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Biomedical subjects

B Lyons

Publications and source records attributed to B Lyons.

At least 19 recordsLinked to original sources
PubMed2002

Quality of life in advanced non-small-cell lung cancer: results of a Southwest Oncology Group randomized trial.

PURPOSE: The main purpose of this paper is to present the results of a randomized trial comparing the effects of two chemotherapy regimens on the Quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). Trials in advanced stage disease represent an important treatment context for QOL assessment. A second purpose of this paper is to examine methods for handling the level of missing data commonly observed in the advanced stage disease context. METHODS: Patients were randomized to receive cisplatin plus vinorelbine or carboplatin plus paclitaxel. The QOL of 222 patients was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) prior to randomization; follow-up assessments occurred at 13 and 25 weeks. Three methods were used to analyze the QOL data: (1) cross-sectional analysis of four patient categories (improved, stable, missing, and declined) based on changes in the FACT-L score, (2) a mixed linear model, and (3) a pattern mixture model. The longitudinal analyses addressed two potential data biases. RESULTS: Questionnaire submission rates were 91% at baseline, 68% at 13 weeks, and 47% at 25 weeks. The cross-sectional and mixed linear model analyses did not show significant differences by treatment arm in patient-reported QOL. The pattern mixture model analysis, more appropriate given non-ignorable missing data, also found no statistically significant effect of treatment on patient QOL. CONCLUSION: We present a sensitivity analysis approach with multiple methods for analyzing treatment effects on patient QOL in the presence of substantial, non-ignorable missing data in an advanced stage disease clinical trial. We conclude that the two treatment arms did not differ statistically in their effects on patient QOL over a 25-week treatment period.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Anaesthesia for children with epidermolysis bullosa: a review of 20 years' experience.

BACKGROUND AND OBJECTIVE: Epidermolysis bullosa is a rare, genetically determined disorder characterized by excessive susceptibility of the skin and mucosa to separate from the underlying tissues after mechanical trauma. Patients suffering from this disease may have multiple medical problems, but the risk of anaesthesia is attributed mainly to oropharyngeal involvement; airway management may be hazardous and preservation of mucosa and skin integrity problematical. There is a paucity of data in the literature concerning the perioperative management of children with epidermolysis bullosa. We present our experience of managing 54 general anaesthetics (and two local anaesthetics) over the past 20 years. METHODS: The case notes of 16 children with epidermolysis bullosa were reviewed. The children underwent surgical procedures under local or general anaesthesia over a 20-year period. RESULTS: Fifty-four general and two local anaesthetics were administered for 58 procedures in 10 children (mean age 12.6 years). Surgical procedures included oesophageal dilatation (24), insertion/revision of gastrostomy (16), dental procedures (10), hand surgery (2), skin biopsy (2) and others (4). Anaesthesia was induced by inhalation in 73.4% of patients and the airway was maintained with an endotracheal tube in 64.8%. Monitoring of anaesthesia was performed with pulse oximetry (89%), whereas electrocardiography and non-invasive blood pressure monitoring were used in 16.6% of cases each. The mean duration of anaesthesia was 64 min. Tracheal intubation was difficult in two of the five children who were intubated. Mucocutaneous blistering occurred in three children, otherwise there was no attributable morbidity. CONCLUSION: With maximal skin and mucous membrane protection, anaesthesia in children with epidermolysis bullosa may be undertaken with few sequelae.

Adolescent↗
PubMed2001

Health insurance expansion through states in a pluralistic system.

The United States continues to stand almost alone among developed nations in its lack of universal health care coverage. In this essay, we argue that even though the debate over whether the federal government or states should lead the effort to expand health care coverage under the federal system is relevant in strategizing how to cover the uninsured; the more critical issues stem from the challenge of the mixed and fragmented mode of public-private financing of our pluralistic health care system. We base this argument on (1) an in-depth review of Oregon's and Tennessee's five years of experience with broad coverage reform in the context of the United States health care system and on (2) a more abbreviated review of other state experiences in providing health care coverage. We conclude from our review that when the will exists, states can substantially expand coverage. However, as one moves up the income scale, political support and resources are harder to come by. Further, concerns grow about the interface of public and private coverage, with issues of "crowd out" and other distributional questions dominating the discussion of coverage expansion as policy makers focus less on how to cover people than on how to make sure one kind of coverage doesn't preempt another. Concern for crowd out can then lead to policies that keep out some of the very people policy makers may want to cover. In this context the question whether states or the federal government is more likely to succeed in expanding coverage is eclipsed by the more fundamental challenges raised by pluralism. Neither federal nor state government is likely to be fully successful without first identifying ways of better coordinating public and private activities and resources to provide continuous and affordable coverage.

Health Services Research↗
PubMed2001

Influence of operating conditions and vessel size on oxygen transfer during cellulase production.

The production of low-cost cellulase enzyme is a key step in the development of an enzymatic-based process for conversion of lignocellulosic biomass to ethanol. Although abundant information is available on cellulase production, little of this work has examined oxygen transfer. We investigated oxygen transfer during the growth of Trichoderma reesei, a cellulase-producing microorganism, on soluble and insoluble substrates in vessel sizes from 7 to 9000 L. Oxygen uptake rates and volumetric mass transfer coefficients (kLa) were determined using mass spectroscopy to measure off gas composition. Experimentally measured kLa values were found to compare favorably with a kLa correlation available in the literature for a non-Newtonian fermentation broth during the period of heavy cell growth.

Biomass↗
PubMed2001

Vaccination coverage and physician distribution in the United States, 1997.

BACKGROUND: How many physicians are needed in the United States and how they should be allocated geographically and among specialties has been the subject of intense debate, a debate that has often focused more on costs to third-party payers and government than on benefits to health. Child health is a central aspect of public health, and immunization is one of its most cost-effective and easily measured interventions. OBJECTIVE: To examine the association of immunization rates and delivery characteristics with the distribution of child health physicians in the United States in 1997. DESIGN: Cross-sectional ecological study, using the state as the unit of analysis, immunization rates and delivery characteristics (from the National Immunization Survey) as the main outcome measures, concentration of the principal physician specialties providing routine care to children (pediatric, family, and general physicians from the American Medical Association Masterfile) as the main risk factor, while controlling for demographic and economic factors (from the Bureau of the Census and other sources). RESULTS: Of the 96 689 physicians providing routine care to children, 37% were pediatric, 49% family, and 14% general physicians. Higher rates of vaccination, private sector vaccination, and increased numbers of public and private vaccination sites were all associated with the concentration of pediatricians but not of family or general physicians. The distribution of pediatricians was strongly associated with the distribution of residency positions. CONCLUSIONS: Pediatrician distribution is a strong correlate to immunization rates and delivery characteristics. Opportunities to affect pediatrician distribution may exist with allocation of residency positions.

Child↗
PubMed2001

The safety and effectiveness of the Le Fort I approach to removing central skull base lesions.

The difficulty of gaining access to the central skull base has led to the development of many surgical approaches to this area during the past decade. Yet we believe that the Le Fort I technique, which has been used for almost 140 years in orthognathic surgery, is still an excellent approach to treating anterior skull base lesions. This procedure, which entails the horizontal sectioning of the dentoalveolar maxillary segment, seemed to fall out of favor with otolaryngologists after a few reports of complications surfaced during the past 10 to 15 years. In this article, we report a series of seven patients whom we treated with a Le Fort I approach during a 3-year period for a variety of benign and malignant anterior skull base lesions. We have encountered no significant complications of surgery or recurrence of disease at a maximum postoperative followup of 3 years.

Adult↗
PubMed2000

NOD/LtSz-Rag1null mice: an immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells.

Development of a small animal model for the in vivo study of human immunity and infectious disease remains an important goal, particularly for investigations of HIV vaccine development. NOD/Lt mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation readily support engraftment with high levels of human hematolymphoid cells. However, NOD/LtSz-scid mice are highly radiosensitive, have short life spans, and a small number develop functional lymphocytes with age. To overcome these limitations, we have backcrossed the null allele of the recombination-activating gene (Rag1) for 10 generations onto the NOD/LtSz strain background. Mice deficient in RAG1 activity are unable to initiate V(D)J recombination in Ig and TCR genes and lack functional T and B lymphocytes. NOD/LtSz-Rag1null mice have an increased mean life span compared with NOD/LtSz-scid mice due to a later onset of lymphoma development, are radioresistant, and lack serum Ig throughout life. NOD/LtSz-Rag1null mice were devoid of mature T or B cells. Cytotoxic assays demonstrated low NK cell activity. NOD/LtSz-Rag1null mice supported high levels of engraftment with human lymphoid cells and human hemopoietic stem cells. The engrafted human T cells were readily infected with HIV. Finally, NOD/LtSz-Rag1null recipients of adoptively transferred spleen cells from diabetic NOD/Lt+/+ mice rapidly developed diabetes. These data demonstrate the advantages of NOD/LtSz-Rag1null mice as a radiation and lymphoma-resistant model for long-term analyses of engrafted human hematolymphoid cells or diabetogenic NOD lymphoid cells.

Adoptive Transfer↗
PubMed2000

The status of immunization measurement and feedback in the United States.

BACKGROUND: A large body of scientific and programmatic data has demonstrated that provider measurement and feedback raises immunization coverage. Starting in 1995, Congress required that all states measure childhood immunization coverage in all public clinics, and federal grant guidelines encourage private practice measurements. OBJECTIVES: To determine state immunization measurement rates and examine risk factors for high rates. METHODS: Review of 1997 state reports, with correlation of measurement rates to birth cohort and provider numbers, public/private proportions, and vaccine distribution systems. RESULTS: Of the 9505 public clinics, 48% were measured; 4 states measured all clinics; 29 measured a majority. Measurement rates were highest for Health Department clinics (67%), lower for community/migrant health centers (39%), and lowest for other clinics (22%). Rates were highly correlated among categories of clinics (r>+0.308, P<.03), and the fewer the clinics, the higher the measurement rates (r = -0.351, P =. 01), but other factors were not significant. Of the 41,378 private practices, 6% were measured; no state measured all its practices; 1 measured a majority. Private practice measurement rates were not correlated to public clinic measurement rates or other factors examined. Of the 50,883 total providers, 14% were measured; no state measured all providers; 2 measured a majority. A trend toward higher measurement rates was found in states with fewer providers (r = -0. 266, P =.06). CONCLUSIONS: Three years after the congressional mandate, only a minority of public clinics and very few private practices had their immunization coverage measured. Greater efforts will be needed to assure implementation of the intervention. Arch Pediatr Adolesc Med. 2000;154:832-836

Child↗
PubMed2000

Oil and water? Lessons from Maryland's effort to protect safety net providers in moving to Medicaid managed care.

Studies have highlighted the tensions that can arise between Medicaid managed care organizations and safety net providers. This article seeks to identify what other states can learn from Maryland's effort to include protections for safety net providers in its Medicaid managed care program--HealthChoice. Under HealthChoice, traditional provider systems can sponsor managed care organizations, historical providers are assured of having a role, patients can self-refer and have open access to certain public health providers, and capitation rates are risk adjusted through the use of adjusted clinical groups and claims data. The article is based on a week-long site visit to Maryland in fall 1998 that was one part of a seven-state study. Maryland's experience suggests that states have much to gain in the way of "good" public policy by considering the impact of their Medicaid managed care programs on the safety net, but states should not underestimate the challenges involved in balancing the need to protect the safety net with the need to contain costs and minimize the administrative burden on providers. No amount of protection can compensate for a poorly designed or implemented program. As the health care environment continues to change, so may the need for and the types of protections change. It also may be most difficult to guarantee adequate protections to those who need it most--among relatively financially insecure providers that have a limited management infrastructure and that depend heavily on Medicaid and the state for funds to care for the uninsured.

Community Participation↗
PubMed2000

Radiation with concurrent late chemotherapy intensification ('chemoboost') for locally advanced head and neck cancer.

The aim of this study was to review our experience with a treatment regimen that combined conventionally fractionated radiation therapy (70 Gy over 7 weeks) with chemotherapy (cisplatin and fluorouracil), given concurrently in the last 2 weeks of radiation therapy in patients with previously untreated advanced squamous cell cancer of the head and neck region.Twenty-eight patients, all but two having UICC stage IV disease, were treated at the Peter MacCallum Cancer Institute between November 1995 and April 1998. Planned chemotherapy consisted initially of continuous infusion at 10 mg/m(2) per day of cisplatin and 400 mg/m(2) per day of fluorouracil on days 1-5 of weeks 6 and 7 of a conventionally fractionated course of radiotherapy. After the first 14 patients, the dose of fluorouracil was reduced to 360 mg/m(2) per day because of acute toxicity.36.8 months), with an estimated 50% surviving at 2 years (CI, 29-71%). Sixteen patients (57%) developed confluent mucositis and 11 (39%) developed patchy mucositis. The median duration of mucositis for these 27 patients was 1.5 months. Seventeen patients (61%) required nutritional support for a median duration of 1.4 months. Fourteen patients (50%) had grade three skin reactions, and 12 (43%) had one or more other significant (Grade 3) toxicities, predominantly infective. Grade 3 late toxicity has been observed in three patients to date (three xerostomia, including one with severe depression), and one patient had chronic ulceration of the oral tongue (grade 4). This chemoradiation regimen achieved an excellent complete response rate and good locoregional control at 2 years in patients with a poor initial prognosis. Acute toxicity was significant but manageable. The regimen offers an alternative to surgery and postoperative radiation therapy in locally advanced head and neck cancer.

Adult↗
PubMed2000

Substituting proxy ratings for patient ratings in cancer clinical trials: an analysis based on a Southwest Oncology Group trial in patients with brain metastases.

In studies of the effect of cancer treatment in the advanced disease setting, researchers have attempted to avoid missing data for quality of life (QOL) assessments by either substituting proxy for patient assessments from the outset or by interspersing proxy measures when patients are unable to respond. Although poor agreement between patient and proxy assessments has been amply demonstrated in the literature, interest in using proxy measures persists. Completion of the Spitzer QL-Index by a small sample of patients with brain metastases and family member proxies provided data for evaluating the ability to substitute proxy for patient QOL assessments. These data cannot address treatment efficacy due to the modest sample size. Rather, the analyses serve to alert researchers to the important distinction (in a clinical trial setting) between agreement and the use of the proxy as a surrogate. We present several methods for evaluating the accuracy of proxy measures and for identifying other sources of error and bias that may vary with time or with treatment arm. Lin's concordance correlation coefficient suggests that proxies are generally a poor substitute for capturing a patient's perspective of his/her QOL. A longitudinal analysis suggests that the use of proxy rather than patient responses could lead to different conclusions concerning radiation therapy's effect on QOL.

Adult↗
PubMed1999

Ceramide increases steroid hormone production in MA-10 Leydig cells.

Ceramide is known to have major roles in the control of cell proliferation, differentiation, and apoptosis. Recent studies also have shown that ceramide affects steroid production by JEG-3 choriocarcinoma cells, acutely dispersed rat Leydig cells, and ovarian granulosa cells, but the mechanism by which this occurs is unknown. Because ceramide induces apoptosis in many different cell types, we hypothesized that ceramide might affect steroidogenesis and/or induce apoptosis in MA-10 murine Leydig cells. To test this, MA-10 cells were incubated with either the water soluble C2-ceramide, (N-acetyl-sphingosine, 0.01-10 cm); bacterial sphingomyelinase (1-100 mU/ml); or C2-dihydroceramide (N-acetyl-sphinganine, 0.1-10 microM). The data show that N-acetyl-sphingosine significantly increased basal (0.87 +/- 0.2 vs. 0.42 +/- 0.09 ng/mg cell protein, P < 0.01) and human chorionic gonadotropin (hCG) stimulated progesterone (P) synthesis (204 +/- 12 vs. 120 +/- 5 ng/mg cell protein, P < 0.001); as did sphingomyelinase (basal P = 0.83 +/- 0.1 ng/mg cell protein, P < 0.01; hCG stimulated P = 173 +/- 7 ng/mg cell protein, P < 0.001). C2-dihydroceramide also increased basal P synthesis but was less effective than ceramide on a molar basis. Neither sphingomyelinase (100 mU/ml) nor ceramide (10 microM) had any effect on cAMP production or human chorionic gonadotropin binding; and neither induced any signs of apoptosis (FragEL DNA fragmentation assay and electron microscopy). Cells incubated with anti-Fas (300 ng/ml) demonstrated DNA fragmentation, nuclear condensation, and frequent apoptotic bodies, but had no change in P synthesis. These data show that ceramide significantly increases MA-10 Leydig cell P synthesis but does not induce apoptosis. The mechanism by which ceramide increases steroid hormone synthesis remains unknown but does not appear to be linked to the induction of apoptosis in MA-10 cells.

Animals↗
PubMed1999

ENT malignancies. What the GP needs to know.

BACKGROUND: The head and neck are sites that are accessible to examination, therefore early detection of cancers in these sites should be simple. OBJECTIVE: This article discusses the commoner malignant tumours encountered in the various head and neck subsites. It gives an overview of the types of tumours that occur and the presenting features which allow us to distinguish them from benign disorders and facilitate much earlier diagnosis. Recent advances in diagnostic imaging and treatment are discussed. DISCUSSION: Improved outcomes for patients with head and neck cancers will occur with earlier detection and community education about risk factors.

Australia↗
PubMed1999

Immunization performance measurement in a changing immunization environment.

OBJECTIVE: The measurement of performance in the delivery of recommended vaccinations for children is used frequently as a marker for quality of care and as an outcome for studies of interventions to improve immunization coverage levels. The critical element of immunization performance measurement is the determination of immunization status. This methodologic review 1) discusses immunization status as a measure of quality of primary care for children, 2) describes immunization status measures used in immunization intervention studies, and 3) examines selected technical issues of immunization status measurement. METHODS AND TOPICS: 1) Description of the characteristics of immunization status measurements obtained by a systematic review of studies published between 1980 and 1997 on interventions to raise immunization coverage, and 2) illustration of technical considerations for immunization status measurement using one local database and one national database of immunization histories. Technical issues for immunization status measurement include 1) the need to use documented immunization histories rather than parental recall to determine immunization status, 2) the need to link records across providers to obtain complete records, 3) the sensitivity of immunization status to missing immunization data, and 4) the potential of measures incorporating combinations of immunizations to underestimate the degree of vaccination in a population. CONCLUSIONS: Immunization performance measurement has many characteristics of a robust quality of care measure, including high acceptance by primary care providers of routine vaccination, association of immunization status with the conduct of other clinical preventive services, agreed-on technical and programmatic standards of care, and legislative requirements for medical record documentation. However, it is not without challenges. Careful attention to technical issues has potential to improve immunization delivery health services research.

Child↗
PubMed1998

Impact of a large-scale immunization initiative in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)

CONTEXT: Inner-city immunization rates have lagged behind those in other areas of the country. OBJECTIVE: To evaluate the impact of an initiative linking immunization with distribution of food vouchers in the inner city. DESIGN: Retrospective analysis of immunization data gathered in 1996 and 1997. SETTING: Nineteen Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) sites serving 30% of the Chicago, III, birth cohort. PARTICIPANTS: A total of 16581 children 24 months old or younger. INTERVENTIONS: Voucher incentives (varying frequency of food voucher issuance based on immunization status) and assessment of immunization status and referral to immunization provider. MAIN OUTCOME MEASURES: Age-appropriate immunization rates and WIC enrollment rates. RESULTS: During the 15-month period of evaluation, immunization rates increased from 56% to 89% at sites performing voucher incentives. The proportion of children needing voucher incentives declined from 51% to 12%. Sites performing assessment and referral, but not providing voucher incentives, showed no evidence of improvement in immunization coverage. No difference was observed in enrollment rates between sites performing voucher incentives and those that did not. CONCLUSION: Applied in a large-scale, programmatic fashion, voucher incentives in WIC can rapidly increase and sustain high childhood immunization rates in an inner-city population.

Chicago↗
PubMed1997

Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans.

BACKGROUND: Inflammatory and coagulation processes are both affected in meningococcaemia. Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality: in survivors, skin grafts, amputation, and end-organ failure are not uncommon. Protein C is a natural anticoagulant and also has important anti-inflammatory activity. We assessed the effects of early replacement therapy with protein-C concentrate together with continuous veno-venous haemodiafiltration and conventional treatment in meningococcaemia. METHODS: 12 patients aged between 3 months and 27 years with meningococcaemia and severe acquired protein-C deficiency (mean 0.20 IU/mL) were studied. All patients had septic shock, widespread purpura, skin necrosis, and disseminated intravascular coagulopathy. After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adjusted daily to keep the plasma concentration between 0.8 and 1.2 IU/mL. 11 patients were given unfractionated intravenous heparin (10-15 IU kg-1 h-1). Nine patients had haemodiafiltration and one had peritoneal dialysis. The Glasgow meningococcal septicaemia prognostic score and the paediatric risk of mortality score predicted a minimum mortality of 80% and 57%, respectively. FINDINGS: No patient died. No adverse reactions to the treatment were seen. Two patients had lower-limb amputations, one of whom had a thrombotic cerebrovascular accident; both patients had received the protein-C concentrate and heparin later than the rest of the group (60 h [16.97] vs 12 h [3.13]). One patient developed chronic renal failure despite receiving protein-C infusion 15 h after admission. INTERPRETATION: The acquired severe deficiency of protein C in meningococcaemia contributes to the pathogenesis of the thrombotic necrotic lesions in the skin and other organs and probably has an important role in the inflammatory response. Protein-C therapy is merely one approach to improve the host response in this syndrome. We suggest that a double-blind, randomised, controlled multicentre trial is needed to confirm our results.

Adolescent↗