St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

Acute pain management for opioid dependent patients

Abstract: Patients requiring acute pain management may be opioid dependent as a result of either recreational or therapeutic opioid use, including those in opioid addiction programmes. Pain in these patients is often under-estimated and under-treated. In addiction, drug-seeking behaviour differentiates it from simple dependence. With few randomised controlled trials, current evidence predominantly consists of guidelines based on case reports, retrospective studies and expert opinion. Consensus recommendations include maintaining regular provision of the patient's pre-existing opioid requirement, with additional analgesia, ideally multimodal, in appropriate combinations of short-acting opioid (as required), local anaesthesia, and adjuvant anti-inflammatory analgesics and paracetamol. Patient controlled analgesia with higher bolus doses and shorter lock-out intervals is a recommended strategy. Transdermal opioid patches and implantable pumps will continue to deliver opioid, to which non-opioid and short-acting opioids may be added. Re-exposure to opioid is ideally avoided in previously addicted patients, but if not feasible, opioid therapy should be prescribed.

The concentration of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in human umbilical cord serum at delivery: relation to fetal weight.

Abstract: Serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) have been determined by radioimmunoassay in the maternal circulation (n = 91) and in the umbilical artery (n = 56) and vein (n = 90) of man. In both the umbilical artery and vein, the concentration of serum IGF-I showed an inverse correlation with birthweight (P less than 0.005 and P less than 0.001 respectively); the mean serum IGF-I levels in the small-for-gestational-age (SGA) group were significantly higher than those in average-for-gestational-age (AGA) neonates (P less than 0.01 and P less than 0.001 respectively). However, maternal serum IGF-I showed no association with birthweight and there was no significant difference between the SGA and AGA groups. These observations imply that the production of IGF-I in the maternal and fetal compartments is independent and that there is unlikely to be transfer of IGF-I across the placenta. Serum IGFBP-1 levels in both maternal and umbilical cord blood (artery and vein) showed an inverse relation to birthweight (P less than 0.001, P less than 0.005 and P less than 0.001 respectively). Increased IGFBP-1 levels in the umbilical artery and vein were observed in the SGA group. These findings suggest that IGFBP-1 might inhibit the action of IGF-I in both the maternal and the fetal compartments and that the rise in IGFBP-1 could be a primary factor in retardation of fetal growth. Alternatively, circulating IGF-I and IGFBP-1 levels may only be a secondary reflection of local tissue events involved in fetal growth.

Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial.

Abstract: Importance Preclinical studies show that arginine deprivation is synthetically lethal in argininosuccinate synthetase 1 (ASS1)-negative cancers, including mesothelioma. The role of the arginine-lowering agent pegylated arginine deiminase (ADI-PEG20) has not been evaluated in a randomized and biomarker-driven study among patients with cancer. Objective To assess the clinical impact of arginine depletion in patients with ASS1-deficient malignant pleural mesothelioma. Design, Setting, and Participants A multicenter phase 2 randomized clinical trial, the Arginine Deiminase and Mesothelioma (ADAM) study, was conducted between March 2, 2011, and May 21, 2013, at 8 academic cancer centers. Immunohistochemical screening of 201 patients (2011-2013) identified 68 with advanced ASS1-deficient malignant pleural mesothelioma. Interventions Randomization 2:1 to arginine deprivation (ADI-PEG20, 36.8 mg/m 2 , weekly intramuscular) plus best supportive care (BSC) or BSC alone. Main Outcomes and Measures The primary end point was progression-free survival (PFS) assessed by modified Response Evaluation Criteria in Solid Tumors (RECIST) (target hazard ratio, 0.60). Secondary end points were overall survival (OS), tumor response rate, safety, and quality of life, analyzed by intention to treat. We measured plasma arginine and citrulline levels, anti–ADI-PEG20 antibody titer, ASS1 methylation status, and metabolic response by 18 F-fluorodeoxyglucose positron-emission tomography. Results Median (range) follow-up in 68 adults (median [range] age, 66 [48-83] years; 19% female) was 38 (2.5-39) months. The PFS hazard ratio was 0.56 (95% CI, 0.33-0.96), with a median of 3.2 months in the ADI-PEG20 group vs 2.0 months in the BSC group ( P = .03) (absolute risk, 18% vs 0% at 6 months). Best response at 4 months (modified RECIST) was stable disease: 12 of 23 (52%) in the ADI-PEG20 group vs 2 of 9 (22%) in the BSC group ( P = .23). The OS curves crossed, so life expectancy was used: 15.7 months in the ADI-PEG20 group vs 12.1 months in the BSC group (difference of 3.6 [95% CI, −1.0 to 8.1] months; P = .13). The incidence of symptomatic adverse events of grade at least 3 was 11 of 44 (25%) in the ADI-PEG20 group vs 4 of 24 (17%) in the BSC group ( P = .43), the most common being immune related, nonfebrile neutropenia, gastrointestinal events, and fatigue. Differential ASS1 gene-body methylation correlated with ASS1 immunohistochemistry, and longer arginine deprivation correlated with improved PFS. Conclusions and Relevance In this trial, arginine deprivation with ADI-PEG20 improved PFS in patients with ASS1-deficient mesothelioma. Targeting arginine is safe and warrants further clinical investigation in arginine-dependent cancers. Trial Registration clinicaltrials.gov Identifier:NCT01279967

CT assessment of tumour response to treatment: comparison of linear, cross-sectional and volumetric measures of tumour size.

Abstract: Changes in cross-sectional area are currently used to assess tumour response to treatment. The aims of this study were to validate a helical CT technique for volume determination using a series of phantoms and to compare tumour responses indicated by one-, two- and three-dimensional measures of tumour size change in patients treated for germ cell cancer or lymphoma. All studies were performed on an IGE HiSpeed Advantage helical CT scanner with an Advantage Windows workstation. Phantom volumes were calculated using volume reconstruction software and compared with reference volumes determined by water displacement. 20 lymph node masses were studied on serial CT scans in 16 patients treated with chemotherapy for germ cell cancer or lymphoma. For each lesion the maximum diameter, maximum cross-sectional area and volume were determined before and after treatment. Tumour response was assessed using the standard World Health Organisation criteria (i.e. changes in cross-sectional area) and the newly proposed unidimensional response evaluation criteria in solid tumour (RECIST). The CT volume measurement error was 1.0-5.1% for regularly shaped phantoms larger than 35 cm3. In the assessment of treatment response there was 90% agreement between one-dimensional (1D) and two-dimensional (2D) measurements and 100% agreement between 2D and three-dimensional (3D) measurements. CT volume measurements are accurate and reproducible, particularly for larger structures. Assessment of tumour response using 1D, 2D and 3D measures had limited influence on the classification of treatment response. However, the impact of CT assessment of tumour response using 1D, 2D and 3D measurements on clinical decisions and patient outcome remains to be determined.