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Biomedical subjects

J Mason

Publications and source records attributed to J Mason.

At least 109 records · Page 6Linked to original sources
PubMed1998

The dilemma of new drugs. Are costs rising faster than effectiveness?

This century has seen a phenomenal growth in the development, understanding and use of pharmaceuticals. Additionally, this period has seen the balance of the treatment needs of patients shift dramatically from infectious to cardiovascular and cancer diseases, and from infancy and middle-age to old age. The value of modern pharmaceuticals to society is undoubted. However, the benefits in terms of health gain, when adequately evaluated, are often more modest than first supposed, and are often achieved at considerable costs and sometimes considerable risks to patients. Data are seldom adequate to attempt a robust evaluation of the cost effectiveness of drugs and compare how cost effectiveness may have changed over time. Rapid increases in development costs coupled with the increasing focus on chronic and old-age diseases make it probable that the cost effectiveness of new drugs is broadly declining, but such a conclusion should be interpreted with caution. The big challenge for the next century with its likely genetic and biotechnological discoveries, bringing as yet unforeseen benefits, risks and costs, is to radically improve the manner in which new drugs are evaluated and diffuse into health systems.

Drug Approval↗
PubMed1997

Relationships between hormonal profile and novelty seeking in combat-related posttraumatic stress disorder.

This study examines relationships between hormonal levels and novelty seeking in a group of 27 Vietnam veterans with combat-related posttraumatic stress disorder (PTSD). Novelty seeking in the veteran sample, measured by the Cloninger Tridimensional Personality Questionnaire (TPQ), was almost twice as high as previously published norms. A distinctive pattern of significant positive correlations was found between novelty seeking scores and serum total triiodothyronine (T3), free T3, the T3/free thyroxine (FT4) ratio, urinary norepinephrine and the norepinephrine/cortisol ratio, while a negative correlation was found between novelty seeking scores and urinary cortisol levels. The findings were confirmed by t test analyses of high vs low novelty seeking subgroups and do not appear to be related simply to the severity of PTSD. These preliminary findings indicate the need to include measures of characterological traits in psychoendocrine studies of PTSD and to investigate their possible usefulness in subtyping this disorder.

Adult↗
PubMed1997

Identification of a ferritin light chain pseudogene near the glycerol kinase locus in Xp21 by cDNA amplification for identification of genomic expressed sequences.

We used cDNA amplification for identification of genomic expressed sequences (CAIGES) to identify genes in the glycerol kinase region of the human X chromosome. During these investigations we identified the sequence for a ferritin light chain (FTL) pseudogene in this portion of Xp21. A human liver cDNA library was amplified by vector primers, labeled, and hybridized to Southern blots of EcoRI-digested human genomic DNA from cosmids isolated from yeast artificial chromosomes in the glycerol kinase region of Xp21. A 3.1-kb restriction fragment hybridized with the cDNA library, was subcloned and sequenced, and a 440-bp intronless sequence was found with strong similarity to the FTL coding sequence. Therefore, the FTL pseudogene that had been mapped previously to Xp22.3-21.2 was localized specifically to the glycerol kinase region. The CAIGES method permits rapid screening of genomic material and will identify genomic sequences with similarities to genes expressed in the cDNA library used to probe the cloned genomic DNA, including pseudogenes.

Base Sequence↗
PubMed1997

Biotechnology: a special case for health technology assessment?

Many substances produced naturally in a wide range of living organisms have been identified to be of benefit in the treatment of human disease. Current health biotechnologies recreate DNA-recombinant cellular processes in laboratory settings to produce 'natural' therapeutics: these are potentially a step forward from traditional pharmacology which has developed synthetic analogues or sought to extract products from donor material. However, with increasing financial pressures, decision makers require evidence that the benefits of biotechnologies justify their costs. The challenges experienced when evaluating the cost-effectiveness of biotechnologies are explored with reference to three examples: HA-1A human monoclonal antibody, erythropoietin and DNase. Difficulties in economic evaluation are similar to those experienced with conventional pharmaceuticals: use of short-term clinical endpoints rather than meaningful health outcomes, the artificial nature of clinical trial protocols, and uncertainty about the applicability of economic data. However, early clinical and economic assessments are required by decision-makers, particularly where biotechnology products fill major gaps in therapy. The financial structure of biotechnology companies may limit movement towards adequate clinical and economic research for health technology assessment. Governments should negotiate with the industry to promote more relevant studies, and develop policies for the managed introduction of products as evidence on effectiveness and cost expands. New technologies often present additional costs requiring reallocation of existing resources. Careful resource planning is required so that cost-effective innovation are not denied to patients.

Antibodies, Monoclonal↗
PubMed1997

Efficacy and safety of fexofenadine hydrochloride for treatment of seasonal allergic rhinitis.

BACKGROUND: H1-receptor antagonists are effective for the treatment of seasonal allergic rhinitis. In rare circumstances, some second-generation H1-receptor antagonists have been associated with prolongation of the corrected QT interval (QTc), thus increasing the risk of ventricular arrhythmias. Fexofendine HCl, the carboxylic acid metabolite of terfenadine, is a new second-generation antihistamine that is nonsedating and does not cause electrocardiographic effects. OBJECTIVE: To investigate the clinical efficacy and safety of fexofenadine HCl in the treatment of ragweed seasonal allergic rhinitis and to characterize the dose-response relationship of fexofenadine HCl at dosages of 60, 120, and 240 mg bid. METHODS: A multicenter, 14-day, placebo-controlled, double-blind trial was conducted with patients suffering from moderate to severe ragweed seasonal allergic rhinitis who met symptom severity criteria after a 3-day placebo baseline period. Patients with minimal or very severe symptoms during the baseline period were excluded. Patients were randomized to receive fexofenadine HCl (60, 120, or 240 mg bid) or placebo at 12-hour dosing intervals (7:00 AM and 7:00 PM). The primary efficacy measure was patient-assessed 12-hour reflective total symptom score before the evening dose (trough). RESULTS: Five hundred seventy patients completed the trial. Fexofenadine HCl at each dosage provided significant improvement in total symptom score (P < or = .003) and in all individual nasal symptoms compared with placebo. The frequency of adverse events was similar among fexofenadine HCl and placebo groups, with no dose-related trends. No sedative effects or electrocardiographic abnormalities, including prolongations in QTc were detected. CONCLUSIONS: Fexofenadine HCl is both effective and safe for the treatment of ragweed seasonal allergic rhinitis. Because there was no additional efficacy at higher dosages, 60 mg bid appears to be the optimal therapeutic dosage for these patients.

Adolescent↗
PubMed1997

Onset of action, efficacy, and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit.

BACKGROUND: Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadine's anti-allergic properties require confirmation in a clinical setting. OBJECTIVE: The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. METHODS: One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the environmental exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33) or placebo (33), after 60 minutes of allergen exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. RESULTS: Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo (P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. CONCLUSIONS: Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen exposure in an environmental exposure unit.

Adolescent↗
PubMed1997

An all oral antiemetic regimen for patients undergoing high-dose chemotherapy with peripheral blood stem cell transplant.

The purpose of the study was to assess the toxicity and efficacy of an oral, combination antiemetic regimen including granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) in the setting of highly emetogenic conditioning chemotherapy for stem cell transplantation. Antiemetic prophylaxis consisted of oral granisetron 2 mg once daily, oral prochlorperazine 10 mg q 6 h and oral dexamethasone 4 mg q 6 h, beginning 1 h prior to chemotherapy on each of the 4 days of chemotherapy and continuing until 24 h after the completion of high-dose chemotherapy (HDC). Patients received either CVP (cyclophosphamide 6 g/m2, VP-16 1800 mg/m2 and carboplatin 1200 mg/m2) or CTP (thiotepa 500 mg/m2 in place of VP-16) in four daily doses given over 4 h from days -4 to -1. Previously mobilized and cryopreserved peripheral blood stem cells (PBSC) were reinfused on day +1. Evaluation of nausea, emetic episodes (EE), adverse events, and rescue medications were recorded on a daily patient diary. Thirty-six patients were entered. Fifty-three percent (95% CI = 37-75%) of patients achieved complete response for emesis (CR = 0 EE/24 h) and 75% (95% CI = 58-90%) had combined complete and major response (CR+MR = 0-3 EE/24 h) during all 5 of the treatment days. During the 5 study days, the average number of patient-days with no emesis was 3.7 (74%) and with 1-3 EE was 4.3 (86%). On days -4, -3, -2, -1 and 0, the combined CR+MR rate for emesis was 97, 92, 86, 78 and 75%, respectively. Nausea was absent or mild on all 5 study days in 57% (95% CI = 37-75%). Eight patients had severe late-onset emesis occurring on days +1 to +3 after reinfusion of stem cells. No clinically significant toxicities attributable to the antiemetic regimen were observed. An all oral antiemetic regimen of granisetron, prochlorperazine and dexamethasone appears to be safe and highly effective in patients receiving multiple, daily, high-dose chemotherapy regimens. This regimen offers the advantage of cost-savings, a low side-effect profile and ease of administration in the predominately outpatient setting of HDC with peripheral blood stem cell transplant (PBSCT).

Administration, Oral↗
PubMed1997

Stanford-Kaiser Permanente G1 study for clinical stage I to IIA Hodgkin's disease: subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation.

PURPOSE: We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD. PATIENTS AND METHODS: Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients. RESULTS: With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy. CONCLUSION: Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD.

Adult↗
PubMed1997

The generalisability of pharmacoeconomic studies.

Authors of pharmacoeconomic analyses understandably want their findings to apply as broadly as possible. Also, decision-makers may have to interpret the results of analyses conducted in healthcare settings other than their own. The validity of transferring or generalising results from one setting to another raises important issues for health-economic evaluation. Pharmacoeconomic analyses attempt to model the costs and benefits of alternative treatments in normal clinical practice. Usually, no single clinical study directly provides all the required information, and a variety of data sources is generally included in each analysis. Different data sources present different problems in terms of their relevance to decision-makers. At one extreme, an analysis based purely on trial outcomes and resource use may be precise, but not reflect normal practice; at the other extreme, an analysis using practice data may appear relevant, but be exposed to biases and confounding. Reviews of published studies suggest that general standards have been inadequate in the past. Reapplying such analyses in different localities may simply replicate inadequate findings. The 'perfect' should not become the enemy of the merely 'good'. Models can be helpful in decision-making, provided that they accurately communicate uncertainties in modelling and data. Even so, there will be limits to the generalisability of pharmacoeconomic models, since the required analysis differs between jurisdictions, and because of variations in normal clinical practice. The transferability of research findings re-opens the issue of credibility in pharmacoeconomics. Methodological standardisation, reporting standards and researcher independence are recognised as important factors for enhancing credibility. Where possible, pharmacoeconomic analyses should reflect the findings of systematic reviews of health outcomes to avoid the risk of biased selection of the evidence. In addition, the application of findings to individual healthcare settings must be considered, since cost effectiveness may vary markedly by setting and perspective.

Decision Support Techniques↗
PubMed1997

Publication bias in clinical trials and economic analyses.

Publication bias is an established notion in the clinical literature; essentially, large studies or positive results are more likely to find their way into the public domain than small studies or negative results. Meta-analysis presents a focus for the problems of publication bias, seeking to summarise the evidence in a particular therapeutic area by retrieving and analysing all available clinical studies. Economic analyses are also vulnerable to publication bias, and at 3 levels: first, in the health-outcomes data available for modelling (resulting from publication bias in the clinical literature); second, in the motivations for conducting an economic analysis; and third, in repeating the process of seeking publication.

Clinical Trials as Topic↗
PubMed1996

Serum triiodothyronine elevation with posttraumatic stress disorder: a cross-cultural study.

This study examines the thyroid hormonal profile in Israeli combat veterans with posttraumatic stress disorder (PTSD) and compares it with the previously reported profile in American Vietnam combat veterans with PTSD. Eleven male combat veterans with PTSD were compared with 11 normal subjects. Thyroid junction was evaluated by the measurement of serum total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH). The mean total T3 level in the Israeli PTSD patients (160.5 ng/dL) was significantly elevated (t = 2.53, p < .02) above that of the comparison group (135.5 ng/dL). Total T3 mean levels were not significantly different between the Israeli PTSD group and two American PTSD groups, but all three PTSD groups had significantly higher total T3 levels than both Israeli and American comparison groups. This preliminary study indicates that T3 elevation in combat-related PTSD may extend across cultures and suggests that further comparison of Israeli and American PTSD and normal groups may be useful in evaluating the significance and implications of the unusual alterations in the thyroid system in PTSD.

Adult↗
PubMed1996

Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

The gene responsible for X-linked adrenal hypoplasia congenita, DAX1, encodes a member of the nuclear hormone receptor superfamily. We sequenced 8851 bp that contained the DAX1 genomic region. The DAX gene was composed of two exons and one 3.4-kilobase intron. Putative TATA and GC boxes and a putative steroidogenic factor 1 response element were present in the 5'-flanking region. Two potentially polymorphic short tandem repeats were identified. The first exon encoded two putative novel zinc finger motifs within a putative DNA binding domain and part of the ligand binding domain, and the second exon encoded the remainder of the ligand binding domain. Although the putative DNA binding domain of DAX1 does not contain substantial sequence similarity to other nuclear hormone receptor superfamily members, the putative ligand binding domain had remarkable similarity to other family members. Single-strand conformational polymorphism analysis permitted identification of three new mutations in DAX1. In conclusion, single-strand conformational polymorphism analysis facilitates identification of mutations in the DAX1 gene, and the short tandem repeats may permit linkage analysis in families in which mutations are not yet identified. We speculate that DAX1 may be the most primitive member of the nuclear hormone receptor superfamily identified in mammals.

Adrenal Insufficiency↗
PubMed1996

Optometrist screening for diabetic retinopathy: evidence and environment.

A recent English government-funded study has suggested that optometrists are not best suited to screening for diabetic retinopathy. This is surprising given the level of training of optometrists and their aptitude in detecting other conditions such as glaucoma and cataract. The need to screen for diabetic retinopathy is discussed. The major unresolved issue concerns the choice of screening modality, i.e. who should perform screening, when and how. A literature search is reported. Given the available evidence, to make conclusions about the relative performance of optometrists with other screeners would be inappropriate. Unresolved controversies could be addressed by new prospective studies of optometrists, and others, in screening. A pragmatic design, mirroring the current environment of care, may be important. In particular, the manner in which diabetics currently present to the health service would make screening by one modality of limited use. If thoughtfully applied, shared care concepts may achieve a broader coverage of patients with diabetics mellitus. Smaller trials investigating sub-issues, and surveys of patients and potential screeners may produce a valuable backdrop in designing appropriate studies. Issues for the development of screening schemes are considered, including the role of training, the development of protocols for care and sharing data, reimbursement and audit.

Cost-Benefit Analysis↗
PubMed1995

Successful laparoscopic repair of paraesophageal hernia.

OBJECTIVE: To evaluate prospectively the safety and efficacy of laparoscopic surgical techniques in the repair of types II and III paraesophageal hernias. DESIGN: Case series. SETTING: Tertiary-care, university-affiliated hospitals. PATIENTS: Twelve consecutive patients undergoing elective laparoscopic repair of type II or type III paraesophageal hernias. Patients were available for follow-up for 1 to 17 months postoperatively. INTERVENTIONS: All patients underwent laparoscopic paraesophageal hernia reduction and repair. Eight patients with gastroesophageal reflux disease underwent concurrent laparoscopic Nissen fundoplication. MAIN OUTCOME MEASURES: Operative times, operative complications, and estimated blood loss were recorded. Postoperative outcome measurements included length of hospital stay, postoperative complications, postoperative gastrointestinal tract symptoms, and patient satisfaction. RESULTS: All patients had successful completion of paraesophageal hernia repair laparoscopically with no recurrences, and with an overall minor morbidity rate of 25%, major morbidity rate of 8%, and no deaths. Eight of 12 patients with concomitant reflux disease underwent successful laparoscopic Nissen fundoplication with complete control of reflux symptoms. The average hospital stay for patients with uncomplicated courses was 2.5 days. Long-term (> 6 weeks) postfundoplication symptoms occurred in 13% of those patients who underwent fundoplication. Eleven (92%) of 12 patients described good to excellent results with complete or near complete control of all preoperative symptoms. CONCLUSIONS: Laparoscopic repair of types II and III paraesophageal hernias can be performed under elective circumstances by experienced laparoscopic surgeons, with acceptable morbidity and comparable short-term efficacy. Addition of a concomitant antireflux procedure should be reserved for those patients with clear preoperative evidence of reflux disease secondary to a mechanically defective lower esophageal sphincter. Patients with a normal lower esophageal antireflux barrier do not need a concomitant antireflux procedure.

Adult↗