Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability.

Abstract: Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens Information on the acceptability of prolonged administration of daily curcumin is not available This is of vital importance to implement chemoprevention strategies This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin Curcumin C3 complex (235 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection Safety and tolerance were monitored Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS) Twenty-four of 26 patients commencing curcumin completed the course Six patients reported mild gastrointestinal adverse events Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants Mean tissue levels were 484 μg/g (1278 nmol/g) of parent curcuminoids The major conjugate, curcumin glucuronide, was detectable in 29 of 35 biopsies High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa The regimen used here seems safe, and patients support its use in long-term trials

Marimastat: the clinical development of a matrix metalloproteinase inhibitor.

Abstract: Marimastat (BB-2516) is the first orally bioavailable matrix metalloproteinase inhibitor to have entered clinical trials in the field of oncology. It has excellent bioavailability and has completed Phase I, II and some Phase III trials. In Phase I studies, which recruited patients with various malignancies, the main toxicity observed was mild to severe joint and muscle pain seen in > 60% of patients receiving a dose of marimastat > 50 mg b.i.d. The symptoms were reversible on discontinuation of the drug and their incidence has been reduced by using marimastat 10 mg b.i.d. In a number of Phase II studies in a variety of tumours, serum tumour markers were used as surrogate determinants of efficacy. Results were interpreted as indicating activity, but this has not yet translated into improved survival in the Phase III studies, which have been completed in pancreatic or gastric carcinoma and glioma. It is likely that these drugs will be most effective in the setting of minimal tumour volume such as in adjuvant treatment or maintenance therapy following response to standard cytotoxics. Therefore, the analysis of Phase III studies in small cell lung cancer (SCLC) where this hypothesis has been tested is awaited with interest. Marimastat can be safely co-administered with conventional cytotoxics and radiotherapy and Phase III studies using these approaches are currently ongoing.

A year's trauma admissions and the effect of the weather.

Abstract: Purpose of the study : To study the admissions to a busy trauma unit on a day-by-day basis over a 1 year period, and to look for any correlation with local weather variation or temporal factors (day of the week, weekends/school holidays, etc.). Method : Admissions data for the Trauma Unit at the Leicester Royal Infirmary was collected from an administrative database and ward records for the calendar year of 1998. Admissions were split into four groups: all admissions, adult admissions, admissions for proximal femoral fractures (neck of femur (NOF)) and paediatric admissions. Weather information for the local area was obtained from the Meteorological Office. Details of school holidays were obtained from the local Education Department. The above variables were examined using Poisson regression analysis for their potential importance in explaining day-to-day variation in admission rates for the four groups. Results : For adult and NOF admissions, none of the weather factors appeared to explain variation in incidence, only day of the week appears to be important, with the earlier part of the week yielding a highly statistically significant increase in the relative incidence of trauma admissions. For both paediatric and total admissions, a number of factors appear important, including maximum and minimum temperatures, hours of sunshine, day of the week and month of the year. Daily rainfall, significant weather and whether the day was a school day or school holiday did not appear to be important on univariate analysis. Conclusion : Trauma admissions are related to both weather and temporal factors. This may have implications both in terms of prevention and in planning of care provision in trauma units.

Cost-effectiveness of neonatal extracorporeal membrane oxygenation based on 7-year results from the United Kingdom Collaborative ECMO Trial.

Abstract: OBJECTIVE. To assess the long-term cost-effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure. METHODS. A prospective economic evaluation was conducted alongside a pragmatic randomized, controlled trial in which 185 infants were randomly allocated to ECMO (n = 93) or conventional management (n = 92) and then followed up to 7 years of age. Information about their use of health services during the follow-up period was combined with unit costs (£, 2002–2003 prices) to obtain a net cost per child. The cost-effectiveness of neonatal ECMO was expressed in terms of incremental cost per additional life year gained and incremental cost per additional disability-free life year gained. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics at alternative willingness-to-pay thresholds held by decision-makers for an additional life year and for an additional disability-free life year. RESULTS. Over 7 years, neonatal ECMO was effective at reducing known death or severe disability. Mean health service costs during the first 7 years of life were £30270 in the ECMO group and £10229 in the conventional management group, generating a mean cost difference of £20041 that was statistically significant. The incremental cost per life year gained was estimated at £13385. The incremental cost per disability-free life year gained was estimated at £23566. At the notional willingness-to-pay threshold of £30000 for an additional life year, the probability that neonatal ECMO is cost-effective at 7 years was estimated at 0.98. This translated into a mean net benefit of £24362 for each adoption of neonatal ECMO rather than conventional management. CONCLUSIONS. This study provides rigorous evidence of the cost-effectiveness of neonatal ECMO during childhood.