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Biomedical subjects

J Edwards

Publications and source records attributed to J Edwards.

At least 19 recordsLinked to original sources
PubMed2006

Sampling for collection of central line-day denominators in surveillance of healthcare-associated bloodstream infections.

OBJECTIVE: To determine the feasibility of estimating the number of central line-days at a hospital from a sample of months or individual days in a year, for surveillance of healthcare-associated bloodstream infections. DESIGN: We used data reported to the National Nosocomial Infections Surveillance system in the adult and pediatric intensive care unit component for 1995-2003 and data from a sample of hospitals' daily counts of device use for 12 consecutive months. We calculated the percentile error as the central line-associated bloodstream infection percentile based on rates per line-days minus the percentile based on rates per estimated line-days. SETTING AND PARTICIPANTS: A total of 247 hospitals were used for sampling whole months and 12 hospitals were used for sampling individual days. RESULTS: For a 1-month sample of central line-days data, the median percentile error was 3.3 (75th percentile, 7.9; 90th percentile, 15.4). The percentile error decreased with an increase in the number of months sampled. For a 3-month sample, the median percentile error was 1.4 (75th percentile, 4.3; 95th percentile, 8.3). Sampling individual days throughout the year yielded lower percentile errors than sampling an equivalent fraction of whole months. With 1 weekday sampled per week, the median percentile error ranged from 0.65 to 1.40, and the 90th percentile ranged from 2.8 to 5.0. Thus, for 90% of units, collecting data on line-days once a week provides an estimate within +/-5 percentile points of the true line-day rate. CONCLUSION: Sample-based estimates of central line-days can yield results that are acceptable for surveillance of healthcare-associated bloodstream infections.

Adult↗
PubMed2006

Insertion mutation at the C-terminus of the serotonin transporter disrupts brain serotonin function and emotion-related behaviors in mice.

The 5-hydroxytryptamine transporter (5-HTT) regulates 5-hydroxytryptamine (5-HT) neurotransmission by removing 5-HT from the synaptic cleft. Emerging evidence from clinical and genetic studies implicates the 5-HTT in various neuropsychiatric conditions, including anxiety and depression. Here we report that a 5-HTT null mutant mouse line was generated by gene trapping that disrupted the sequence encoding the C-terminus of 5-HTT. This mutation resulted in significant reduction of 5-HTT mRNA and loss of 5-HTT protein. Brain levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were markedly decreased in C-terminus 5-HTT -/- mice, while 5-HT uptake or 5-HT content in platelets was absent. Behavioral phenotyping showed that C-terminus 5-HTT -/- mice were normal on a screen for gross behavioral, neurological, and sensory functions. In the tail suspension test for depression-related behavior, C-terminus 5-HTT -/- mice showed increased immobility relative to their +/+ controls. By comparison, a previously generated line of 5-HTT -/- mice lacking exon 2, encoding the N-terminus of the 5-HTT, showed abnormally high immobility in response to repeated, but not acute, exposure to the tail suspension test. In a novel, brightly-lit open field, both C-terminus 5-HTT -/- mice and N-terminus 5-HTT -/- mice displayed decreased center time and reduced locomotor activity compared with their +/+ controls. Both mutant lines buried significantly fewer marbles than their +/+ controls in the marble burying test. These findings further demonstrate the neurobiological functions of the 5-HTT and add to a growing literature linking genetic variation in 5-HTT function with emotional abnormalities.

Analysis of Variance↗
PubMed2006

A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy.

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.

Adult↗
PubMed2006

Observer variation in immunohistochemical analysis of protein expression, time for a change?

AIM: Immunohistochemical analysis of protein expression is central to most clinical translational studies and defines patient treatment or selection criteria for novel drugs. Interobserver variation is rarely analysed despite recognition that this is a key area of potential inaccuracy. Therefore our aim was to examine observer variation and suggest the revision of current standards. METHODS AND RESULTS: We analysed inter- and intra-observer variation, by interclass correlation coefficient (ICCC) and kappa statistics, in 8661 samples. Intra-observer assessment of nuclear, cytoplasmic and membrane staining for seven proteins in 1323 samples resulted in an ICCC of 0.94 and a kappa-value of 0.787. Interobserver reproducibility, assessed on 28 proteins by seven observer pairs in 8661 carcinomas, gave an ICCC of 0.90 and a kappa-value of 0.70. No significant effect of either antibody or cellular compartmentalization was observed. CONCLUSION: We have demonstrated that ICCC is a consistent method to assess observer variation when a continuous scoring system is used, compared with kappa statistics, which depends on a categorical system. Given the importance of accurate assessment of protein expression in diagnostic and experimental medicine, we suggest raising thresholds for observer variation: ICCC of 0.7 should be regarded as the minimum acceptable standard, ICCC of 0.8 as good and ICCC of > or = 0.9 as excellent.

Biomarkers, Tumor↗
PubMed2006

Comparison of hepatitis C treatment patterns in patients with and without psychiatric and/or substance use disorders.

Hepatitis C virus (HCV) infection is more frequent in veterans than in nonveterans. Up to 85% of HCV-infected veterans have psychiatric and/or substance use (SU) co-morbidities which, prior to the 2002 NIH Consensus Conference, were considered relative contraindications to antiviral therapy, assuming a poor adherence. With the objective of evaluating the validity of this assumption, we compared eligibility, completion and response to antiviral therapy in HCV-infected veterans with and without these comorbidities. Veterans who were anti-HCV-positive and had been seen at least once in the liver clinic (between October 1999 and June 2002) were identified through the CT-VAHCS database. Records were reviewed for patient demographics and status of liver disease, assessment of treatment eligibility, type of therapy, completion of therapy and virological response. Patients with active mental illness (MI) or SU were compared with those without these comorbidities (controls). Of 697 anti-HCV-positive-patients, 647 HCV-RNA-positive patients were included, 294 with MI/SA and 353 controls. Patient demographics, viral and liver disease characteristics were comparable between groups. Patients with MI/SA were considered ineligible for therapy more frequently (53%vs 39%, P < 0.001) and were treated less frequently (21%vs 28%, P = 0.03) than controls. However, completion of therapy (72%vs 59%) and sustained virological response (SVR) (20%vs 25%) did not differ significantly between groups. HCV-infected veterans with MI/SA are being offered therapy and treated less often than those without such co-morbidities, however therapy completion and SVR rates are similar, challenging the perception that adherence is poorer in this patient population.

Adult↗
PubMed2006

Asian MODY: are we missing an important diagnosis?

AIMS: Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes where correct diagnosis alters treatment, prognosis and genetic counselling. The first UK survey of childhood MODY identified 20 White, but no Asian children with MODY. We hypothesized that MODY causes diabetes in UK Asians, but is underdiagnosed. METHODS: Children with dominant family histories of diabetes were recruited. Direct sequencing for mutations in the two most common MODY genes; HNF1A (TCF1) and GCK was performed in autoantibody-negative probands. We also compared MODY testing data for Asian and White cases from the Exeter MODY database, to 2001 UK census data. RESULTS: We recruited 30 families and identified three Asian families with MODY gene mutations (two HNF1A, one GCK) and three White UK families (two HNF1A, one GCK). Heterozygous MODY phenotypes were similar in Asians and Whites. Only eight (0.5%) of 1369 UK referrals for MODY testing were known to be Asian, but in 2001 Asians represented 4% of the English/Welsh population and have a higher prevalence of diabetes. CONCLUSIONS: We identified three cases of childhood MODY in UK Asians and demonstrated reduced rates of MODY testing in Asians, which has negative implications for treatment. It is unclear why this is. MODY should be considered in autoantibody-negative Asian diabetes patients lacking evidence of insulin resistance.

Adolescent↗
PubMed2006

Randomized controlled trial of a cannabis-focused intervention for young people with first-episode psychosis.

OBJECTIVE: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). METHOD: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. RESULTS: There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. CONCLUSION: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.

Adolescent↗
PubMed2006

Substance misuse in first-episode psychosis: 15-month prospective follow-up study.

BACKGROUND: Well-designed prospective studies of substance misuse in first-episode psychosis can improve our understanding of the risks associated with comorbid substance misuse and psychosis. AIMS: To examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis. METHOD: The study was a prospective 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services. RESULTS: Substance misuse was independently associated with increased risk of in-patient admission, relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors. Substance misuse was not associated with remission or time to remission of positive symptoms. Heavy substance misuse was associated with increased risk of in-patient admission, relapse and shorter time to relapse. CONCLUSIONS: Substance misuse is an independent risk factor for a problematic recovery from first-episode psychosis.

Adult↗
PubMed2006

Molecular modeling studies of the binding characteristics of phosphates to sevelamer hydrochloride--assessing a novel technique to reduce phosphates contamination.

Recent advances in the use of polymeric materials for the remediation of phosphate from aqueous systems, including biological environments, have prompted the use of computational techniques to determine which methods are feasible to model such complex systems and to model the mechanism of binding action. In particular, Sevelamer Hydrochloride (Renagel) is used as our model polymer. A relatively simple system is constructed with a dimer of Sevelamer Hydrochloride and four phosphate ions used for capture. This work reports on molecular dynamics and Monte Carlo simulations used to determine average structure, and points of intermolecular interaction, and calculate changes in volume after the successful capture of phosphate in our model. Our resulting volume changes are of the order of 20-25%, in comparison to experimental swelling measurements on similar systems, which have an average swelling of 50-60% in aqueous media.

Models, Molecular↗
PubMed2005

Raf-1 expression may influence progression to androgen insensitive prostate cancer.

BACKGROUND: Recent evidence has implicated the MAP kinase pathway with the development of androgen insensitive prostate cancer (AIPC). We have previously reported gene amplification of critical members of this pathway with the development of androgen insensitive disease. METHODS: Protein expression of Raf-1 was analyzed using immunohistochemistry (IHC) in a database of 65 paired tumor specimens obtained before and after the development of AIPC and correlated with other members of the pathway. RESULTS: Patients whose Raf-1 expression rose with development of AIPC had a significantly shorter median time to biochemical relapse compared to those whose expression fell or remained unchanged (1.16 vs. 2.62 years, P = 0.0005). In AIPC tumors, expression of Raf-1 correlated significantly with expression of HER2 and with expression of c-fos. CONCLUSIONS: We conclude that the HER2/Raf-1/AP-1 axis may promote the development of AIPC, leading to early relapse. Members of the pathway may act as novel therapeutic targets for patients.

Androgens↗
PubMed2005

Single dose oral rofecoxib for postoperative pain.

BACKGROUND: Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. So far, other similar anti-inflammatory drugs are unaffected. Further information is available at www.vioxx.com. Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that was licensed in the UK and the US for acute pain treatment and is associated with fewer gastrointestinal adverse events than conventional NSAIDs. Rofecoxib is believed to be at least as effective as conventional non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of rofecoxib for moderate to severe postoperative pain, and to compare its effectiveness with other analgesics used for treating acute pain. SEARCH STRATEGY: We searched Cochrane Library (Issue 1, 2002), MEDLINE (1966 to March 2002), Biological Abstracts (1985 to Dec 2001), CINAHL (1982 to Dec 2001), Psychinfo (1967 to Jan 2002), PubMed (March 2001) and the Oxford pain database. SELECTION CRITERIA: Randomised controlled trials of adult patients who received either rofecoxib or placebo for postoperative pain. DATA COLLECTION AND ANALYSIS: Trials were quality scored and the data extracted by two reviewers independently. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was extracted and converted into dichotomous information yielding the number of patients with at least 50% pain relief. These derived results were used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Seven studies met the inclusion criteria. All the trials were funded by Merck & Company, the manufacturer of rofecoxib. In total, 667 patients were treated with rofecoxib 50 mg and 315 with placebo. The NNT for rofecoxib 50 mg was 2.2 (95% CI 1.9 to 2.4), ie, for every two patients treated with rofecoxib 50 mg, one patient experienced at least 50% pain relief that would not have done had they received placebo. All the studies were of short duration, and reported adverse events occurred less frequently with rofecoxib 50 mg than with placebo. AUTHORS' CONCLUSIONS: Rofecoxib 50 mg (a dose 2 to 4 times the standard daily dose for chronic pain) is an effective single dose oral analgesic for acute postoperative pain.

Administration, Oral↗
PubMed2005

Inflammatory arthritis and dermatitis in thymectomized, CD25+ cell-depleted adult mice.

OBJECTIVE: To investigate the effect of CD25+ or CTLA-4(+) cell depletion on the natural history of collagen-induced and spontaneous arthritis in male DBA1/J mice. METHODS: Male DBA/1J mice were treated with anti-CD25 depleting antibody (PC61) or isotype control (GL113), or with anti-CTLA-4 depleting antibody (4F10) at various time-points peri- and post-immunization with bovine collagen type II, emulsified in adjuvant. In order to develop a model system in which long-term depletion of CD25+ regulatory T cells can be achieved prior to immunization, adult male DBA/1J mice were thymectomized prior to administration of either PC61 or GL113. An ELISA demonstrated that PC61 and GL113 antibodies were undetectable by 21 days after administration and FACS analysis confirmed the long-term depletion of CD25+ cells in peripheral blood. RESULTS: In the thymectomized mice treated with PC61, the CD25+ population was depleted and a spontaneous arthritis developed (P = 0.03). In the non-thymectomized mice, administration of CTLA-4-depleting antibody prior to immunization exacerbated arthritis in mice immunized with bovine collagen type II emulsified in incomplete Freund's adjuvant (P < 0.01). However, no significant difference in the natural history of arthritis was evident in mice treated with CD25-depleting antibody (PC61) compared with control antibody (GL113). CONCLUSIONS: Two separate models implicate CD25+ CTLA-4(+) constitutive cells in suppression of arthritis in susceptible DBA/1 males: exacerbation of collagen-induced arthritis following CTLA-4 depletion at the start of induction and spontaneous arthritis in the thymectomy/CD25+ depletion model.

Animals↗
PubMed2005

Long-range temporal correlations in the spontaneous spiking of neurons in the hippocampal-amygdala complex of humans.

The spontaneous or background discharge patterns of in vivo single neuron is mostly considered as neuronal noise, which is assumed to be devoid of any correlation between successive inter-spike-intervals (ISI). Such random fluctuations are modeled only statistically by stochastic point process, lacking any temporal correlation. In this study, we have investigated the nature of spontaneous irregular fluctuations of single neurons from human hippocampus-amygdala complex by three different methods: (i) detrended fluctuation analysis (DFA), (ii) multiscale entropy (MSE), (iii) rate estimate convergence. Both the DFA and MSE analysis showed the presence of long-range power-law correlation over time in the ISI sequences. Moreover, we observed that the individual spike trains presented non-random structure on longer time-scales and showed slow convergence of rate estimates with increasing counting time. This power-law correlation and the slow convergence of statistical moments were eliminated by randomly shuffling the ISIs even though the distributions of ISIs were preserved. Thus the power-law relationship arose from long-term correlations among ISIs that were destroyed by shuffling the data. Further, we found that neurons which showed long-range correlations also showed statistically significant correlated firing as measured by correlation coefficient or mutual information function. The presence of long-range correlations indicates the history-effect or memory in the firing pattern by the associative formation of a neuronal assembly.

Action Potentials↗
PubMed2005

Comparison of olanzapine and risperidone in 367 first-episode patients with non-affective or affective psychosis: results of an open retrospective medical record study.

INTRODUCTION: Previous studies comparing olanzapine (OLZ) and risperidone (RIS) have tended to focus on multiple-episode patients, with no studies examining their comparative efficacy in a non-selective sample of first-episode psychosis. METHODS: The Early Psychosis Prevention and Intervention Centre in Australia had admitted 786 first-episode psychosis (FEP) patients between 1998-2000. Data were collected from the medical records (MR) of 367 patients, which met inclusion criteria. The primary objective was to evaluate the efficacy of OLZ vs. RIS as measured by CGI-S, CGI-BP (symptomatic level), GAF and SOFAS (functioning level). RESULTS: 367 FEP patients were entered into the study, 278 in the RIS- (2.7 mg/day) and 89 in the OLZ group (10.2 mg/day). No between-group differences were found in non-affective FEP (n = 273). In affective FEP patients (n = 94), mainly treated for acute mania (86.7 %), OLZ treatment was related to better response on the symptomatic (CGI-S; p = .002), but not on the functioning level (GAF and SOFAS; ns). There were trends in the OLZ group towards a higher rate of remission of positive symptoms ( p = .054) and a shorter treatment duration to reach this remission in affective FEP patients ( p = .077). More extrapyramidal side effects ( p <.001) were related to RIS and more weight gain to OLZ-treatment ( p <.001). DISCUSSION: Despite the limitations of a retrospective MR design, study results suggest equal therapeutic efficacy of OLZ and RIS in non-affective FEP and some therapeutic advantages of OLZ compared to RIS in affective FEP patients, especially in those with acute mania. Results may serve as hypotheses for future randomised controlled trials.

Adolescent↗
PubMed2005

Virtual colonoscopy: issues in implementation.

The following issues and requirements related to the implementation of a CT colonography (CTC) service are important: (i) policies are needed regarding the indications for CTC. Concomitant with this is the need for education of potential referrers and patients. Expectations of the procedure, particularly by general practitioners, may be unrealistic and indications for referral may otherwise be inappropriate. At present there is not general acceptance of CTC for screening asymptomatic persons; (ii) a flexible approach to CT protocols is useful, dependent on the indication for and clinical context of referral, the age and body habitus of the patient; (iii) attention to the issues related to the special skills required by the reporting radiologist. While there is a temptation to regard CTC interpretation as an extension of skills used in interpreting other cross-sectional images, there is a need to realise that there are skills required specific to CTC and there should be adequate provision for training; (iv) matters related to reporting, such as reporting format, and lesions that will be reported/not reported; and (v) informed consent from the patient. Information should be provided with regard to the limitations of CTC, the implications of a positive finding and radiation dosage.

Colonic Diseases↗
PubMed2005

Ability of a nurse specialist to diagnose simple headache disorders compared with consultant neurologists.

OBJECTIVE: To compare the ability of a headache nurse specialist and consultant neurologists in diagnosing tension-type headache and migraine. METHODS: An experienced neurology ward sister was trained in the differential diagnosis of headache disorders. Over six months, patients with non-acute headache disorders and role players trained to present with benign or sinister headaches were seen by both the nurse and a consultant neurologist. Both reached independent diagnoses of various headache disorders. RESULTS: Consultants diagnosed 239 patients with tension-type headache (47%), migraine (39%), or other headache disorders (14%). The nurse agreed with the consultant in 92% of cases of tension-type headache, 91% of migraine, and 61% of other diagnoses. Where the nurse did not agree with the diagnosis, most would have been referred for a consultant opinion. Both the nurse and the doctors misdiagnosed the same three of 13 role players. The investigation rate of the consultants varied between 18% and 59%. Only one clinically relevant abnormality was found on head scans and this was strongly suspected clinically. CONCLUSIONS: A headache nurse specialist can be trained to diagnose tension-type headache and migraine. A nationwide nurse led diagnostic headache service could lead to substantial reduction in neurology waiting times.

Adult↗
PubMed2004

Single dose oral indometacin for the treatment of acute postoperative pain.

BACKGROUND: Indometacin is a non-steroidal anti-inflammatory drug (NSAID) used most commonly for the treatment of inflammation and pain resulting from rheumatic disease (arthritis), and less commonly in postoperative pain management. When taken for chronic pain conditions, indometacin has been associated with a high incidence of adverse events. The benefits and harms of orally-administered indometacin for postoperative pain are not clear. OBJECTIVES: To determine the efficacy of a single dose of oral indometacin compared with placebo in treating acute postoperative pain in adults, and to analyse information relating to adverse events. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 3, 2004), MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were sought from the reference lists of retrieved reports. SELECTION CRITERIA: Studies were included in the review if they were randomised, double blind, placebo-controlled clinical trials using a single oral dose of indometacin in adults with acute postoperative pain. DATA COLLECTION AND ANALYSIS: Trials were assessed independently by two authors. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. The relative benefit for at least 50% pain relief was calculated. MAIN RESULTS: One trial of 59 women with post-episiotomy pain met the inclusion criteria. The dose of indometacin assessed against placebo was 50 mg, and the results concluded that indometacin was not significantly better than placebo for relieving postoperative pain at four to six hours. There was insufficient information to conduct further efficacy analyses or assess adverse events. REVIEWERS' CONCLUSIONS: Conclusions about the clinical efficacy of indometacin for postoperative cannot be made until more trials are conducted for a variety of surgical procedures, and different doses of indometacin are assessed.

Administration, Oral↗