Integrative analysis for finding genes and networks involved in diabetes and other complex diseases

An integrative analysis combining genetic interactions and protein interactions can be used to identify candidate genes/proteins for type 1 diabetes and other complex diseases

The ostomy leak impact tool: development and validation of a new patient-reported tool to measure the burden of leakage in ostomy device users

Abstract Background Leakage is a major concern for people who use a stoma, but people’s experience and its impact is not well understood. This study aimed to establish a definition of leakage through clinical and user input. This information was used to develop and validate a new measurement tool to understand the impact of leakage for people using a stoma appliance, in the UK, US, France, and Denmark. Methods Participants were recruited from a panel of users, hosted by Coloplast, that includes people who currently use Coloplast products. Six clinicians and 41 users took part in concept elicitation interviews. The qualitative findings were used to draft items. A panel of clinical experts was organized to develop and validate items (N = 6). Cognitive debrief interviews were conducted with five users in each country, which resulted in removing some items and revising the measure. A psychometric validation was conducted with 340 people in four countries whereby participants were asked to complete a series of measures online. Full psychometric analyses including validity and reliability were conducted. Results A final tool was established consisting of three domains related to the burden of leakage: “Emotional impact,” “Usual and social activities,” and “Coping and control.” Convergent validity was evaluated by benchmarking to existing health-related quality of life instruments (domains of SF-36 and Ostomy-Q). This showed high correlation between domains of the leakage tool and other measures, in particular for the Emotional impact domain when compared with SF-36 Emotional well-being and Ostomy-Q Confidence domain (p  0.92). Conclusion The study highlights how users define leakage and its impact in a way that is meaningful to them. This information has been used to develop an instrument to measure leakage which can potentially be used by clinicians and researchers. The instrument demonstrated evidence supporting its reliability and validity as an outcome measure to assess the impact of leakage in stoma care

Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction.

People suffering from neurogenic bowel dysfunction (NBD) and an ineffective bowel regimen often suffer from fecal incontinence (FI) and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI) has been shown to reduce these symptoms and improve quality of life.To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC).A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs), episodes of FI, urinary tract infections (UTIs), and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI), multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model.The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of £21,768 per patient was estimated for TAI versus continuing SBC alone.TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC

Tornado diagram.

<p>Tornado diagram.</p

Data and Markov model overview.

<p>The boxes represent the health states that a neurogenic patient can transition between after having failed standard bowel care (SBC) before and after 2007. SBC alone. After having failed SBC >6 months, a patient can either a) Resume SBC, b) Progress to SNS/SARS/ACE or d) Progress to stoma (absorbing state). TAI in combination with SBC. After having failed SBC >6 months, a patient can either a) Initiate Peristeen TAI, b) Resume SBC, c) Progress to SNS/SARS/ACE or d) Progress to stoma. <i>The model assumes that patients do not transition directly from SBC/TAI to stoma</i>. <i>Transition probabilities have been obtained for each 6-month model cycle using GoalSeek in Excel</i>.</p

Baseline demographics of real-life data from 227 patients.

<p>Baseline demographics of real-life data from 227 patients.</p

Costs and resource use.

<p>Costs and resource use.</p

Cost-effectiveness plane.

<p>WTP: Willingness to pay: linear threshold corresponds to the WTP value used by NICE in making reimbursement decisions (£30.000 per QALY gained). Each quadrant corresponds to one incremental cost option (cost saving, not cost saving) and one incremental benefit option (more/less benefit than comparator therapy).</p

Health State Utility Values (HSUV).

<p>Health State Utility Values (HSUV).</p

Overview of transition probabilities applied in the model.

<p>Overview of transition probabilities applied in the model.</p