Search PubMed⌕ Search

Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 55 records · Page 3Linked to original sources
PubMed2001

Torasemide: a pharmacoeconomic review of its use in chronic heart failure.

UNLABELLED: Torasemide is a loop diuretic used for the treatment of hypertension and for oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy of torasemide in reducing salt and water retention in CHF has been established in double-blind comparative studies against furosemide. Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action. The efficacy of torasemide (in terms of improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight) has been shown in randomised controlled trials and confirmed in large postmarketing studies. In addition, data from postmarketing studies have shown that patients receiving torasemide had significantly reduced hospital admission rates compared with patients receiving furosemide. Pharmacoeconomic assessments of torasemide have focused on its effect in reducing hospitalisation. Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of torasemide treatment, compared with the 6-month period prior to treatment, in a US retrospective study assessing medical and pharmacy claims data. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1,897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1,944.76 to $US470.76 PPPM) of torasemide treatment. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to $US261.18 PPPM after 12 months. Direct comparison of the torasemide and furosemide study groups was not possible because the group receiving torasemide had much higher healthcare resource use at baseline. Compared with furosemide, torasemide was associated with reduced rates of hospital admissions for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis conducted in Germany, a prospective US study of patients enrolled from hospital admissions and a decision-analysis model. As a result, the direct costs of treatment for CHF or cardiovascular diseases for patients treated with torasemide were less than those with furosemide. However, in the US study, there was no statistically significant difference in hospital admissions for all causes and/or in overall direct medical costs, although the study was not powered to show this. In another US study of managed care patients with New York Heart Association (NYHA) class II or III CHF, no difference in clinical or economic outcomes was observed between patients taking torasemide or furosemide; despite the higher acquisition costs for torasemide, total costs were similar for both groups. Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional (NYHA) class of CHF severity in a retrospective German analysis, although this measure is not ideal. This study also evaluated indirect costs (for loss of productivity of employed patients) and resultssuggest torasemide has a favourable effect in reducing days off work compared with furosemide, although the population of employed patients in the study was very small. Torasemide has been shown to improve some measures of quality of life in 2 studies. It was associated with higher quality-of-life scores than furosemide in a 6-month study, but the differences were only significant at month 4. In another study, torasemide significantly improved fatigue, but full study details are yet to be published. CONCLUSIONS: Despite the higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses have shown that torasemide is likely to reduce overall treatment costs of CHF by reducing hospital admissions and readmissions. Torasemide has generally shown clinical and economic advantages over furosemide, although more long term data are needed to confirm these results and to further investigate effects on quality of life. There are limitations to the currently available pharmacoeconomic data, but present data support the use of torasemide as a first-line option for diuretic therapy in patients with CHF presenting with oedema and especially in those patients not achieving relief of symptoms with furosemide.

Chronic Disease↗
PubMed2001

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

UNLABELLED: Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. CONCLUSIONS: Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Bacterial Infections↗
PubMed2001

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

UNLABELLED: Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. CONCLUSIONS: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.

Adult↗
PubMed2000

Selection by indication of potent antiretroviral therapy use in a large cohort of women infected with human immunodeficiency virus.

To characterize selection factors related to therapy initiation, the authors investigated the extent to which key markers of human immunodeficiency virus (HIV) disease severity were associated with initiation of potent antiretroviral therapy (ART). Logistic regression was used to determine the effects of CD4+ cell count and HIV RNA level on potent ART initiation during 6-month periods among 2,059 HIV-infected US women enrolled in the Women's Interagency HIV Study. Low CD4+ counts and high HIV RNA levels were significantly (p < 0.05) associated with initiation of potent ART. During all periods between April 1996 and March 1998, CD4+ counts were more strongly associated with potent ART initiation than HIV RNA levels were; however, during the last period, both were associated (odds ratio per 100 CD4+-count decrease = 1.17, p < 0.01; odds ratio per 1 log10 increase in HIV RNA level = 1.48, p < 0.05). For a CD4+ count of 500 cells/ml and an HIV RNA level of 5,000 copies/ml, the probability of potent ART initiation increased from 0.5% to 16.8% between October 1995-March 1996 and October 1997-March 1998, suggesting earlier initiation of potent ART. Given the documented occurrence of confounding by indication, prospectively collected, time-dependent data on markers of disease progression and therapy use should be considered when making population-level comparisons before and after introduction of potent ART.

Adult↗
PubMed2000

The relationship between virus load response to highly active antiretroviral therapy and change in CD4 cell counts: A report from the Women's interagency HIV study.

The relationship between the pattern of virus load response to highly active antiretroviral therapy (HAART) and CD4 lymphocyte response was assessed in a cohort of 249 human immunodeficiency virus (HIV) type 1-infected women at 3 times: 1 before and 2 after initiation of therapy, with follow-up of 6-12 months. Patients with a durable response to HAART (i.e., >1 log decrease in HIV-1 RNA sustained for the study periods) had a continuous and significant increase in CD4 cell counts over time, whereas those with no response (<0.5 log decrease in HIV-1 RNA) had a slight decline. Patients with a mixed response (initial decrease >1 log, followed by a subsequent decrease <0.5 log) had an increase in CD4 cell count, followed by a plateau. The trend in CD4 cell count differed significantly by response to HAART, with those patients who experienced a durable response having significantly higher CD4 cell counts than others.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women.

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.

Adult↗
PubMed2000

Factors associated with incident self-reported AIDS among women enrolled in the women's interagency HIV study (WIHS). WIHS Collaboratorive Study Group.

We evaluated factors associated with incident self-reported AIDS diagnoses among HIV-infected women in the Women's Interagency HIV Study (WIHS). Baseline information included age, race/ethnicity, HIV risk category, site of enrollment, years of education, cigarette smoking, CD4 cell count, and HIV viral load. Baseline and follow-up data on self-reported AIDS were analyzed using chi-square, Kaplan-Meier, and Cox proportional hazard models. Among the 1397 HIV-infected women who reported being free of clinical AIDS at baseline, 335 women (24%) reported an incident AIDS diagnosis during follow-up. In stratified Kaplan-Meier analyses, the development of self-reported AIDS was significantly associated with baseline CD4 cell count and viral load (p<0.01). In multivariate Cox proportional hazard analyses, women were statistically more likely to report AIDS if they had CD4 cell counts below 195 cells/mm3 (p<0.01), HIV RNA >4000 copies/ml (p<0.01), were current smokers (p<0.01), and had "no identifiable risk" for acquisition of HIV (p = 0.03). Self-reports of a clinical AIDS diagnosis may not always be accurate, but laboratory markers of HIV disease indicate that those women who self-report such diagnoses have greater immunodeficiency and a higher viral load when compared with those who report no AIDS-defining diagnoses.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Disruption of the gene encoding SF-1 alters the distribution of hypothalamic neuronal phenotypes.

The ventromedial nucleus of the hypothalamus (VMH) in mice first emerges as a histologically distinct cell cluster around embryonic day 17 (E17). The earliest known marker for cells destined to form the VMH is the orphan nuclear receptor, steroidogenic factor 1 (SF-1), which can be detected in the hypothalamic primordium by E11. Strikingly, the VMH is absent in newborn SF-1 knockout mice, suggesting that SF-1 is essential for the development of VMH neurons. We reported previously that the VMH can be identified before it emerges as a histologically distinct nucleus (i.e., at E13) by the exclusion of cells that are immunoreactive for both gamma-aminobutyric acid (GABA) and the synthetic enzyme, glutamic acid decarboxylase (GAD67). Subsequently, by E15, the developing VMH is demarcated further by cells that are immunoreactive for neuropeptide Y, estrogen receptor alpha (ERalpha), and galanin. It is noteworthy that the normal exclusion of GABA from the developing VMH is not seen in SF-1 knockout mice, and cells that are immunoreactive for neuropeptide Y, ERalpha, and galanin also are distributed aberrantly in this region. Thus, the absence of SF-1 profoundly affects the cellular architecture of the VMH from early stages in its formation. These data suggest that, directly or indirectly, SF-1 plays important roles in determining the distribution of cells in the mediobasal hypothalamus.

Animals↗
PubMed2000

Association of race and gender with HIV-1 RNA levels and immunologic progression.

CONTEXT: HIV-1 RNA and lymphocyte subset levels are the principal indications for antiretroviral treatment. Past reports have differed with regard to the effect of gender and race on these measures and in measures of disease progression. OBJECTIVE: To assess racial and gender differences in HIV-1 RNA levels and CD4+ lymphocyte decline. DESIGN: A longitudinal study based in the two largest HIV natural history cohort studies conducted in 7 metropolitan areas of the United States. RESULTS: In all, 1256 adult women and 1603 adult men for whom multiple data points were available prior to initiation of antiretroviral therapy were included. Women were more likely to be nonwhite, to have a history of injection drug use, and to have HIV-associated symptoms. After adjustment for differences in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200 cells/mm3 (p <.001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels were also 41% lower in nonwhites than in whites (p <.001) and 21% lower in persons reporting a prior history of injection drug use (p <.001). Women had more rapid declines in CD4+ cell counts over time than men (difference in slope of 46 cells/year) and nonwhite individuals had slower decline in CD4 cell counts than whites (difference of 39 cells/year). CONCLUSIONS: Both race and gender influence the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by decline in CD4 cell counts over time. These effects could provide clues regarding the factors that influence HIV-disease progression and may indicate that guidelines for therapy should be adjusted for demographic characteristics.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Single-molecule studies of the effect of template tension on T7 DNA polymerase activity.

T7 DNA polymerase catalyses DNA replication in vitro at rates of more than 100 bases per second and has a 3'-->5' exonuclease (nucleotide removing) activity at a separate active site. This enzyme possesses a 'right hand' shape which is common to most polymerases with fingers, palm and thumb domains. The rate-limiting step for replication is thought to involve a conformational change between an 'open fingers' state in which the active site samples nucleotides, and a 'closed' state in which nucleotide incorporation occurs. DNA polymerase must function as a molecular motor converting chemical energy into mechanical force as it moves over the template. Here we show, using a single-molecule assay based on the differential elasticity of single-stranded and double-stranded DNA, that mechanical force is generated during the rate-limiting step and that the motor can work against a maximum template tension of approximately 34 pN. Estimates of the mechanical and entropic work done by the enzyme show that T7 DNA polymerase organizes two template bases in the polymerization site during each catalytic cycle. We also find a force-induced 100-fold increase in exonucleolysis above 40 pN.

Bacteriophage T7↗
PubMed2000

Examination of intrafascicular muscle fiber terminations: implications for tension delivery in series-fibered muscles.

Mammalian skeletal muscles with long fascicle lengths are predominantly composed of short muscle fibers that terminate midbelly with no direct connection to the muscle origin or insertion. The manner in which these short fibers terminate and transmit tension through the muscle to their tendons is poorly understood. We made an extensive morphological study of a series-fibered muscle, the guinea pig sternomastoid, in order to define the full range of structural specializations for tension transmission from short fibers within this muscle. Terminations were examined in single fibers, teased small bundles of fibers, and in sections at both the light and electron microscopic level. In many cases, sites of fiber termination were defined by reactivity for the enzyme acetylcholinesterase, which also marks myotendinous junctions. Additionally, transport of the lipophilic fluorescent dye, DiI, or injection of Lucifer Yellow were used to visualize undisturbed fiber terminations in whole muscles using confocal and fluorescence microscopy. At the light microscopic level, we find that intrafascicularly terminating fibers end about equally often in either a long progressive taper, or in a series of small or larger blunt steps. Combinations of these two morphologies are also seen. However, when analyzed at higher resolution with confocal or electron microscopy, the apparently smooth progressive tapers appear also to be predominantly composed of a series of fine stepped terminations. Stepwise terminations in most cases join face-to-face with complementary endings of neighboring muscle fibers, some via an extended collagenous bridge and others at close interdigitating myomyonal junctions. These muscle-to-muscle junctions show many of the features of myotendinous junctions, including dense subsarcolemmal plaques in regions of myofibrillar termination and we suggest that they serve to pass tension from fiber to fiber along the longitudinal axis of the muscle. In addition, we observe regions of apparent side-to-side adhesion between neighboring fibers at sites where there is no apparent fiber tapering or structural specialization typical of myofibril termination. These sites show acetylcholinesterase reactivity, and large numbers of collagen fibers passing laterally from fiber to fiber. These latter connections seem most likely to be involved in lateral transmission of tension, either from fiber to fiber, or from fiber to endomysium. Overall, our results suggest that tension from intrafascicularly terminating fibers is likely to be passed along the muscle to the tendon using both in-series and in-parallel arrangements. The results are discussed in light of current theories of tension delivery within the series-fibered muscles typical of large, nonprimate mammals.

Acetylcholinesterase↗
PubMed2000

Driving skills in elderly persons with stroke: comparison of two new assessment options.

OBJECTIVE: To compare the effectiveness of two methods of assessing off-road driving skills that claim to predict on-road driving fitness of persons with stroke. METHOD: Fifty-six persons with stroke (age 44 to 82 yrs; mean, 60.2 yrs) completed the 2 off-road driving assessments along with standard clinical and on-road driving tests. MAIN OUTCOME MEASURES: Linear stepwise regression on 4 variables of the Dynavision Performance Assessment Battery (DPAB), the Cognitive Behavioral Driver's Inventory (CBDI) variable (composite score), and the variables of age, gender, and lesion side. RESULTS: A 4-minute endurance subtest from the DPAB was superior to the CBDI in predicting success/failure in the on-road driving test (75%). However, success on both the 4-minute endurance subtest from the DPAB and the CBDI tests significantly improved the prediction of on-road success. If participants passed the CBDI and the endurance test from the DPAB, they also passed the on-road assessment. CONCLUSION: Driving fitness of elderly persons with stroke can be assessed with reasonable accuracy using off-road tests, minimizing the expense and risk associated with on-road assessments in this population.

Adult↗
PubMed2000

Aldosterone and the heart.

Classically, aldosterone is a steroid hormone secreted from the adrenal cortex, which acts on kidney, colon and sweat/salivary glands to promote unidirectional sodium transport. Currently, there is excellent experimental evidence for aldosterone acting directly on the central nervous system to raise blood pressure, and on the heart to cause cardiac hypertrophy and fibrosis. In addition, there is emerging evidence for aldosterone synthesis in the heart, and for as yet unexplained benefits of aldosterone antagonism in the treatment of cardiac failure.

Aldosterone↗
PubMed2000

Spo0A directly controls the switch from acid to solvent production in solvent-forming clostridia.

The spo0A genes of Clostridium beijerinckii NCIMB 8052 and Clostridium cellulolyticum ATCC 35319 were isolated and characterized. The C-terminal DNA-binding domains of the predicted products of spo0A from these two organisms, as well as 16 other taxonomically diverse species of Bacillus and Clostridium, show extensive amino acid sequence conservation (56% identity, 65% similarity over 104 residues). A 12-amino-acid motif (SRVERAIRHAIE) that forms the putative DNA recognition helix is particularly highly conserved, suggesting a common DNA target. Insertional inactivation of spo0A in C. beijerinckii blocked the formation of solvents (as well as spores and granulose). Sequences resembling Spo0A-binding motifs (TGNCGAA) are found in the promoter regions of several of the genes whose expression is modulated at the onset of solventogenesis in Clostridium acetobutylicum and C. beijerinckii. These include the upregulated adc gene, encoding acetoacetate decarboxylase (EC 4.1.1. 4), and the downregulated ptb gene, encoding phosphotransbutyrylase (EC 2.3.1.c). In vitro gel retardation experiments using C. acetobutylicum adc and C. beijerinckii ptb promoter fragments and recombinant Bacillus subtilis and C. beijerinckii Spo0A suggested that adc and ptb are directly controlled by Spo0A. The binding affinity was reduced when the 0A boxes were destroyed, and enhanced when they were modified to conform precisely to the consensus sequence. In vivo analysis of wild-type and mutagenized promoters transcriptionally fused to the gusA reporter gene in C. beijerinckii validated this hypothesis. Post-exponential phase expression from the mutagenized adc promoter was substantially reduced, whereas expression from the mutagenized ptb promoter was not shut down at the end of exponential growth.

Acids↗
PubMed2000

Transient exotropia after posterior spinal fusion in a child: a new case.

Ocular complications after spinal surgery are rare, although ischemic optic neuropathy, occipital lobe infarcts, and central retinal vein thrombosis have been reported. Our purpose is to report a case of an acute, comitant, postoperative exotropia that rapidly and spontaneously resolved. This case is particularly interesting in that it may indirectly shed some light on mechanisms of vergence control.

Child↗