Royal London Hospital

About: Royal London Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 4854 authors who have published 5081 publications receiving 168207 citations. The organization is also known as: London Infirmary & London Hospital.

Cost-Effectiveness Analyses of Natalizumab (Tysabri®) Compared with Other Disease-Modifying Therapies for People with Highly Active Relapsing-Remitting Multiple Sclerosis in the UK

Abstract: Natalizumab (Tysabri®) is a new disease-modifying therapy that has been shown to be clinically effective in patients with relapsing-remitting multiple sclerosis (RRMS) and has been licensed for use in patients with highly active RRMS (HARRMS). These patients are those who experience higher relapse rates and faster disability progression than the general RRMS population. To estimate the cost effectiveness of natalizumab compared with interferon-s, glatiramer acetate and best supportive care from various UK cost perspectives. A 30-year Markov model was developed, based on previously published models for multiple sclerosis, to estimate transition between disability states and the probability of relapse within disability states. The model was parameterized with data from the UK Multiple Sclerosis (MS) Survey 2005 and data from the AFFIRM study, a 2-year multicentre, randomized, double-blind, placebo-controlled trial of natalizumab in RRMS patients. Additional data were sourced from the literature. A UK societal cost perspective was used in the base case, with additional cost perspectives considered in the sensitivity analysis. The baseline characteristics for the patient group were taken from the patient population in the AFFIRM study (mean age 36 years, mean time since diagnosis 5 years and a mean Kurtzke Extended Disability Status Scale [EDSS] score of 2.5). The model and its parameterization were designed and developed to support a reimbursement application for natalizumab submitted to the UK National Institute for Health and Clinical Excellence (NICE). Efficacies for natalizumab and glatiramer acetate were taken from clinical trial data, and for interferon-s from a meta-analysis of clinical trial data. Disutilities from adverse events for each comparator were also included in the model. Outcomes and costs were discounted at 3.5% per anum. Costs for interferon-s and glatiramer acetate were based on published prices (year 2006 values) under the UK Risk Sharing Scheme, and for natalizumab the UK NHS list price was used. Diagnostic, administration and adverse event costs were also included. The incremental cost-effectiveness ratios (ICERs) were calculated for the base case, and a probabilistic sensitivity analysis was performed to assess the probability of cost effectiveness at different willingness-to-pay thresholds. The ICER for natalizumab compared with interferon-s was £2300 per QALY. Compared with glatiramer acetate, it was £2000 per QALY, and compared with best supportive care it was £8200 per QALY. From a health and social care cost perspective, the ICERs were £18 700, £20 400 and £25 500 per QALY, respectively. At a willingness-to-pay threshold of £30 000 per QALY, the probability of natalizumab being cost effective against any comparator from a societal perspective was >89%. If UK society is willing to pay more than £8200 per QALY, or Health and Social Services are willing to pay more than £26 000 per QALY, this analysis suggests that natalizumab is likely to be a cost-effective treatment for all patients with HARRMS.

Anterior abdominal wall reconstruction with a Permacol implant.

Abstract: Laparostomy wound management is a difficult problem especially with a stoma and the potential risk of infection. A case describing the use of a permanent porcine dermal collagen implant in the repair of a massive ventral hernia, in a patient with a large post-laparostomy defect and colostomy is outlined. The implant was not rejected, and after 12 months, there was no evidence of residual or recurrent hernia. The search for the ultimate biomaterial for reconstructing abdominal wall defects is ongoing. Collagen based implants appear to have many of the requirements that an ideal material should possess.

The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas

Abstract: Using digoxigenin-labelled, synthetic oligonucleotide probe cocktails of angiogenin and bFGF genes, the expression of the two genes was observed by in situ hybridization in ten colonic adenocarcinomas, seven gastric adenocarcinomas, and four hepatocellular carcinomas. The angiogenin gene was expressed in eight of the ten cases of colonic adenocarcinoma and in all of the four cases where dysplastic glands were found. Angiogenin expression was evident in four of the seven cases of gastric adenocarcinoma. bFGF expression was detected in only five of the seven gastric carcinoma cases. The mRNAs for angiogenin and bFGF were mainly cytoplasmic in distribution and were only occasionally seen in the nuclei of the positive cells. Neither the angiogenin gene mRNA nor the bFGF mRNA was expressed in the four cases of hepatocellular carcinoma. It is postulated that the angiogenin gene may play an important role in angiogenesis in colonic adenocarcinomas; in gastric cancers, both angiogenin and bFGF were involved in this process. For hepatocellular carcinomas, neither angiogenin nor bFGF production appeared to be related to angiogenesis.

Evolutionary history of human colitis-associated colorectal cancer

Abstract: Objective IBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing. Design Exome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC. Results 10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated ‘catastrophic’ CNA increase. Conclusions Evolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.

Rectal intussusception in symptomatic patients is different from that in asymptomatic volunteers

Abstract: Background: Rectal intussusception is a common finding at evacuation proctography in both symptomatic and asymptomatic individuals. Little information exists, however, as to whether intussusception morphology differs between patients with evacuatory dysfunction and healthy volunteers. Methods: Thirty patients (19 women; median age 44 (range 21–76) years) with disordered rectal evacuation, in whom an isolated intussusception was seen on proctography, were studied. Various morphological parameters were measured, and compared with those from 11 asymptomatic controls (six women; median age 30 (range 24–38) years) found, from 31 volunteers, to have rectal intussusception. Intussusceptum thickness greater than 3 mm was designated as full thickness. Intussuscepta impeding evacuation were deemed to be occluding. Results: Twenty-two patients had full-thickness intussusception, compared with two controls (P = 0·003). Intussusceptum thickness was significantly greater in the symptomatic group (anterior component: P = 0·004; posterior: P = 0·011). Twenty patients in the symptomatic group, but only three subjects in the control group, had a mechanically occluding intussusception (P = 0·043), although only three patients demonstrated evacuatory dynamics outside the normal range. Conclusion: Rectal intussusception in patients with evacuatory dysfunction is more advanced morphologically than that seen in asymptomatic controls; it is predominantly full thickness in patients and mucosal in controls. However, caution is required when selecting patients for intervention based solely on radiological findings. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.