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S Hill

Publications and source records attributed to S Hill.

At least 37 records · Page 2Linked to original sources

Use of pharmacoeconomics in prescribing research. Part 2: cost-minimization analysis--when are two therapies equal?

UNLABELLED: This is the second paper in a series looking at pharmacoeconomic methods. The first paper discussed how costs are identified for pharmacoeconomic studies. This article will examine one of the four main evaluation methods in health economics, cost-minimization analysis (CMA). The remaining three methods (cost-effectiveness, cost-utility and cost-benefit analysis) will be discussed in later papers. KEY MESSAGES: Cost-minimization is the appropriate form of economic analysis to carry out whenever two drugs have the same clinical effect. True equivalence studies are uncommon; a more useful approach is to assess the size of the confidence interval around the difference between treatments and determine whether it excludes clinically relevant effects. The critical issue for cost-minimization analyses is determining equi-effective doses.

Costs and Cost Analysis↗

Use of pharmacoeconomics in prescribing research. Part 4: is cost-utility analysis a useful tool?

This paper is the fourth in the 'Research Note' series describing various aspects of pharmacoeconomics in prescribing research. This article describes cost-utility analysis, and how it can be incorporated into pharmacoeconomics. While this approach has intuitive appeal, the uncertainties about the methods for estimating utilities mean that the value of cost-utility analysis in prescribing research is still to be established. Importantly, cost-utility analysis may not capture aspects of quality of life that enable meaningful comparisons between prescribing choices at an individual or societal level.

Cost-Benefit Analysis↗

eThrombosis: the 21st century variant of venous thromboembolism associated with immobility.

The association between immobility with prolonged sitting and venous thromboembolism has been recognised for > 60 yrs, most recently with long distance air travel. The case of a 32-yr-old male, in whom immobility associated with sitting for long periods at a computer represented the major provoking risk factor for his life-threatening venous thromboembolism, is presented. The authors propose the term "eThrombosis" to describe this 21st Century variant of venous thromboembolism associated with immobility from prolonged sitting. In view of the widespread use of computers in relation to work, recreation and personal communication, the potential burden of eThrombosis may be considerable.

Adult↗

Electrospray mass spectrometry for the identification of MHC class I-associated peptides expressed on cancer cells.

Electrospray ionisation (ESI) mass spectrometry (MS) has been used extensively for the detection of peptides presented by major histocompatibility complex (MHC) molecules. This review focuses on the optimisation of electrospray mass spectrometry and the use of tandem mass spectrometry to sequence MHC class I peptides. We review the isolation of MHC class I peptides from the surface of cells with particular reference to tumour cells. In addition, we also discuss the advantages and disadvantages of the methods available to concentrate and fractionate the peptides prior to analysis by electrospray mass spectrometry.

Animals↗

A comparison of the effects of bath additives on the barrier function of skin in normal volunteer subjects.

BACKGROUND: Emollients form an occlusive layer on the skin surface, reducing transepidermal water loss (TEWL), thus providing a temporary restoration of barrier function in compromised skin. This study evaluated the ability of three bath additives to reduce TEWL from compromised skin. METHODS: The stratum corneum on areas of forearm skin was removed by the repeated application of D-Squame discs. After 1 hour, baseline measurements (t = 0) of TEWL were recorded before each arm was immersed for 10 min in a warm waterbath containing one of four treatments. The arms were air-dried for 20 min and the TEWL measurements repeated. Three further TEWL measurements were made at 30-min intervals. Measurements were made using a Tewameter in a controlled atmosphere. RESULTS: There was little difference between the products in terms of changes in mean TEWL values. However, when expressed relative to t = 0 values, some differences became apparent. The mean values for sites treated with Balmandol were lower than the other sites at 60, 90 and 120 min. When analysed by using the summary statistic AUC (area under the curve), the difference between Balmandol and water and also Balmandol and Eucerin was statistically significant (p < 0.05). CONCLUSION: These results would suggest that Balmandol has a greater effect on barrier function (as assessed by measurement of a reduction in TEWL values) than Eucerin.

Adult↗

A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease.

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

AIDS-Related Opportunistic Infections↗

Quantum melting of the quasi-two-dimensional vortex lattice in kappa- (ET)2Cu(NCS)(2).

We report torque magnetization measurements in regions of the mixed state phase diagram ( B approximately mu(o)H(c2) and T(c)/10(3)) of the organic superconductor kappa-(ET)2Cu(NCS)(2), where quantum fluctuations are expected to dominate thermal effects. Over most of the field range below the irreversibility line ( B(irr)), magnetothermal instabilities are observed in the form of flux jumps. The abrupt cessation of these instabilities just below B(irr) indicates a quantum melting transition from a quasi-two-dimensional vortex lattice phase to a quantum liquid phase.

Journal Article↗

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).

Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.

Adaptor Proteins, Signal Transducing↗

Biosynthesis of poly-beta-hydroxybutyrate (PHB) is controlled by CydR (Fnr) in the obligate aerobe Azotobacter vinelandii.

CydR is an Fnr-like protein in the obligatory aerobic nitrogen-fixing bacterium Azotobacter vinelandii. The cydR mutant overproduces the cytochrome bd terminal oxidase. Using two-dimensional polyacrylamide gel electrophoresis, we showed that beta-ketothiolase and acetoacetyl-CoA reductase were also overexpressed in the cydR mutant. Fumarase C and a coenzyme A transferase, possibly succinyl-SCoA transferase, were decreased in this mutant. Enzyme assays confirmed the elevated beta-ketothiolase and acetoacetyl-CoA reductase activities in this mutant. The cydR mutant accumulated poly-beta-hydroxybutyrate throughout the exponential growth phase, unlike the wild-type strain that only accumulated poly-beta-hydroxybutyrate during stationary phase. The results demonstrate that CydR controls poly-beta-hydroxybutyrate synthesis in A. vinelandii.

Azotobacter vinelandii↗

Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.

The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization. RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice, dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.

Adolescent↗

Efficacy of a psychoeducational intervention in improving relatives' knowledge about schizophrenia and reducing rehospitalisation.

We sought to establish if a brief psychoeducational intervention for relatives is effective in improving relatives' knowledge about schizophrenia and reducing rehospitalization. We evaluated 101 relatives of 55 patients with schizophrenia before and after an 8-week psychoeducational group using a self-report method. We also conducted a matched case-control study of the effects on rehospitalisation for 28 of these patients. We calculated the number of hospital days for each index case and control in the 1 and 2 years before and after the intervention. Relatives made significant gains in their knowledge about schizophrenia, particularly about medication. Patients whose relatives attended the group had significantly fewer days in hospital and days per admission compared to controls in the year after the programme but the effect waned in the second year after the intervention. Controls were almost four times more likely to be readmitted at 2 years than cases. Median time to readmission was significantly longer in cases compared to controls. We conclude that a psychoeducational group, which is valued by carers, is effective in increasing their knowledge about schizophrenia as well as reducing and forestalling the rehospitalization of their affected relatives. Such programmes deliver what carers frequently request in a cost-effective manner.

Adult↗

Induced mood and persistence at gaming.

AIMS: Using the affect infusion model (AIM), this study aimed to assess the impact of prior mood on gaming persistence in regular and non-regular gamblers (assumed to be motivated and heuristic decision-makers, respectively). DESIGN, MEASURES AND SETTING: A 2 x 3 experimental design in a laboratory setting employed factors of gambler type (regular, non-regular) and prior mood (happy, neutral, depressed). Measures were number of trials played on a gambling game, and mood ratings (post-mood induction, during and after play). PARTICIPANTS AND INTERVENTIONS: Sixty regular and 60 non-regular gamblers (all male students) were assigned randomly to watch a video inducing one of the three mood conditions. They were then given AUD$10.00 to gamble in a computerized card-cutting game. FINDINGS: AIM predictions were supported: prior mood did not affect gaming persistence for regular gamblers, but non-regulars showed reduced persistence across happy, neutral and depressed moods. After-play mood ratings were related to winnings for regulars, and losing regulars were significantly more unhappy after-play compared to during-play, and compared to both their winning counterparts and non-regulars. Mood and winnings were unrelated for non-regulars, with little during- to after-play mood change. CONCLUSIONS: The findings speak to depression as a causal factor in addictive gambling. Depressed mood did not enhance persistence in regular gamblers, but rather failed to have the inhibitory effect observed in non-regular gamblers. Evidence of mood changes during gambling was obtained, although multiple measures (self-report, physiological indicators, anticipated states) of both affective valence and arousal are advocated for future studies.

Adult↗

The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease.

OBJECTIVE: To assess the long-term systemic and neurologic responses to enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease. STUDY DESIGN: Patients with type 3 Gaucher's disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective study. Enzyme dose was adjusted to control systemic manifestations. Clinical and laboratory evaluations were performed at baseline and every 6 to 12 months thereafter. Patients were followed up for 2 to 8 years. RESULTS: Significant improvement in hemoglobin levels, platelet count, and acid phosphatase values occurred. Liver and spleen volume markedly decreased, and bone structure improved. Nineteen patients had asymptomatic interstitial lung disease unresponsive to ERT. Supranuclear gaze palsy remained stable in 19 patients, worsened in one patient, and improved in one. Cognitive function remained unchanged or improved over time in 13 patients but decreased in 8 patients, 3 of whom developed progressive myoclonic encephalopathy accompanied by cranial magnetic resonance imaging and electroencephalographic deterioration. CONCLUSIONS: At relatively high doses, ERT reverses almost all the systemic manifestations in patients with type 3 Gaucher's disease. Most treated patients do not deteriorate neurologically. Novel therapeutic strategies are required to reverse the pulmonary and neuronopathic aspects of the disease.

Adolescent↗

The effectiveness of CAHPS among women enrolling in Medicaid managed care.

The large-scale transition of public health insurance programs to managed care has shifted much of the responsibility for selecting appropriate coverage to beneficiaries--a role for which many have had little preparation. This study evaluates the impact of a CAHPS (Consumer Assessment of Health Plans Study) health care report card in assisting newly enrolled Medicaid case heads in selecting a managed care plan. The major finding is that the CAHPS report card helped consumers make more informed decisions. Those who received the report cards found judging quality between plans easier, felt that they had significantly more information on which to make decisions, and recognized the importance of their decision more often than those receiving only standard enrollment packets.

Adult↗