A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study)

Contains fulltext : 87553.pdf (publisher's version ) (Open Access)BACKGROUND: The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? METHOD/DESIGN: The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3 x 40 = 120 patients is calculated. DISCUSSION: The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. TRIAL REGISTRATION: ISRCTN44649165

The quality of research synthesis in surgery: the case of laparoscopic surgery for colorectal cancer

Peer reviewedPublisher PD

The P2Y1 receptor is involved in the maintenance of glucose homeostasis and in insulin secretion in mice

Pancreatic β cells express several P2 receptors including P2Y1 and the modulation of insulin secretion by extracellular nucleotides has suggested that these receptors may contribute to the regulation of glucose homeostasis. To determine whether the P2Y1 receptor is involved in this process, we performed studies in P2Y1 mice. In baseline conditions, P2Y1-mice exhibited a 15% increase in glycemia and a 40% increase in insulinemia, associated with a 10% increase in body weight, pointing to a role of the P2Y1 receptor in the control of glucose metabolism. Dynamic experiments further showed that P2Y1-mice exhibited a tendency to glucose intolerance. These features were associated with a decrease in the plasma levels of free fatty acid and triglycerides. When fed a lipids and sucrose enriched diet for 15 weeks, the two genotypes no longer displayed any significant differences. To determine whether the P2Y1 receptor was directly involved in the control of insulin secretion, experiments were carried out in isolated Langerhans islets. In the presence of high concentrations of glucose, insulin secretion was significantly greater in islets from P2Y1-mice. Altogether, these results show that the P2Y1 receptor plays a physiological role in the maintenance of glucose homeostasis at least in part by regulating insulin secretion

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma

<p>Abstract</p> <p>Background</p> <p>Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use.</p> <p>Methods</p> <p>A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms.</p> <p>Results</p> <p>The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); <it>P </it>< 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (<it>P </it>< 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms.</p> <p>Conclusions</p> <p>GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms.</p

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease

Iterative Structure-Based Peptide-Like Inhibitor Design against the Botulinum Neurotoxin Serotype A

The botulinum neurotoxin serotype A light chain (BoNT/A LC) protease is the catalytic component responsible for the neuroparalysis that is characteristic of the disease state botulism. Three related peptide-like molecules (PLMs) were designed using previous information from co-crystal structures, synthesized, and assayed for in vitro inhibition against BoNT/A LC. Our results indicate these PLMS are competitive inhibitors of the BoNT/A LC protease and their Ki values are in the nM-range. A co-crystal structure for one of these inhibitors was determined and reveals that the PLM, in accord with the goals of our design strategy, simultaneously involves both ionic interactions via its P1 residue and hydrophobic contacts by means of an aromatic group in the P2′ position. The PLM adopts a helical conformation similar to previously determined co-crystal structures of PLMs, although there are also major differences to these other structures such as contacts with specific BoNT/A LC residues. Our structure further demonstrates the remarkable plasticity of the substrate binding cleft of the BoNT/A LC protease and provides a paradigm for iterative structure-based design and development of BoNT/A LC inhibitors

Splash!: a prospective birth cohort study of the impact of environmental, social and family-level influences on child oral health and obesity related risk factors and outcomes

Background: Dental caries (decay) is the most prevalent disease of childhood. It is often left untreated and can impact negatively on general health, and physical, developmental, social and learning outcomes. Similar to other health issues, the greatest burden of dental caries is seen in those of low socio-economic position. In addition, a number of diet-related risk factors for dental caries are shared risk factors for the development of childhood obesity. These include high and frequent consumption of refined carbohydrates (predominately sugars), and soft drinks and other sweetened beverages, and low intake of (fluoridated) water. The prevalence of childhood obesity is also at a concerning level in most countries and there is an opportunity to determine interventions for addressing both of these largely preventable conditions through sustainable and equitable solutions. This study aims to prospectively examine the impact of drink choices on child obesity risk and oral health status.Methods/Design: This is a two-stage study using a mixed methods research approach. The first stage involves qualitative interviews of a sub-sample of recruited parents to develop an understanding of the processes involved in drink choice, and inform the development of the Discrete Choice Experiment analysis and the measurement instruments to be used in the second stage. The second stage involves the establishment of a prospective birth cohort of 500 children from disadvantaged communities in rural and regional Victoria, Australia (with and without water fluoridation). This longitudinal design allows measurement of changes in the child&rsquo;s diet over time, exposure to fluoride sources including water, dental caries progression, and the risk of childhood obesity.Discussion: This research will provide a unique contribution to integrated health, education and social policy and program directions, by providing clearer policy relevant evidence on strategies to counter social and environmental factors which predispose infants and children to poor health, wellbeing and social outcomes; and evidence-based strategies to promote health and prevent disease through the adoption of healthier lifestyles and diet. Further, given the absence of evidence on the processes and effectiveness of contemporary policy implementation, such as community water fluoridation in rural and regional communities it&rsquo;s approach and findings will be extremelyinformative.<br /