St Thomas' Hospital

About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype

Abstract: Background The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood.

Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial

Abstract: Summary Background Enzalutamide significantly increased overall survival and radiographic progression-free survival compared with placebo in the PREVAIL trial of asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer. We report the effect of enzalutamide on health-related quality of life (HRQoL), pain, and skeletal-related events observed during this trial. Methods In this phase 3, double-blind trial, patients were randomly assigned (1:1) to receive enzalutamide 160 mg/day (n=872) or placebo (n=845) orally. HRQoL was assessed at baseline and during treatment using the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and EQ-5D questionnaires. Pain status was assessed at screening, baseline, week 13, and week 25 with the Brief Pain Inventory Short Form (BPI-SF). The primary analysis of HRQoL data used a mixed-effects model to test the difference between least square means change from baseline at week 61. We assessed change from baseline, percentage improvement, and time to deterioration in HRQoL and pain, the proportion of patients with a skeletal-related event, and time to first skeletal-related event. Analysis was done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01212991. Findings Median treatment duration was 16·6 months (IQR 10·1–21·1) in the enzalutamide group and 4·6 months (2·8–9·7) in the placebo group. The mixed-effects model analyses showed significant treatment differences in change from baseline to week 61 with enzalutamide compared with placebo for most FACT-P endpoints and EQ-5D visual analogue scale. Median time to deterioration in FACT-P total score was 11·3 months (95% CI 11·1–13·9) in the enzalutamide group and 5·6 months (5·5–5·6) in the placebo groups (hazard ratio [HR] 0·62 [95% CI 0·54–0·72]; p vs 181 [23%] of 790), in EQ-5D utility index (224 [28%] of 812 vs 99 [16%] of 623), and visual analogue scale (218 [27%] of 803 vs 106 of [18%] 603; all p vs 257 [42%] of 610; p vs 135 [38%] of 360; p=0·068). 278 (32%) of 872 patients in the enzalutamide group and 309 (37%) of 845 patients in the placebo group had experienced a skeletal-related event by data cutoff. Median time to first skeletal-related events in the enzalutamide group was 31·1 months (95% CI 29·5–not reached) and 31·3 months (95% CI 23·9–not reached) in the placebo group (HR 0·72 [95% CI 0·61–0·84]; p Interpretation In addition to improving overall survival relative to placebo, enzalutamide significantly improves patient-related outcomes and delays occurrence of first skeletal-related event in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Funding Astellas Pharma and Medivation.

The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: the Chingford Study.

Abstract: Objective Investigators performing cross-sectional studies have reported small increases in bone mineral density (BMD) in subjects with osteoarthritis (OA). This study was undertaken to examine the association of bone mass with incident and progressive disease and to determine whether prior fractures influence the development of OA. Methods Eight hundred thirty women had repeat knee radiographs 48 months from baseline. All radiographs were graded on the presence or absence of osteophytes and joint space narrowing (JSN). Incident knee OA was defined as new disease in the 715 women without knee OA at baseline. Progression was a change of at least one grade in the 115 women with baseline knee OA. All women underwent bone densitometry of the lumbar spine and hip. Rates of subsequent incident OA were compared between fracture groups. Results The 95 women with incident knee osteophytes had significantly higher baseline spine BMD (1.01 gm/cm2versus 0.95 gm/cm2, or 6.3%; P = 0.002) and significantly higher hip BMD (0.79 gm/cm2 versus 0.76 gm/cm2, or 3.9%; P = 0.02) than those without incident disease. For the 33 women whose osteophytes progressed, no difference was seen compared with nonprogressors in spine BMD, but hip BMD was modestly reduced (−2.5%). The 81 women who had incident JSN had nonsignificantly higher baseline spine BMD (3.0%), while no difference was seen for the 30 women whose JSN had progressed. For hip BMD, a nonsignificant increase was seen in those with incident JSN (1.3%), and a nonsignificant reduction was seen in those whose JSN progressed (−2.7%). One hundred forty-five women sustained peripheral fractures, mainly in the distal forearm (27.6%) and vertebrae (28.3%). Women with a peripheral fracture had a reduced risk of subsequently developing incident knee OA (odds ratio [OR] 0.30, 95% confidence interval [95% CI] 0.11–0.84). Although numbers were smaller, nonsignificant reductions in rates of incident OA were seen for those with distal forearm (OR 0.40, 95% CI 0.11–1.49) and vertebral (OR 0.20, 95% CI 0.07–1.61) fractures. Conclusion These results confirm that for women who develop incident knee OA, defined by osteophytes, BMD is higher and of a magnitude similar to that shown in cross-sectional studies. Low BMD at the hip appears weakly related to progression. Women with previous fractures have less chance of developing OA, independent of BMD status. Although the mechanism for this action is unclear, these results suggest a possible common role of bone turnover and repair in the early manifestations of OA.

Time-kill studies of tea tree oils on clinical isolates

Abstract: Tea tree oil has recently emerged as an effective topical antimicrobial agent active against a wide range of organisms. Tea tree oil may have a clinical application in both the hospital and community, especially for clearance of methicillin-resistant Staphylococcus aureus (MRSA) carriage or as a hand disinfectant to prevent cross-infection with Gram-positive and Gramnegative epidemic organisms. Our study, based on the time-kill approach, determined the kill rate of tea tree oil against several multidrug-resistant organisms, including MRSA, glycopeptide-resistant enterococci, aminoglycoside-resistant klebsiellae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, and also against sensitive microorganisms. The study was performed with two chemically different tea tree oils. One was a standard oil and the other was Clone 88 extracted from a specially bred tree, which has been selected and bred for increased activity and decreased skin irritation. Our results confirm that the cloned oil had increased antimicrobial activity when compared with the standard oil. Most results indicated that the susceptibility pattern and Gram reaction of the organism did not influence the kill rate. A rapid killing time (less than 60 min) was achieved with both tea tree oils with most isolates, but MRSA was killed more slowly than other organisms.

A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa.

Abstract: The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype.