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K Abrams

Publications and source records attributed to K Abrams.

At least 55 records · Page 3Linked to original sources
PubMed1996

A new decision model for cost-utility comparisons of chemotherapy in recurrent metastatic breast cancer.

In the absence of comparative clinical and pharmacoeconomic trial data for docetaxel versus paclitaxel as second-line therapy for patients with anthracycline-resistant metastatic breast cancer, a computer-based decision-analysis model was designed to evaluate the comparative utility to patients of these two taxoids. The model used the Markov process to analyse disease states (response, stable disease, progressive disease) and toxicities (acute, cumulative) for each treatment during the period from commencement of up to six 3-weekly cycles of chemotherapy, to death. A cost-utility analysis was carried out using the model, with a probability, a cost and a utility determined for each health state. Response rates were obtained from clinical trial data supplemented by expert clinical opinion. Costs were taken from UK national databases and published sources and the published UK prices of docetaxel and paclitaxel. Utilities for the various health states were established by use of standard gamble and visual analogue methods assessed by 30 oncology nurses in the UK who were acting as proxy patients. The results of the model showed that response rate is the key parameter determining the utility and cost utility of treatments for metastatic breast cancer. Although the total per-patient cost associated with docetaxel was marginally higher than that for paclitaxel (8233 pounds vs 8013 pounds), the higher response rate associated with docetaxel produced an improvement in utility to the patient at an incremental healthcare cost that is acceptable according to available defined limits. Sensitivity analyses revealed that, although the model was sensitive to changes in response rate and drug costs, the cost-utility ratio for docetaxel versus paclitaxel varied within acceptable limits in response to all likely changes in key parameters. In summary, in the base case used in this model, docetaxel produces a substantially larger utility benefit than paclitaxel, at a small additional cost per QALY gained (equivalent to 7 pounds per additional day of perfect health).

Breast Neoplasms↗
PubMed1995

Thrombocytopenia in dogs induced by granulocyte-macrophage colony-stimulating factor: increased destruction of circulating platelets.

Administration of recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) to normal dogs in previous studies induced an increase in peripheral blood neutrophils and a dose-dependent decrease in platelet counts. In six dogs that received the highest tested dose of rcGM-CSF (50 micrograms/kg/d) for a minimum of 12 days, the mean nadir of the platelet count was 46,000/microL (range, 4,000 to 91,000/microL) on day 9 +/- 1.1 after starting therapy, compared with a mean baseline platelet count of 398,000/microL (range, 240,000 to 555,000/microL). In three dogs, survival of autologous 111In-labeled platelets was reduced from a mean of 4.9 days to 1.3 days during the administration of rcGM-CSF. Biodistribution studies with gamma camera imaging indicated that there was an increase in mean hepatic uptake during the administration of rcGM-CSF, from 15% to 44% of the total injected 111In-labeled platelets at 2 hours, whereas splenic uptake was not significantly changed. In contrast, in two evaluable dogs who were recipients of 111In-labeled platelets from matched allogeneic donors receiving rcGM-CSF, platelet survival was not reduced and no increased hepatic uptake was noted. A third dog became alloimmunized to the matched donor platelets and was not evaluable. Immunohistologic studies of liver and spleen were performed with monoclonal antibodies specific for canine gpIIb/IIIa and P-selectin in dogs treated with rcGM-CSF and compared with untreated controls. On treatment, a marked reduction of platelets in the red pulp of the spleen was evident, and in general, the presence of platelet antigen in the liver was unchanged. Therefore, platelets were not being sequestered, but destroyed in the liver and spleen. The platelet antigens, P-selectin and gpIIb/IIIa, were identified in association with Kupffer cells in the liver, but no difference in the number of distribution of these Kupffer cells was found between controls and rcGM-CSF-treated dogs. In the spleen during rcGM-CSF treatment, most platelet antigens were associated with large mononuclear cells in the marginal zone. During administration of rcGM-CSF, CD1c and CD11c expression was increased on Kupffer cells. Platelet P-selectin expression and binding of leukocytes to circulating platelets were unchanged from baseline studies with rcGM-CSF treatment. In conclusion, during the administration of rcGM-CSF to dogs, a local process in the liver and spleen is induced resulting in thrombocytopenia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities.

OBJECTIVE: To examine the importance of submucous myomas and endometrial polyps before and after menopause and in abnormal withdrawal bleeding on hormone replacement therapy (HRT). METHODS: Between May 1991 and May 1993, women presenting with abnormal withdrawal bleeding on HRT (n = 106), menstrual problems in pre-menopause (n = 92), or postmenopausal bleeding (n = 33) underwent diagnostic outpatient hysteroscopy for the presence of intrauterine structural abnormalities. The findings were compared with a control group of post- and perimenopausal women without bleeding problems (n = 183). RESULTS: When compared with women who had normal uterine cavities, the presence of submucous myomas was associated with a threefold increase in the risk of abnormal menstrual bleeding in premenopausal women (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.77-6.43; P < .001) and a twofold increase in the risk of abnormal withdrawal bleeding in post- and perimenopausal women (OR 2.4, 95% CI 1.25-4.53; P = .004). This did not seem to be related to the number of myomas detected. The frequency of endometrial polyps was not found to be significantly higher in women who had menstrual disorders or abnormal withdrawal bleeding on HRT. Postmenopausal bleeding without hormonal stimulation was not significantly associated with submucous myomas or polyps. CONCLUSION: As increasingly more women request HRT, bleeding problems presenting pre-menopause can no longer be expected to resolve "naturally" after menopause. In the presence of submucous myomas, these women will continue to have a higher risk of abnormal withdrawal bleeding when treated with hormone replacement, whereas endometrial polyps are not associated with an increased bleeding risk. Hysteroscopic assessment of the uterine cavity and subsequent counseling as to the risk of heavy or prolonged bleeding will be helpful in their future management and may improve compliance.

Adult↗
PubMed1994

Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases.

Very few patients with liver metastases from colorectal cancer can be cured. We have investigated whether a treatment to slow the growth of liver metastases, hepatic-artery infusion of floxuridine, improves palliation in this setting. In a randomised study of 100 patients, we compared quality of life and survival in patients who received hepatic-artery infusion of floxuridine and in those who received conventional symptom palliation. 95% of control patient survival time was spent with normal quality-of-life scores, which suggests that the aim of treatment should be to prolong normal-quality survival rather than merely to sustain quality of life. There was a significant prolongation (p = 0.03) in overall survival in floxuridine-treated patients compared with controls (median 405 vs 226 days). There were similar significant prolongations in normal-quality (ie, normal symptom scores) survival for physical symptoms (p = 0.04), anxiety (p = 0.04), and depression (p = 0.04). This survival benefit was associated with significant reductions in metastasis size on computed tomography (p = 0.001) and in serum carcinoembryonic antigen concentration (p = 0.006) in floxuridine-treated patients. There was no evidence of treatment-related hepatotoxicity as assessed by serum aspartate aminotransferase and bilirubin measurements. This is the first demonstration that survival can be prolonged with normal quality of life in patients with colorectal liver metastases. We conclude that hepatic-artery floxuridine infusion can be recommended for suitable patients.

Anxiety↗
PubMed1994

Simple Bayesian analysis in clinical trials: a tutorial.

In this tutorial paper we give a simple Bayesian analysis of data that arise in clinical trials. We consider the case when there are two treatment groups and the response in each group can be assumed to be binomially distributed. We also assume that prior beliefs about the rate parameter in each group can be adequately expressed by a Beta distribution. Using such a model approximate posterior inferences can then be made about the odds ratio between the two groups. We illustrate this methodology by analyzing a randomized trial to assess the benefits of treating patients with carcinoma of the pelvic region (rectum, bladder, colon, cervix) using high-energy fast neutrons as opposed to conventional megavoltage x-rays (photons). In this trial there was prior information about the relative efficacy of neutron therapy based on the beliefs of 10 clinicians. Some of the deficiencies of this simple approach are high-lighted and other approaches to analysis indicated. The paper facilitates practical consideration of a Bayesian approach without the complexities that a fuller analysis necessitates.

Bayes Theorem↗
PubMed1993

Effect of organic solvents on in vitro human skin water barrier function.

Skin barrier disruption caused by organic solvents to human cadaver dermatomed skin was evaluated using an in vitro model system. Resultant changes in transepidermal water loss (TEWL), as measured with an evaporimeter, were recorded after topical application of either acetone, chloroform:methanol 2:1, hexane, hexane:methanol 2:3, or the control, water, for exposure times of 1, 3, 6, and 12 min. The resultant lipid/solvent mixture was removed and analyzed for its lipid content. The ability of the different solvents to induce changes in the skin's barrier function was assessed by comparing pre- to post-solvent exposure TEWL (delta TEWL). When compared to the controls, water and unexposed skin, chloroform:methanol 2:1 caused the greatest significant increase in TEWL, followed by hexane:methanol 2:3. Acetone and hexane showed no difference in TEWL from the controls. Besides solvent, exposure time was a significant independent variable for predicting delta TEWL, and the interaction of the two (exposure time and solvent type together) was the strongest predictor. Lipid analysis of the extracts revealed that all the solvents removed comparable quantities of the surface lipids (triglycerides, wax esters, squalene, cholesterol esters). Stratum lipids--ceramides, free fatty acids, and cholesterol--extracted by chloroform:methanol 2:1 and hexane:methanol 2:3 were comparable and significantly greater than those extracted by acetone and hexane. These two solvents failed, however, to induce comparable changes in TEWL, as chloroform:methanol 2:1 induced a significantly greater delta TEWL than hexane:methanol 2:3. Additionally, no individual lipid class extracted by either chloroform:methanol 2:1 or hexane:methanol 2:3 proved to be a significant or accurate variable for predicting delta TEWL. This suggests that the mechanism by which topical chloroform:methanol 2:1 and hexane:methanol 2:3 exposure induce a delta TEWL involves more than pure lipid extraction.

Adolescent↗
PubMed1992

Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160.

Simian immunodeficiency virus (SIV) is a primate lentivirus related to human immunodeficiency viruses and is an etiologic agent for acquired immunodeficiency syndrome (AIDS)-like diseases in macaques. To date, only inactivated whole virus vaccines have been shown to protect macaques against SIV infection. Protective immunity was elicited by recombinant subunit vaccines. Four Macaca fascicularis were immunized with recombinant vaccinia virus expressing SIVmne gp160 and were boosted with gp160 produced in baculovirus-infected cells. All four animals were protected against an intravenous challenge of the homologous virus at one to nine animal-infectious doses. These results indicate that immunization with viral envelope antigens alone is sufficient to elicit protective immunity against a primate immunodeficiency virus. The combination immunization regimen, similar to one now being evaluated in humans as candidate human immunodeficiency virus (HIV)-1 vaccines, appears to be an effective way to elicit such immune responses.

Animals↗
PubMed1992

Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic and laser Doppler flowmetric study using topical pharmacologic antagonists on irradiated skin.

Normal skin responds acutely to ultraviolet (UV) light exposure with complex inflammatory mechanisms. In the present study UVB irradiation ranging from subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96 mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti-inflammatory agents or vehicle control. The resultant change in erythema (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the UVB-induced vascular reactions in different and dose-dependent ways. Betamethasone-17-valerate and diphenhydramine were most effective at the 24 mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH) content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) > indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease = 21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%) > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2) and the decrease in OH was associated with an increased amount of deoxygenized hemoglobin (DOH). A similar slight venous dilatation was present at acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1991

A time-correlation study of ultraviolet B-induced erythema measured by reflectance spectroscopy and laser Doppler flowmetry.

Ultraviolet B (UVB)-irradiated skin pigmentation was quantified using 2 objective and noninvasive techniques. Ten healthy volunteers were exposed to increasing UVB doses in the interval from 6 mJ/cm2 to 120 mJ/cm2 and the resultant vascular and pigmentary changes were evaluated using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). Measurements were made 0.25 h, 1 h, 4 h, 8 h, 24 h, 72 h and 192 h post-irradiation. Visual scores were determined 24 h post-irradiation. Both RS and LDF revealed an early and rapid erythematous response to UVB irradiation, peaking between 8 h and 24 h, with no single UVB dose showing any significant increase until 4 h post-irradiation. LDF showed a peak increase in blood flow at 8 h post-irradiation for sites with low UVB exposure (less than or equal to 36 mJ/cm2). Doses greater than or equal to 42 mJ/cm2 showed maximal increase at 24 h. After this increase in blood flow, a slow normalization began that was not complete at 192 h post-irradiation at sites exposed to greater than or equal to 60 mJ/cm2. The present RS analysis is able to distinguish between oxygenized (OH) and deoxygenized hemoglobin (DOH). The only significant increase in DOH was found for the averaged 6 mJ/cm2 and 12 mJ/cm2 UVB dose sites 24 h after irradiation. OH peaked 24 h post-irradiation and resolution was still incomplete after 192 h. RS revealed no dose, as did the LDF, below which the vascular response peaked earlier. LDF measures dermal blood flow and RS measures hemoglobin content in the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Characterization of glutathione S-transferase expression in lymphocytes from chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is a disease state which frequently responds to alkylating agent chemotherapy but ultimately becomes refractory through acquired resistance mechanisms. In the present study, we have examined the expression of glutathione S-transferases (GST) in both CLL and normal control lymphocytes, as these enzymes have been implicated in mechanisms of natural and acquired resistance. Lymphocyte GST was purified from samples by high-pressure liquid affinity chromatography, and subunits were identified by two-dimensional gel electrophoresis and immunoblotting by using polyclonal antibodies specific for individual subunits. Analysis of CLL lymphocyte GST activity using the general substrate 1-chloro-2,4-dinitrobenzene showed a statistically significant 2-fold increase in cells from chlorambucil-resistant patients over those from untreated patients and normal individuals. Furthermore, chlorambucil therapy was seen to cause a 1.3- to 1.5-fold elevation of enzyme activity in three previously drug-naive patients. Analysis of GST isozyme subunits indicated that 95% of the CLL patients examined were positive for the pi isozyme, and this appeared quantitatively to be the major isozyme present. The alpha and mu isozymes were also expressed in 63 and 53% of the patients, respectively. Examination of control lymphocytes, as well as separated B- and T-cell subpopulations, yielded similar results. The present study indicates that a high degree of interindividual variation occurs and that the pattern of CLL lymphocyte GST expression differs from that of other tumor tissues. While there were no obvious correlations between the disease state or stage and isozymes expressed, the quantitative increase in GST activity in chlorambucil-resistant CLL patients may be of relevance to the overall resistant phenotype.

Aged↗
PubMed1984

Histologic comparisons of interproximal gingival tissues related to the presence or absence of bleeding.

Interproximal gingival tissues were compared histologically relative to the presence or absence of bleeding after stimulation with a wooden interdental cleaner. Fifteen bleeding and 15 nonbleeding interproximal gingival biopsy specimens were obtained from 30 patients and processed for light microscopic evaluation. Morphometric analysis of tissue components revealed that bleeding areas had a significantly greater per cent of inflamed connective tissue. The inflammatory lesion in the bleeding specimens was primarily in the midinterproximal area. From a diagnostic standpoint, this information provides a rationale for the use of bleeding to detect inflammatory lesions in the midinterproximal region.

Adult↗
PubMedDate not supplied

Early stopping rules--clinical perspectives and ethical considerations.

A clinical trial should only be launched in the presence of equipoise both amongst clinicians responsible for treating the disease and their patients. However, during the period of patient recruitment the chances are that the levels of equipoise will modify. In some cases, where toxicity or inferiority of efficacy are readily demonstrable, the trial needs to be stopped prematurely to prevent harm to patients. In other cases, the degree of equipoise may be increased by the very existence of the trial or from conflicting evidence reported from other studies. By reference to four specific trials it is argued that instead of definitive rules, the decision as to whether recruitment should be continued must be the role of a Data Monitoring Committee which is able to consider and respond to all the available evidence.

Bias↗
PubMedDate not supplied

Anxiety mediates the association between anxiety sensitivity and coping-related drinking motives in alcoholism treatment patients.

Anxiety sensitivity (AS), the tendency to interpret feelings of anxiety as dangerous, is a core dispositional trait in a well articulated and extensively studied cognitive model of proneness to anxiety disorder. In recent years, there has been an increasing body of findings that also links AS to the tendency to use alcohol in general and the tendency to use alcohol as a means of coping with negative affect in particular. We expand on this empirical base by proposing and testing a theoretical model in which anxiety symptoms mediate the association between AS and alcohol use. That is, we propose that AS promotes anxiety symptoms, which, in turn, promote alcohol use aimed at coping with anxiety and other negative affect states. Over a 1-year data collection period, we assessed 82 alcohol-dependent individuals shortly after they began an intensive alcoholism treatment program. Self-reported anxiety symptoms associated with distinct anxiety syndromes were obtained with reference to the month period preceding their entry into the treatment program. Other information, including the presence of withdrawal symptoms, was obtained via interview. We found that syndrome-related anxiety symptoms and Trait Anxiety, but not State Anxiety or withdrawal symptoms, mediated the significant association between AS and the self-reported tendency to use alcohol as a means of controlling anxiety symptoms. Demonstrating a similar pattern of findings, but much less robustly so, were tests of these mediator models using alcohol use aimed at coping with negative affect (vs. coping with anxiety per se) as an outcome. In discussing these findings, we attempt to further develop a coherent model that incorporates AS, anxiety symptoms, and drinking motives. Our findings suggest that these relationships may differ for negative affect not specifically related to anxiety. We also discuss the possible associations of AS to withdrawal symptoms implied by our findings.

Adaptation, Psychological↗
PubMedDate not supplied

Meta-analysis and the synthesis of evidence.

Use of meta-analytical (quantitative overview) techniques is now commonplace in a large range of medical-research contexts, with a rapid rise in its frequency of use being particularly apparent in the last decade. Many methods of meta-analysis have been proposed and used, from crude 'vote-counting' of studies showing significant or nonsignificant results, through methods for combination of effect-size estimates based on fixed- or random-effects models, to general, linear, mixed models and Bayesian methods. The history of meta-analysis and the advantages and disadvantages of various approaches to it are briefly reviewed in this paper, with reference to its application in health-services research and related fields. Broader approaches to the synthesis of evidence in these contexts using conventional multilevel modelling and hierarchical Bayesian models to address the combination of evidence from disparate types of study are then outlined.

Bayes Theorem↗