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.

Does ethnic origin influence the incidence or severity of keratoconus

Abstract: Purpose Keratoconus affects all races, yet very little infonnation exists as to the relative frequency in patients of different ethnic origin. We aimed to establish the incidence and severity of keratoconus in Asian and white patients. Methods The hospital records of the ophthalmology department of a large Midlands hospital with a catchment population of approximately 900 000 (87% white, 11% Asian, 2% other) were examined retrospectively for the 10 year period from 1989 to 1998. Results For the age group 10-44 years the prevalence of keratoconus in Asians and whites was 229 and 57 per 100 000 respectively, a relative prevalence of 4 to 1. The incidence of keratoconus in the same age group was 19.6 and 4.5 per 100 000 per year respectively, a relative incidence of 4.4 to 1. Asians were significantly younger at presentation compared with whites (mean 22.3 ± 6.5 vs 26.5 ± 8.5 years, p < 0.0001). A first corneal graft was carried out on 14% of the Asian and 15% of the white patients. Of those having grafts, Asians were significantly younger than white patients at the time of diagnosis (mean 19.1 ± 4.8 vs 25.7 ± 7.3 years, p=0.005) and at operation (mean 21.4 ± 5.0 vs 28.7 ± 7.7 years, p=0.004). The interval from diagnosis to operation, though shorter for Asians, was not significantly different (mean 1.8 ± 1.4 vs 2.5 ± 1.7 years, p=0.2). Conclusion The results show previously unrecognised racial differences in the hospital presentation of keratoconus in the UK. Compared with white patients, Asians have a fourfold increase in incidence, are younger at presentation and require corneal grafting at an earlier age.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus

Abstract: BackgroundThe 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. MethodsWe studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. ResultsThe stimulated C-peptide level dec...

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

Abstract: Summary Background Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder. Methods This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3–pT4 disease or node positive (pN1–3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. Findings From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7·0 years (IQR 5·2–8·7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0·78, 95% CI 0·56–1·08; p=0·13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0·54, 95% CI 0·4–0·73, p Interpretation Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. Funding Lilly, Canadian Cancer Society Research.

The science of nebulised drug delivery

Abstract: Effective nebuliser therapy requires a device distinguished from a simple atomiser by the incorporation of baffles which selectively rethat repeatedly and quickly delivers sufficient drug to the site of action, with minimal wastage, move large droplets from the outgoing spray. Early models were essentially atomisers conat a low cost. Clinicians are bombarded with competing claims about different nebuliser sysstructed of glass and operated manually by compressing a hand bulb attached to the air tems. In many cases, however, insufficient details are available to make the most appropriate inlet tube. In 1946 pumps providing a continuous flow of air were advocated and the choice. The rapid increase in the number of nebulisers marketed and significant differences Collinson nebuliser, constructed of ebonite with a plate baffle to filter out particles larger in design may result in drug delivery to patients varying by a factor of two or more. than 5 lm, became the most popular nebuliser in this country. In 1958 Wright described a new nebuliser, considerably more compact than the Collinson, with a moulded perspex top. Drug delivery from nebulisers Most of the prescribed medication for nebuNow discontinued, it found widespread use in bronchial challenge testing. 14 lisers never reaches the lungs. Of the dose placed in the nebuliser chamber, perhaps two With the advent of portable, oil free compressors and injection moulding of plastics, a thirds remains there at the end of nebulisation. Two thirds of the dose released from the nebuwide variety of disposable nebulisers has become available. Recent advances in their liser may be released during expiration and passes into the surrounding air. Some of the design have considerably altered the amount of drug patients receive. inhaled drug will be in particles too large to reach the lung, and some in particles so small that they do not deposit but are simply exhaled again. With many nebulisers only 10% of the    In a jet nebuliser the driving gas passes through prescribed dose may reach the lung. For bronchodilators, where a small dose may a very narrow hole, known as a Venturi, from a high pressure system (fig 1). At the Venturi achieve an adequate result, this may not matter. It is more important for drugs with dose related the pressure falls and the gas velocity increases greatly producing a cone shaped front. This effects (and side effects) such as steroids, and for expensive medications such as rhDNase. passes at high velocity over the end of a narrow liquid feed tube or concentric feeding system creating a negative pressure at this point. As a result of this fall in pressure, liquid is sucked Nebuliser types: how they work Nebulisers used in aerosol drug delivery proup by the Bernoulli effect (see Appendix 1) and is drawn out into fine ligaments. The duce a polydisperse aerosol where most of the drug released is contained in particles 1–5 lm ligaments then collapse into droplets under the influence of surface tension. This primary in diameter. Most nebulisers use compressed air for atomisation (fig 1), but some use ultrageneration (atomisation) typically produces droplets 15–500 lm in diameter. Coarse sonic energy (fig 2). A nebuliser may be