moderate-to-severe IBS-C has a major impact on patient QoL, productivity, and healthcare resource utilisation. Disclosure of interest Y. Yiannakou Conflict with: Grants: Shire; Medtronic. Speaker fees: Almirall; Shire; Sucampo, M. Eugenicos Conflict with: Consultant/Advisory Board Member: Almirall; Astellas; Dr Falk Pharma; NAPP; and Shire, D. Sanders Consultant for: Almirall, A. Emmanuel Conflict with: Advisory Board and Educational Talk honoraria: Almirall., P. Whorwell Conflict with: Consultant/research grant support: Almirall; Chr. Hansen; Danone Research; Ironwood; Salix; Shire; Sucampo, F. Butt: None Declared, S. Bridger: None Declared, N. Arebi: None Declared, A. Millar Conflict with: The hospital received payment from Almirall for the conduct of the study, V. Kaushik Conflict with: Advisory Board and Educational Talk honoraria: Almirall. Meeting support: Cooks; Tillotts; AbbVie., M. Rance Employee of: Almirall, J. Mackinnon Employee of: TFS Develop S. L., contracted by Almirall S. A to conduct the study, J. Bertsch Employee of: TFS Develop S. L, contracted by Almirall S. A. to conduct the study, J. Fortea Employee of: Almirall, J. Tack Conflict with: Grants/research support: Abbott; Novartis; Shire. Honoraria/consultancy fees: Almirall; AstraZeneca; Danone; GI Dyamics; GlaxoSmithKline; Ironwood; Janssen; Menarini; Novartis; Rhythm; Shire; Takeda; Theravance; Tsumura; Will Pharma; Zeria. Speaker fees: Abbott; Almirall; AstraZeneca; Janssen; Menarini; Novartis; Shire; Takeda; Zeria.

Pilot study of Acceptance and Commitment Therapy for Irritable Bowel Syndrome: A preliminary analysis of treatment outcomes and processes of change

Background The aim of this study was to investigate the efficacy and proposed processes of change of acceptance and commitment therapy (ACT) in improving the outcomes of irritable bowel syndrome (IBS). Methods A total of 56 consecutive patients recruited from a specialist clinic were included in the study and completed an ACT treatment protocol (one-day group workshop plus self-help manual). Assessments of process (acceptance of IBS) and outcome variables (symptom severity, avoidance behaviours, quality of life, and gastrointestinal anxiety) were carried at four time points (assessment, pre-treatment, post-treatment, and follow-up). Results A significant increase in the acceptance of IBS and improvement in all outcome variables was observed from pre- to post-treatment and follow-up (effect sizes medium to large). Improvements in all outcomes were associated with increases in acceptance of IBS. Changes in acceptance of IBS from pre- to post-treatment were a significant predictor of improvements in outcomes from pre-treatment to follow-up. Conclusions Results support the efficacy of a brief ACT protocol in improving IBS outcomes and maintaining therapy effects at six-month follow-up. Preliminary support for the treatment process proposed was also found.

UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation

Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [−77.0 (−96.3, −57.7); p < 0.001; n = 124] and baseline to 52 weeks [−70.7 (−95.0, −46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice.

THE CLINICAL FEATURES AND PROGNOSIS OF SCAN NEGATIVE URO-NEUROLOGICAL DISORDERS

Background Studies from our group have shown that around half of patients presenting with cauda equina syndrome (CES) have normal imaging, many of whom may have evidence of a functional neurological disorder. We have also shown high rates of comorbidity of functional neurological disorders in patients with idiopathic chronic urinary retention (including Fowlers syndrome). Aims To determine what proportion of patients with ‘scan negative’ CES and chronic dysfunctional voiding have a functional disorder by clinical consensus. To determine distress, disability and ongoing symptoms in patients with ‘scan positive’ and ‘scan negative’ CES three months after symptom onset. To determine frequency of comorbid functional disorders, distress, disability and physical function in patients with voiding dysfunction and a control urological group. Project Plans: The Back or Leg Pain with Bladder symptoms study (BLB) study is a prospective case control study of all patients admitted with possible CES to the Western General Hospital, Edinburgh. The Overview of Comorbidity in Chronic Urinary Retention (OCCUR) study is a prospective cohort study and retrospective notes review of patients with Chronic Urinary Retention (including Fowlers syndrome) via the urodynamic clinics in Glasgow, Edinburgh and London.

PWE-251 Diagnosis and management of moderate-to-severe irritable bowel syndrome with constipation (IBS-C) in the UK: the IBIS-C study

Introduction The IBIS-C study assessed the burden of IBS-C in 6 European countries (France, Germany, Italy, Spain, Sweden, and UK). Here we present the diagnosis and management results for the UK. Method Observational study in patients (pts) diagnosed with moderate-to-severe IBS-C in the last five years (Rome-III criteria) with a 12-month follow-up (6 months retrospective and 6 months prospective, in order to assess health resource utilisation [HRU] prior to and after an active phase of the disease). Moderate-to-severe IBS-C was defined as an IBS-Symptom Severity Score (IBS-SSS) ≥175. Results 104 pts were included (79% severe, mean age [±SD] 45.5 ± 14.6 years old, 93% female). Mean time since diagnosis: 2.6 ± 4.0 years; mean symptom duration: 15.3 ± 14.9 yrs. Diagnostic procedures were highly variable; the most common were blood tests (72%), colonoscopy (69%), and abdominal ultrasound (55%). At inclusion the most prevalent symptoms were abdominal pain (92%) and bloating (91%). Main ongoing comorbidities were anxiety (50%), chronic pain (44%), headache (40%), insomnia (33%), or dyspepsia (31%). 52% of pts had an average of 3.6 ± 2.7 diagnostic tests during follow-up, the most common were haematology (29%) and clinical chemistry (29%) blood tests, and colonoscopy (13%). 93% of pts took prescription drugs (90% took prescription drugs for their IBS-C). The most common medication groups were: laxatives (81%), prokinetics (32%), antispasmodics (20%), and analgesics (18%) alone or in combination. Overall, 63% of pts took OTC medication for their IBS-C; the most common were laxatives (37%), prebiotics/probiotics (14%), and peppermint oil (14%). In addition, 36% of pts received complementary therapies. Overall, marginal improvement was noted in symptom severity (IBS-SSS total score) between baseline (373 ± 83) and the 6-month visit (324 ± 113). Conclusion Moderate-to-severe IBS-C symptoms often remain undiagnosed for many years and degree of control does not improve over time even though there is a high degree of prescription medication use. Consequently, moderate-to-severe IBS-C continues to be a burden despite the availability of therapeutic interventions. Disclosure of interest Y. Yiannakou Conflict with: Grants: Shire; Medtronic. Speaker fees: Almirall; Shire; Sucampo, M. Eugenicos Conflict with: Consultant/Advisory Board Member: Almirall; Astellas; Dr Falk Pharma; NAPP; and Shire., D. Sanders Consultant for: Almirall, A. Emmanuel Conflict with: Advisory Board and Educational Talk honoraria: Almirall., P. Whorwell Conflict with: Consultant/research grant support: Almirall; Chr. Hansen; Danone Research; Ironwood; Salix; Shire; Sucampo., F. Butt: None Declared, S. Bridger: None Declared, N. Arebi: None Declared, A. Millar Conflict with: The hospital received payment from Almirall for the conduct of the study, V. Kaushik Conflict with: Advisory Board and Educational Talk honoraria: Almirall. Meeting support: Cooks; Tillotts; AbbVie, M. Rance Employee of: Almirall, J. Mackinnon Employee of: TFS Develop S. L, contracted by Almirall S. A to conduct the study, J. Bertsch Employee of: TFS Develop S. L, contracted by Almirall S. A to conduct the study, J. Fortea Employee of: Almirall, J. Tack Conflict with: Grants/research support: Abbott; Novartis; Shire. Honoraria/consultancy fees: Almirall; AstraZeneca; Danone; GI Dyamics; GlaxoSmithKline; Ironwood; Janssen; Menarini; Novartis; Rhythm; Shire; Takeda; Theravance; Tsumura; Will Pharma; Zeria. Speaker fees: Abbott; Almirall; AstraZeneca; Janssen; Menarini; Novartis; Shire; Takeda; Zeria.