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Biomedical subjects

A Gray

Publications and source records attributed to A Gray.

At least 19 recordsLinked to original sources

Cost of cardiovascular diseases in the United Kingdom.

OBJECTIVE: To estimate the economic burden of cardiovascular disease (CVD) in the United Kingdom, including health and non-healthcare costs, and the proportion of total CVD cost due to coronary heart disease (CHD) and cerebrovascular disease. DESIGN AND SETTING: Prevalence-based approach to assess CVD-related costs from a societal perspective. PATIENTS: All UK residents in 2004 with CVD (International classification of diseases, 10th revision (ICD-10) codes I00-I99) and subgroups with CHD (ICD-10 codes I20-I25) or cerebrovascular disease (ICD-10 codes I60-I69). MAIN OUTCOME MEASURES: Healthcare costs were estimated from expenditure on community health and social services, accident and emergency care, hospital care, rehabilitation and drugs. Non-healthcare costs were estimated from data on informal care and from productivity losses arising from morbidity and premature death. RESULTS: CVD cost the UK economy 29.1 billion pound in 2004, with CHD and cerebrovascular disease accounting for 29% (8.5 billion pound) and 27% (8.0 billion pound) of the total, respectively. The major cost component of CVD was health care, which accounted for 60% of the cost, followed by productivity losses due to mortality and morbidity, accounting for 23%, with the remaining 17% due to informal care-related costs. CONCLUSIONS: CVD is a leading public health problem in the UK measured by the economic burden of disease. This study identified the size and main components of that burden, and will help to inform decisions about research priorities and to monitor the impact of policy initiatives.

Absenteeism↗

Collapse query cause: the management of adult syncope in the emergency department.

Syncope is a commonly encountered problem in the emergency department (ED). Its causes are many and varied, some of which are potentially life threatening. A review was carried out of relevant papers in the available literature, and this article attempts to assimilate current evidence relating to ED management. While the cause of syncope can be identified in many patients, and life threatening conditions subsequently treated, a risk stratification approach should be taken for those in whom a cause is not identified in the ED. Aspects of the history and examination that may help identify high risk patients are explored and the role of investigations to aid this stratification is discussed. Identifying a cardiac cause for syncope is a poor prognostic indicator. Patients with unexplained syncope who have significant cardiac disease should therefore be investigated thoroughly to determine the nature of the underlying heart disease and the cause of syncope, although presently there is little evidence that this improves their dismal prognosis. This risk stratification approach has led to the development of several clinical decision rules, which are discussed along with current international guidelines on syncope management. This review suggests that presently the American College of Emergency Physicians guidelines are the most useful aids specific to the management of syncope in the ED; however, the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) score may also be a useful ED risk stratification tool.

Adult↗

Use of non-invasive ventilation in UK emergency departments.

AIM: To describe the current use of non-invasive ventilation in UK emergency departments. METHODS: A structured questionnaire was sent to all UK emergency departments assessing 25,000 new patients annually. RESULTS: 222 of 233 departments completed the questionnaire. 148 currently use non-invasive ventilation (NIV). Most used NIV for either cardiogenic pulmonary oedema (n = 128) or chronic obstructive pulmonary disease (n = 115). Only 49 departments have protocols for NIV use and 23 audited practice. CONCLUSION: NIV is commonly used in UK emergency departments. Practices vary significantly. One solution would be the development of guidelines on when and how to use NIV in emergency medicine practice.

Emergency Service, Hospital↗

Cost-effectiveness of referral for generic care or problem-solving treatment from community mental health nurses, compared with usual general practitioner care for common mental disorders: Randomised controlled trial.

BACKGROUND: UK general practitioners (GPs) refer patients with common mental disorders to community mental health nurses. AIMS: To determine the effectiveness and cost-effectiveness of this practice. METHOD: Randomised trial with three arms: usual GP care, generic mental health nurse care, and care from nurses trained in problem-solving treatment; 98 GPs in 62 practices referred 247 adult patients with new episodes of anxiety, depression and life difficulties, to 37 nurses. RESULTS: There were 212 (86%) and 190 (77%) patients followed up at 8 and 26 weeks respectively. No significant differences between groups were found in effectiveness at either point. Mean differences in Clinical Interview Schedule - Revised scores at 26 weeks compared with GP care were -1.4 (95% CI -5.5 to 2.8) for generic nurse care, and 1.1 (-2.9 to 5.1) for nurse problem-solving. Satisfaction was significantly higher in both nurse-treated groups. Mean extra costs per patient were 283 pound (95% CI154-411) for generic nurse care, and 315 pound (183-481) for nurse problem-solving treatment. CONCLUSIONS: GPs should not refer unselected patients with common mental disorders to specialist nurses. Problem-solving should be reserved for patients who have not responded to initial GP care.

Adolescent↗

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

OBJECTIVES: To investigate the cost-effectiveness of using prognostic information to identify patients with breast cancer who should receive adjuvant therapy. DATA SOURCES: Electronic databases from 1980 through to February 2002. A survey of clinical practice in UK cancer centres and units. Large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. REVIEW METHODS: Between six and nine databases were searched by an information expert. Evidence-based methods were used to review and select those studies and the quality of each included paper was assessed using standard assessment tools reported in the literature or piloted and developed for this study. A survey of clinical practice in UK cancer centres and units was carried out to ensure that conclusions drawn from the report could be implemented. These data, along with the information gathered in the systematic reviews, informed the methodological approach adopted for the health economic modelling. An illustrative framework was developed for incorporating patient-level prediction within a health economic decision model. This framework was applied to a large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. The data were used to estimate directly a parametric regression-based risk equation, from which a prognostic index was developed, and prognosis-specific estimates of the baseline breast cancer hazard could be observed. Published estimates of treatment effects, health service treatment costs and utilities were used to construct a decision analytic framework around this risk equation, thus enabling simulation of the effectiveness and cost-effectiveness of adjuvant therapy for all possible combinations of prognostic factors included in the model. RESULTS: The lack of good-quality systematic reviews and well-conducted studies of prognostic factors in breast cancer is a striking finding. There are no registers of studies of prognostic factors or of reviews of prognostic studies. Many of the reviews used weak methods, primary studies are similar with poor methodology and reporting of results. In addition, there is much variation in patient populations, assay methods, analysis of results, definitions used and reporting of results. Most studies appear to be retrospective and some use inappropriate methods likely to inflate outcomes such as optimising cut points and failing to test the results in an independent population. Very few reviews used meta-analysis to conduct a pooled analysis and to provide an estimate of the average size of any association. Instead, most reviews relied on vote counting. Although many prognostic models for breast cancer have been published, remarkably few have been re-examined by independent groups in independent settings. The few validation studies have been carried out on ill-defined samples, sometimes of smaller size and short follow-up, and sometimes using different patient outcomes when validating a model. The evidence from the validation studies shows support for the prognostic value of the Nottingham Prognostic Index (NPI). No new prognostic factors have been shown to add substantially to those identified in the 1980s. Improvement of this index depends on finding factors that are as important as, but independent of, lymph node, stage and pathological grade. The NPI remains a useful clinical tool, although additional factors may enhance its use. We accepted that hormone receptor status (ER) for hormonal therapy such as tamoxifen and prediction of response to trastuzumab by HER2 did not require systematic review, as the mechanism of action of these drugs requires intact receptors. There was no clear evidence that other factors were useful predictors of response and survival. The survey confirmed pathological nodal status, tumour grade, tumour size and ER status as the most clinically important factors for consideration when selecting women with early breast cancer for adjuvant systemic therapy in the UK. The protocols revealed that although UK cancer centres appear to be using the same prognostic and predictive factors when selecting women to receive adjuvant therapy, much variation in clinical practice exists. Some centres use protocols based upon the NPI whereas others do not use a single index score. Within NPI and non-NPI users, between-centre variability exists in guidelines for women for whom the benefits are uncertain. Consensus amongst units appears to be greatest when selecting women for adjuvant hormone therapy with the decision based primarily upon ER or progesterone receptor status rather than combinations of a number of factors. Guidelines as to who should receive adjuvant chemotherapy, however, were found to be much less uniform. Searches of the literature revealed only five published papers that had previously examined the cost-effectiveness of using prognostic information for clinical decision-making. These studies were of varying quality and highlight the fact that economic evaluation in this area appears still to be in its infancy. By combining methodologies used in determining prognosis with those used in health economic evaluation, it was possible to illustrate an approach for simulating the effectiveness (survival and quality-adjusted survival) and the cost-effectiveness associated with the decision to treat individual women or groups of women with different prognostic characteristics. The model showed that effectiveness and cost-effectiveness of adjuvant systemic therapy have the potential to vary substantially depending upon prognosis. For some women therapy may prove very effective and cost-effective, whereas for others it may actually prove detrimental (i.e. the reductions in health-related quality of life outweigh any survival benefit). CONCLUSIONS: Outputs from the framework constructed using the methods described here have the potential to be useful for clinicians, attempting to determine whether net benefits can be obtained from administering adjuvant therapy for any presenting woman; and also for policy makers, who must be able to determine the total costs and outcomes associated with different prognosis based treatment protocols as compared with more conventional treat all or treat none policies. A risk table format enabling clinicians to look up a patient's prognostic factors to determine the likely benefits (survival and quality-adjusted survival) from administering therapy may be helpful. For policy makers, it was demonstrated that the model's output could be used to evaluate the cost-effectiveness of different treatment protocols based upon prognostic information. The framework should also be valuable in evaluating the likely impact and cost-effectiveness of new potential prognostic factors and adjuvant therapies.

Adjuvants, Pharmaceutic↗

Accurate determinations of alpha(s) from realistic lattice QCD.

We obtain a new value for the QCD coupling constant by combining lattice QCD simulations with experimental data for hadron masses. Our lattice analysis is the first to (1) include vacuum polarization effects from all three light-quark flavors (using MILC configurations), (2) include third-order terms in perturbation theory, (3) systematically estimate fourth and higher-order terms, (4) use an unambiguous lattice spacing, and (5) use an [symbol: see text](a2)-accurate QCD action. We use 28 different (but related) short-distance quantities to obtain alpha((5)/(MS))(M(Z)) = 0.1170(12).

Journal Article↗

Predicting postoperative analgesia outcomes: NNT league tables or procedure-specific evidence?

Number needed to treat (NNT) values have been recommended and used to assess efficacy of analgesics for acute pain management. However, the data analysed come from a variety of procedures, which may potentially hinder the interpretation of the NNT value for specific procedures. We reanalysed available NNT data with acetaminophen in relation to the magnitude of surgical injury. Acetaminophen was less effective for pain relief after orthopaedic procedures than after dental procedures. The relative risk ratio for more than 50% pain relief, compared with placebo, was only 1.87 compared with 3.77 (P<0.05). Although NNT can give a valuable overview of efficacy, this concept is not necessarily applicable to all types of surgery. We suggest that estimates of NNT should be related to specific surgical procedures.

Acetaminophen↗

The psychological impact of human papillomavirus testing in women with borderline or mildly dyskaryotic cervical smear test results: 6-month follow-up.

State anxiety (S-STAI-6), distress (GHQ-12), concern and quality of life (EuroQoL-EQ-5D) 6 months after human papillomavirus (HPV) testing in women with borderline or mildly dyskaryotic smear test results were assessed based on a prospective questionnaire study, with 6-month follow-up after the smear test result. Two centres participated in an English pilot study of HPV testing. Participants included two groups of women receiving abnormal smear test results: (tested for HPV and found to be (a) HPV positive (n=369) or (b) HPV negative (n=252)) and two groups not tested for HPV (those receiving (c) abnormal smear test results (n=102) or (d) normal smear test results (n=288)). There were no differences in anxiety, distress or health-related quality of life between the four study groups at 6 months. Levels of concern about the smear test result remained elevated in all groups receiving an abnormal smear test result, and were highest in the group untested for HPV. Predictors of concern across all groups receiving an abnormal smear test were perceived risk of developing cancer, being HPV positive or untested for HPV, sexual health worries and the smear being a woman's first smear test. The raised anxiety and distress observed in women immediately after being informed of an abnormal smear test result and that they are HPV positive was no longer evident at 6 months. Concern about the smear test result was however still raised in these women and those who tested negative for HPV, and particularly among those who did not undergo HPV testing.

Adult↗

Does body mass index affect the early outcome of primary total hip arthroplasty?

There is little evidence describing the influence of body mass index on the outcome of total hip arthroplasty (THA). Eight hundred patients undergoing primary cemented THA were followed for a minimum of 18 months. The Harris Hip Score (HHS) and Short Form 36 were recorded preoperatively and at 6 and 18 months postoperatively. In addition, other significant events were noted, namely death, dislocation, reoperation, superficial and deep infection, and blood loss. Multiple regression analysis was performed to identify whether body mass index (BMI) was an independently significant predictor of the outcome of THA. No relationship was seen between the BMI of an individual and the development of any of the complications noted. The HHS was seen to increase dramatically postoperatively in all patients. Body mass index did predict for a lower HHS at 6 and 18 months. This effect was small when compared with the overall improvements in these scores. There was no influence on the Short Form 36 component scores. On the basis of this study, we can find no justification for withholding THA solely on the grounds of BMI.

Aged↗

The regulation of membrane to cytosol partitioning of signalling proteins by phosphoinositides and their soluble headgroups.

Inositol phospholipids [PIs (phosphoinositides)] represent a group of membrane-tethered signalling molecules which differ with respect to the number and distribution of monoester phosphate groups around the inositol ring. They function by binding to proteins which possess one of several domains that bind a particular PI species, often with high affinity and specificity. PH (pleckstrin homology) domains for example possess ligand-binding pockets that are often lined with positively charged residues and which bind PIs with varying degrees of specificity. Several PH domains bind not only PIs, but also their cognate headgroups, many of which occur naturally in cells as relatively abundant cytosolic inositol phosphates. The subcellular distributions of proteins possessing such PH domains are therefore determined by the relative levels of competing membrane-bound and soluble ligands. A classic example of the latter is the PH domain of phospholipase Cdelta1, which binds both phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate. We have shown that the N-terminal PH domain of the Rho family guanine nucleotide-exchange factor, Tiam 1, binds PI ligands promiscuously allowing multiple modes of regulation. We also recently analysed the ligand-binding specificity of the PH domain of PI-dependent kinase 1 and found that it could bind abundant inositol polyphosphates such as inositol hexakisphosphate. This could explain the dual distribution of this key signalling component, which needs to access substrates at both the plasma membrane and in the cytosol.

3-Phosphoinositide-Dependent Protein Kinases↗

Influence of compacted hydrophobic and hydrophilic colloidal silicon dioxide on tableting properties of pharmaceutical excipients.

The effect of noncompacted and compacted hydrophilic as well as hydrophobic colloidal silicon dioxide (CSD) on tableting properties of three different pharmaceutical excipients used for direct compression, namely, Avicel PH 101, Starch 1500, and Tablettose 80, was investigated. Binary powder mixtures containing 0.5% CSD and 99.5% excipient were compressed on an instrumented single-punch tablet press, and the radial tensile strength/compaction load profiles were examined. The Ryshkewitch-Duckworth relationship shows that the influence of CSD on tablet strength was dependent on the hydrophobic and hydrophilic nature of the CSD and on the compaction characteristics of the excipients. Tablets from each excipient with and without CSDs were subjected to different levels of relative humidity at 20 degrees C for 7 days. The sorption isotherms and the radial tensile strengths of the tablets after the storage period showed that neither hydrophilic nor hydrophobic CSD influenced the tablet properties of Avicel PH 101, Starch 1500, and Tablettose 80. Moreover, ternary powder mixtures containing magnesium stearate as a third component were compressed in order to study the influence of CSD on the deleterious effect of magnesium stearate on the interparticle bonding. The radial tensile strength/compaction load profiles and the residual and ejection forces of tablets made from ternary mixtures showed that CSD eliminated the negative effect of magnesium stearate on interparticle bonding while maintaining the lubrication action, in a manner that was affected by its hydrophobicity/hydrophilicity and by the particle deformation properties of the excipient upon compression.

Cellulose↗

The hip trial: psychosocial consequences for mothers of using ultrasound to manage infants with developmental hip dysplasia.

BACKGROUND: The hip trial aimed to assess clinical effectiveness, economic and psychosocial costs, and benefits of ultrasound imaging (US) compared with conventional clinical assessment alone to guide the management of infants with neonatal hip instability. OBJECTIVE: To report on psychosocial consequences for mothers and the developing mother-child relationship of US, and associations between abduction splinting and maternal psychosocial distress. DESIGN: Multicentre randomised controlled trial. SETTING: Thirty three hospitals in the United Kingdom and Ireland. PARTICIPANTS, INTERVENTIONS: A total of 629 infants with neonatal hip instability randomised to US examination or clinical assessment alone before treatment decision. Questionnaires were completed by 561 (89%) mothers at 8 weeks and 494 (79%) at 1 year. MAIN OUTCOME MEASURES: Anxiety, postnatal depression, parenting stress assessed by standardised questionnaires. Maternal concerns about hip problems were assessed using the Infant hip worries inventory. RESULTS: At 8 weeks, there were no differences between US and non-US groups of the trial in maternal anxiety (mean difference (MD) -1.2, 95% confidence interval (CI) -3.2 to 0.8), depression (MD 0.0, 95% CI -0.7 to 0.8), parenting stress (MD -1.2, 95% CI -2.8 to 0.4), or other measures. The same pattern was evident at 1 year. In an explanatory analysis, early splinting was associated with increased anxiety at 8 weeks (MD 3.8, 95% CI 1.7 to 5.9) and increased level of hip worries at 8 weeks (MD 6.8, 95% CI 5.6 to 7.9) and 1 year (MD 1.3, 95% CI 0.3 to 2.4). CONCLUSIONS: Although early splinting is associated with maternal anxieties, US is not associated with any increase or reduction in psychosocial effects on mothers. Together with the clinical findings, this suggests that the use of US allows reduction in splinting rates without increased risk of adverse clinical or psychosocial outcomes.

Adult↗

Emergency department organisation of critical care transfers in the UK.

OBJECTIVES: Transport of the critically ill patient to or from the emergency department (ED) is a frequent occurrence. This study was designed to determine whether UK EDs currently have appropriate equipment, monitoring, staff training systems, and processes of care for transportation of the critically ill patient. METHODS: A postal questionnaire regarding ED transfer patients was sent to 247 UK EDs, followed by repeat mailing and telephone follow up of non-responders. RESULTS: In total, 139 EDs (56%) responded. An estimated 20-30 critically ill patients are transferred from and <20 are received by each ED annually. Processes of care are poorly developed; only 79 EDs (56%) have transfer guidelines available. Audit of transfers is ongoing in 59 EDs (42%), and critical incident reporting is ongoing in 122 (88%). There is a lack of immediately available transport equipment; for example, 17 EDs (12%) have no transport ventilator, 9 (6%) have no transport monitor, and 9 (6%) have no syringe pump. Transport equipment is invariably not standardised. Anaesthetic staff of specialist registrar (74 doctors; 53%) or senior house officer (36 doctors; 26%) grades carry out the majority of ED transfers accompanied by a D or E grade nurse. Both invariably have no formal transfer training. CONCLUSIONS: This study highlights inadequacies in provision of equipment and monitoring during interhospital transfer from the ED. Training and processes of care for transport of the critically ill are also suboptimum. Many departments are currently reviewing these processes to formalize and improve transfer training procedures and protocols.

Ambulances↗

A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.

OBJECTIVES: To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care. DESIGN: A pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care. SETTING: General practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services. PARTICIPANTS: Participants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months. INTERVENTIONS: Patients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments. MAIN OUTCOME MEASURES: Patients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis. RESULTS: Twenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence. CONCLUSIONS: The study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.

Adolescent↗

High-precision lattice QCD confronts experiment.

The recently developed Symanzik-improved staggered-quark discretization allows unquenched lattice-QCD simulations with much smaller (and more realistic) quark masses than previously possible. To test this formalism, we compare experiment with a variety of nonperturbative calculations in QCD drawn from a restricted set of "gold-plated" quantities. We find agreement to within statistical and systematic errors of 3% or less. We discuss the implications for phenomenology and, in particular, for heavy-quark physics.

Journal Article↗

Mechanism of glidants: investigation of the effect of different colloidal silicon dioxide types on powder flow by atomic force and scanning electron microscopy.

The effect of hydrophilic and hydrophobic colloidal silicon dioxide types (CSD) on the flow characteristics of microcrystalline cellulose (MCC) under different mixing conditions was macroscopically measured using the angle of repose method, the bulk and tapped densities. CSD ameliorated the flow characteristics in general, but hydrophobic CSD was more effective compared to the hydrophilic types under gentle mixing conditions. The macroscopic effect was explained on the particle level by scanning electron (SEM) and atomic force microscopy (AFM) studies. The CSD distribution on the MCC surface was more uniform for the hydrophobic type and was independent from the mixing conditions used in this study. From the cumulative adhesion force distributions of the mixtures, determined by AFM, the mean and the standard deviation of the adhesion force were calculated. The means were 44.8 nN for MCC alone, 25.2 and 28.3 nN for mixtures containing the two hydrophilic types, and 13.8 N for the hydrophobic CSD under gentle mixing conditions in a Turbula mixer. Stronger mixing in a plowshare mixer led to a further reduction to 17.5 and 17.4 nN for the two hydrophilic types, while the hydrophobic CSD showing a value of 13.9 nN was unchanged. A linear correlation between the angle of repose and the adhesion force could be established, indicating that for routine measurements of the efficiency of a glidant the simple angle of repose method is sufficient.

Chemistry, Pharmaceutical↗