Showing papers by "Leicester Royal Infirmary published in 2009"
TL;DR: Results from this randomised trial provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer.
1,296 citations
TL;DR: A meta-analysis of 118 studies that assessed the accuracy of unassisted diagnoses of depression by GPs suggests that misidentifications outnumber missed cases and diagnosis could be improved by re-assessment of individuals who might have depression.
1,017 citations
TL;DR: In rectal cancer, the plane of surgery achieved is an important prognostic factor for local recurrence, and both a negative circumferential resection margin and a superior plane of Surgery achieved were associated with lowLocal recurrence rates.
897 citations
TL;DR: The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment ofcarotid disease and the benefit from CEA in asymptomatic women is significantly less than in men.
522 citations
TL;DR: Investigation of the effect of knockdown or mutations of RSPH9 orthologs in zebrafish and Chlamydomonas indicate that radial spoke head proteins are important in maintaining normal movement in motile, "9+2"-structure cilia and flagella.
Abstract: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous inherited disorder arising from dysmotility of motile cilia and sperm. This is associated with a variety of ultrastructural defects of the cilia and sperm axoneme that affect movement, leading to clinical consequences on respiratory-tract mucociliary clearance and lung function, fertility, and left-right body-axis determination. We performed whole-genome SNP-based linkage analysis in seven consanguineous families with PCD and central-microtubular-pair abnormalities. This identified two loci, in two families with intermittent absence of the central-pair structure (chromosome 6p21.1, Zmax 6.7) and in five families with complete absence of the central pair (chromosome 6q22.1, Zmax 7.0). Mutations were subsequently identified in two positional candidate genes, RSPH9 on chromosome 6p21.1 and RSPH4A on chromosome 6q22.1. Haplotype analysis identified a common ancestral founder effect RSPH4A mutation present in UK-Pakistani pedigrees. Both RSPH9 and RSPH4A encode protein components of the axonemal radial spoke head. In situ hybridization of murine Rsph9 shows gene expression restricted to regions containing motile cilia. Investigation of the effect of knockdown or mutations of RSPH9 orthologs in zebrafish and Chlamydomonas indicate that radial spoke head proteins are important in maintaining normal movement in motile, "9+2"-structure cilia and flagella. This effect is rescued by reintroduction of gene expression for restoration of a normal beat pattern in zebrafish. Disturbance in function of these genes was not associated with defects in left-right axis determination in humans or zebrafish.
305 citations
TL;DR: A new definition of partial remission in type 1 diabetes that reflects residual β-cell function and has better stability compared with the conventional definitions is proposed, including both glycemic control and insulin dose.
Abstract: OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged 300 pmol/l was used to define partial remission. The IDAA1C 300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.
234 citations
TL;DR: In this paper, the long-term prognostic value of growth differentiation factor-15 (GDF-15) in patients post-acute myocardial infarction (AMI) was assessed.
Abstract: Aims Our aim was to assess the long-term prognostic value of growth differentiation factor-15 (GDF-15) in patients post-acute myocardial infarction (AMI). Growth differentiation factor-15 is a member of the transforming growth factor β family. Growth differentiation factor-15 is expressed in the myocardium and upregulated due to ‘stress’ and has been shown to have antiapoptotic actions. Its role in the cardiovascular system however is not well defined. We were interested to see if GDF-15 could provide long-term prognostic value in post-AMI patients. We compared GDF-15 with N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Methods and results We recruited 1142 consecutive post-AMI patients [820 men, median (range) age 67 (24–97) years] in a prospective study with a follow-up period of 505 (range 1–2837) days. Growth differentiation factor-15 levels increased with increasing Killip class ( P < 0.001) and were correlated with NT-proBNP ( r = 0.47, P < 0.001). Using a multivariable Cox proportional hazards model, log GDF-15 (HR 1.77), log NT-proBNP (HR 2.06), age (HR 1.03) Killip class above 1, (HR 1.62), use of beta-blockers (HR 0.54) and past history of MI (HR 1.44) were significant independent predictors of death or heart failure (HF). Predictors of death were log NT-proBNP, log GDF-15, age, eGFR, past history of MI, use of beta-blockers, and use of ACE inhibitors or angiotensin receptor blockers. The C-statistic for GDF-15 for predicting death or HF at 1 year was 0.73 (95% CI: 0.70–0.76, P < 0.001) and was 0.76 (95% CI: 0.70–0.80, P < 0.001) for NT-proBNP. Combining these markers yielded an AUC of 0.81 (95% CI: 0.77–0.85), which exceeded that of GDF-15 ( P < 0.001) and NT-proBNP ( P = 0.004) alone. The Kaplan–Meier analysis revealed that those patients with above median GDF-15 and NT-proBNP had the highest event rate for death and HF (log rank 50.22, P < 0.001).
Conclusion Growth differentiation factor-15 is a new marker for predicting death and HF in post-AMI patients. GDF-15 provides prognostic information over and above clinical factors and the established biomarker NT-proBNP. Combined levels of GDF-15 with NT-proBNP can identify a high-risk group of patients.
193 citations
TL;DR: Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.
Abstract: Background Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen. Methods We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005-2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads. Results Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1-12 years (median age, 3 years, 1 month) were enrolled. By days 4-7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8-12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir (P = .004). There was no evidence of prolonged illness in children infected with drug-resistant virus. Conclusions Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.
185 citations
TL;DR: Recommendations for the reporting of ultrasound investigations of the extra cranial arteries are presented, based on the NASCET method of grading carotid bulb disease, produced by a Joint Working Group formed between the Vascular Society of Great Britain and Ireland and the Society for Vascular Technology.
181 citations
TL;DR: The findings suggest that nystagmus is more common in the general population than previously thought and may be of significance in resource allocation and health care planning.
Abstract: PURPOSE Nystagmus, which can be infantile (congenital) or acquired, affects all ages. The prevalence of nystagmus in the general population is unknown. New genetic research and therapeutic modalities are emerging. Previous estimates have been based on wider ophthalmic epidemiologic studies within specific occupational or age groups. The authors carried out the first epidemiologic study to specifically establish the prevalence of nystagmus in Leicestershire and Rutland in the United Kingdom. METHODS Three independent data sources identified persons with nystagmus from the hospital and community. The first was a hospital-based questionnaire and clinical survey (n = 238). The visually impaired services (n = 414) and education services (n = 193) in Leicestershire provided the second and third separately obtained community-based sources of information. Capture-recapture statistical analysis was used to estimate prevalence. RESULTS The prevalence of nystagmus in the general population was estimated to be 24.0 per 10,000 population (95% confidence interval [CI], +/-5.3). The most common forms of nystagmus were neurologic nystagmus (6.8 per 10,000 population; 95% CI, +/-4.6), nystagmus associated with low vision such as congenital cataracts (4.2 per 10,000; 95% CI, +/-1.2), and nystagmus associated with retinal diseases such as achromatopsia (3.4 per 10,000 population; 95% CI, +/-2.1). Within ethnic groups, nystagmus was significantly more common in the white European population than in the Asian (Indian, Pakistani, other Asian backgrounds) population (P = 0.004). CONCLUSIONS The findings suggest that nystagmus is more common in the general population than previously thought. This may be of significance in resource allocation and health care planning.
160 citations
TL;DR: This review discusses genomic and non-genomic actions of the androgen receptor, as well as their co-regulators, and explores several clinically relevant aspects of the molecular biology of theandrogen receptor and its co-Regulators.
TL;DR: At a time when evidence suggests that up to 94% of interventions may not benefit the patient, the authors urge that at least one of the randomised trials comparing CEA with CAS in asymptomatic patients includes an adequately powered third limb for BMT.
TL;DR: This research presents a novel and scalable approach called “Smartphone Diabetology” that allows for real-time, location-based assessment of the insulin resistance of children and young people with diabetes.
Abstract: Karin Langea, Peter Swiftb, Ewa Pankowskac and Thomas Danned aDepartment of Medical Psychology, Hannover Medical School, OE 5430, 30625, Hannover, Germany; bChildrens Hospital, Leicester Royal Infirmary, Leicester, LE1 5WW, UK; cThe Institute of Diabetology, ul. Żeganska 46a, 04-736, Warszawa, Poland; and dDiabetes Centre for Children and Adolescents at the Kinderund Jugendkrankenhaus, Auf der Bult, Janusz-Korczak-Allee 12, 30173, Hannover, Germany
TL;DR: Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic pain.
Abstract: Opioid receptors are currently classified as µ (mu: mOP), δ (delta: dOP), κ (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. Simultaneous targeting of MOP and DOP can be accomplished by: (i) co-administering two selective drugs, (ii) administering one non-selective drug, or (iii) designing a single drug that specifically targets both receptors; a bivalent ligand. Bivalent ligands generally contain two active centres or pharmacophores that are variably separated by a chemical spacer and there are several interesting examples in the literature. For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain.
TL;DR: The development of a HeLa-specific DNA diagnostic test: a single duplex detection PCR assay targeting an L1 retrotransposon insertion that appears to be unique to the HeLa cell line is reported.
Abstract: The HeLa cell line is the oldest, most widely distributed, permanent human cell line. As a nearly ubiquitous inhabitant of laboratories using tissue culture techniques, its aggressive growth characteristics make it a problematic contaminant that can overgrow less robust cell lines. Consequently, HeLa contamination is common in both the research laboratory and cell line repository contexts, and its detection is hampered by the lack of a rapid, sensitive and robust assay. Here we report the development of a HeLa-specific DNA diagnostic test: a single duplex detection PCR assay targeting an L1 retrotransposon insertion. All HeLa clones from a geographically diverse panel were positive by this assay, and the particular L1 insertion we identified appears to be unique to the HeLa cell line. The assay can detect very low levels of HeLa contamination (<1%), and can be performed on un-purified cell pellets, allowing rapid routine screening.
TL;DR: Ovarian senescence occurs gradually during the fourth and fifth decades of life, leading to menopause at an average age of about 51 years, with decreases in the levels of estrogens and androgens.
TL;DR: Existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.
Abstract: There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.
TL;DR: HIV patients should be considered for ASCT according to the same criteria adopted for HIV(-) lymphoma patients within the highly active antiretroviral therapy era.
TL;DR: Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial At, suggesting a depot-specific as well as a disease-linked response to inflammation.
Abstract: Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated.
Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappa B (NF kappa B) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects.
Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies.
Results: Western blotting showed epicardial AT had significantly higher NF kappa B, inhibitory-kappa B kinase (IKK)-gamma, IKK beta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P < 0.05].
Conclusion: Epicardial AT from patients with CAD shows increased NF kappa B, IKK beta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NF kappa B and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue. (J Clin Endocrinol Metab 94: 261-267, 2009)
TL;DR: While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies.
TL;DR: The data confirm for the first time a definite association of heterozygous COL4A3/COL4A4 mutations with familial microscopic haematuria, thin basement membrane nephropathy and the late development of familial proteinuria, CRF, and ESRD, due to FSGS, indicating that the term 'benign familial haematureia' is a misnomer, at least in this cohort.
Abstract: Background. Heterozygous mutations in the COL4A3/ COL4A4 genes are currently thought to be responsible for familial benign microscopic haematuria and maintenance of normal long-term kidney function. Methods. We report on 11 large Cypriot pedigrees with three such mutations. A total of 236 at-risk family members were genetically studied, and 127 (53.8%) carried a heterozygous mutation. Clinico-pathological correlations were available in all of these patients. Renal biopsies in 21 of these patients all showed various stages of focal, segmental glomerulosclerosis (FSGS). Thirteen of these biopsies were also studied with EM and showed thinning of the glomerular basement membrane. Results. Mutation G1334E (COL4A3) was found in six pedigrees, mutation G871C (COL4A3) in four and mutation 3854delG (COL4A4) in one pedigree. Clinical and laboratory correlations in all 127 mutation carriers (MC) showed that microscopic haematuria was the only urinary finding in patients under age 30. The prevalence of ‘haematuria alone’ fell to 66% between 31 and 50 years, to 30% between 51 and 70 and to 23% over age 71. Proteinuria with CRF developed on top of haematuria in 8% of all MC between 31 and 50 years, to 25% between 51 and 70 years and to 50% over 71 years. Altogether 18 of these 127 MC (14%) developed ESRD at a mean age of 60 years. Two members with different mutations married, and two of their children inherited both mutations and developed adolescent, autosomal recessive Alport syndrome (ATS), confirming that these mutations are pathogenic. Conclusions. Our data confirm for the first time a definite association of heterozygous COL4A3/COL4A4 mutations with familial microscopic haematuria, thin basement membrane nephropathy and the late development of familial proteinuria, CRF, and ESRD, due to FSGS, indicating that the term ‘benign familial haematuria’ is a misnomer, at least in this cohort. A strong hypothesis for a causal relationship between these mutations and FSGS is also made. Benign familial haematuria may not be so benign as commonly thought.
TL;DR: A multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis.
Abstract: HB Mortensen, PGF Swift, RW Holl, P Hougaard, L Hansen, H Bjoerndalen, CE de Beaufort, M Knip. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis.
Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).
Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally.
Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta-cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C-peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C-peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non-white Caucasian ethnicity (p = 0.002).
Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.
TL;DR: A dual requirement for TNC and MMP in enhancing breast cancer cell invasion is demonstrated and a significant role is identified for the tumour-associated T NC-16 and TNC-14/16 in promoting tumour invasion, although these isoform-specific effects appear to be mediated through MMP-independent mechanisms.
Abstract: Introduction
The stromal microenvironment has a profound influence on tumour cell behaviour. In tumours, the extracellular matrix (ECM) composition differs from normal tissue and allows novel interactions to influence tumour cell function. The ECM protein tenascin-C (TNC) is frequently up-regulated in breast cancer and we have previously identified two novel isoforms – one containing exon 16 (TNC-16) and one containing exons 14 plus 16 (TNC-14/16).
Leicester Royal Infirmary1, University of Western Australia2, Centre Hospitalier de Luxembourg3, Royal Children's Hospital4, University of Chieti-Pescara5, University of Toronto6, Boston Children's Hospital7, Peijas Hospital8, Children's Hospital Los Angeles9, Haukeland University Hospital10, University of Bergen11, Royal Hospital for Sick Children12, Nihon University13, University of Parma14, Novo Nordisk15
TL;DR: Target setting in intensive insulin management is associated with metabolic control in the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005.
Abstract: Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Aman J, Aanstoot H-J, Castano L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njolstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005.
Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.
Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally.
Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001).
Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.
TL;DR: These data demonstrate excellent absolute and relative reliability of CBFV, whereas ARI is of comparable reliability with the measurement of HR, but more work is needed to understand the determinants of intra-subject variability in autoregulatory parameters.
Abstract: Spontaneous fluctuations in BP (blood pressure) and subsequent change in CBFV (cerebral blood flow velocity) in the MCA (middle cerebral artery) can be used to assess dynamic cerebral autoregulation using transfer function analysis; however, the reliability of this technique has not been assessed, in particular the contribution of intra-subject variability relative to inter-subject variability. Three bilateral CBFV, BP and RR interval recordings were performed in ten healthy volunteers on four separate occasions over a 2-week period. Data were analysed to provide the ARI (autoregulatory index), CBFV, RAP (resistance-area product) and CrCP (critical closing pressure). We also measured systolic and diastolic BP, and resting HR (heart rate). We calculated the SEM (standard error of measurement) and the ICC (intra-class correlation coefficient) and their 95% CIs (confidence intervals) for each parameter to assess their absolute (intra-subject) and relative (inter-subject) reliability. The CV (coefficient of variation) of SEM ranged from 1.7% (for CBFV) to 100.0% (for RAP), whereas the ICC was 0.8 for CBFV and diastolic BP. These data demonstrate excellent absolute and relative reliability of CBFV, whereas ARI is of comparable reliability with the measurement of HR. Using these results it is possible to determine the sample size required to demonstrate a change in ARI, with a sample of 45 subjects in each group required to show a change in ARI of 1, whereas to detect a change in ARI >2 would require only 11 subjects per group. The results of the present study could be valuable to the future planning of cerebral autoregulation studies, but more work is needed to understand the determinants of intra-subject variability in autoregulatory parameters.
TL;DR: Compared to RF and CT, MTA induced microscopically well‐demarcated lesions, with no intralesional hepatocyte survival, which may be due to the relatively prolonged treatment times needed, allowing thermal energy to dissipate via blood flow.
TL;DR: Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.
Abstract: Background—Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation– Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. Methods and Results—CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, 0.1 mm Hg [95% CI, 1.8 to 1.6], P0.9; change in brachial pulse pressure, 0.02 mm Hg [95% CI, 1.6 to 1.6], P0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, 0.5 mm Hg [95% CI, 2.3 to 1.2], P0.5; change in aortic pulse pressure, 0.4 mm Hg [95% CI, 1.9 to 1.0], P0.6) and had no influence on augmentation index (change in augmentation index, 0.4%; 95% CI, 1.7 to 0.8; P0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, 1.3 to 1.8; P0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure–lowering treatment strategy in the factorial design. Conclusions—Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA. (Circulation. 2009;119:53-61.)
TL;DR: Whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers between pediatric diabetes centers is explored.
Abstract: BACKGROUND: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers These differences cannot be accounted for by differences in demographic, medical, or treatment variables Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers METHODS: An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory All individuals with diabetes aged 11-18 yr (494% female), with duration of diabetes of at least 1 yr, were invited to participate Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project RESULTS: Older participants (p < 0001) and females (p < 0001) reported less physical activity Physical activity was associated with positive health perception (p < 0001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis The more time spent on the computer (r = 006; p < 005) and less time spent doing school homework (r = -009; p < 0001) were associated with higher HbA1c Between centers, there were significant differences in reported physical activity (p < 0001) and sedentary behavior (p < 0001), but these differences did not account for center differences in metabolic control CONCLUSIONS: Physical activity is strongly associated with psychological well-being but has weak associations with metabolic control Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences
TL;DR: The AspECT trial is the biggest, multicentre, randomised controlled clinical trial looking at the long-term chemoprevention effect of esomeprazole with or without aspirin, and more than 85% of the participants tolerated the medications at the initial intended doses, and the drop-out rate has been 7%.
Abstract: Oesophageal cancer is on the rise and often present in an advanced state. Advances in surgical techniques, chemotherapy and radiotherapy have not changed the prognosis of oesophageal cancer over the last 20 years. With the unravelling of molecular biology of carcino-genesis in the oesophagus, there is a need for a paradigm shift from cancer treatment to prevention. Barrett's oesophagus is the commonest pre-malignant condition for development of oesophageal adenocarcinomas and is eminently suitable for the study of chemoprevention strategies. Now in its third year, the AspECT trial is the biggest, multicentre, randomised controlled clinical trial looking at the long-term chemopre-vention effect of esomeprazole with or without aspirin. More than 85% of the participants tolerated the medications at the initial intended doses, and the drop-out rate has been 7%; the interim analysis is due in 2011.
TL;DR: It remains questionable whether the observed 9% risks can be justified in any asymptomatic patient with unilateral carotid disease, but it is suggested that staged CAS plus CABG is an attractive and less invasive alternative to CEAPlusCABG.