Biomedical subjects

Alexander M Walker

Publications and source records attributed to Alexander M Walker.

47 records · Page 3Linked to original sources

PubMed2002

Risk analysis for mortality from respiratory tumors in a cohort of refractory ceramic fiber workers.

Although workers in refractory ceramic fibers (RCF) manufacturing facilities have experienced no elevations in lung cancer or mesothelioma rates, the historical experience of asbestos together with animal studies of RCF have led to ongoing studies of the respiratory health of RCF workers. We have compared lung cancer and mesothelioma in the accumulated mortality experience of a cohort of male RCF production workers (Lemasters et al., 2001, submitted for publication) to that which would have been expected if RCF had a carcinogenic potency similar to that of various forms of asbestos. To accomplish this, we used risk models recently formalized by Hodgson and Darnton (2000, Ann. Occup. Hyg. 41, 13-36) for asbestos cohorts together with the RCF exposure measurements and historical reconstructions of Rice and colleagues (1997, Appl. Occup. Environ. Hyg. 12, 54-61). Deaths from lung cancer in the RCF cohort are statistically significantly below that which would be expected if RCF had the potency of either crocidolite or amosite. The mortality is also lower than would be expected if RCF had the potency of chrysotile, but the difference is not statistically significant. For mesothelioma, the anticipated numbers of deaths under hypotheses of asbestos-like potency are too small to be rejected by the zero cases seen in the RCF cohorts. The current epidemiologic studies do not rule out risk, but they clearly do rule out lung cancer risks like those of crocidolite or amosite. The residual uncertainty justifies ongoing workplace surveillance.

Adolescent↗

PubMed2002

Methods and objectives of a large US multicenter case-control study of post-transplant lymphoproliferative disorder in renal transplant patients.

A large multicenter case-control study is in progress in the United States, the primary goal of which is to provide information about the effects of specific immunosuppressants and other risk factors on posttransplant lymphoproliferative disorder (PTLD) in renal transplant patients. It will also provide incidence data and case characterization on PTLDs arising in a large contemporary population. Medical record data are being collected on up to 120 PTLD cases and up to four controls per case transplanted at 20 large US centers. Participants all received transplants on or after July 1, 1995 and PTLD cases will be identified through December 31, 2001. All cases undergo central clinical and pathologic review. Abstracted information includes detailed data (dosages, duration) on all immunosuppressants (induction, maintenance, anti-rejection) as well as antiviral treatment. Other data include demographics, transplant history, HLA matching and viral status (e.g., Epstein-Barr virus, cytomegalovirus). Information associated with the PTLD diagnosis and initial therapy for PTLD is also collected. To date, 86 potential cases have been reported. Twenty (24%) are pediatric patients (< or =18 years). Median time between transplant and PTLD is 268 days; 53 (62%) were diagnosed within the first year. Cumulative incidence through 1998 is 0.7% for adults and 4.5% for children. The most common single site for PTLD is the allograft. Common treatments included either a reduction or discontinuation of immunosuppression (90%) and antiviral treatment (66%). Overall, the allograft appears to be an important site of PTLD recurrence. Also, the incidence of renal PTLD since the introduction of new immunosuppressive therapies is similar to that reported earlier.

Adolescent↗

PubMed2002

Risk for respiratory events in a cohort of patients receiving inhaled zanamivir: a retrospective study.

BACKGROUND: Inhaled zanamivir is indicated for treatment of uncomplicated acute illness due to influenza A and B viruses in patients aged > or = 12 years who have been symptomatic for no more than 2 days. OBJECTIVE: The primary objective of this study was to estimate the incidence of adverse respiratory events among zanamivir-treated patients under conditions of usual care. METHODS: The Ingenix research database includes insurance claims for all dispensations, inpatient and outpatient services, and procedures including the associated diagnoses and costs for a subset of all enrolled UnitedHealthcare members. We identified all persons with a dispensation of zanamivir recorded between October 1, 1999, and April 30, 2000. We captured medical and pharmaceutical claims data for the 6 months before the dispensation to obtain information about comorbidities, overall health status, and respiratory events. Medical and hospital record abstraction and clinical review served to confirm inpatient/emergency department (ED) events. We also examined the records of an approximately 10% random sample of patients treated for a potential respiratory event in an outpatient/ physician office visit during the 10-day follow-up period. Respiratory events not sufficiently severe to result in medical care were not captured in this study. RESULTS: A total of 5498 eligible zanamivir dispensations contributed by 5450 patients (2911 females, 2539 males; mean age, 38.8 years), with 40 confirmed inpatient/ED respiratory events, were included in the study. Of these 40 events, 31 were pneumonia, bronchitis, or exacerbations of existing chronic respiratory disease; none required intubation or ventilation. No events occurred on the dispensation date. The overall risk for an inpatient/ ED respiratory event was 0.7 per 100 episodes (95% CI, 0.5-1.0). Seven events of wheezing or shortness of breath were not an obvious extension of the original influenza-like illness or of a complicating bronchitis (risk = 0.13 per 100 episodes; 95% CI, 0.06-0.26). CONCLUSIONS: No immediate or severe bronchoconstrictive responses occurred among 5498 zanamivir dispensations. The overall risk for any respiratory event was low, and none was sufficiently severe to suggest respiratory failure.

Administration, Inhalation↗

PubMed2002

The effect of zanamivir treatment on influenza complications: a retrospective cohort study.

BACKGROUND: Complications of influenza are a major cause of morbidity and mortality during the influenza season. Clinical trials of zanamivir have reported a reduced incidence of influenza complications among high-risk patients. OBJECTIVES: This retrospective study sought to determine whether the use of zanamivir lowers the risk of acute influenza complications in a broader population, based on an analysis of claims data from a large managed care organization. METHODS: Medical and pharmacy health insurance claims data from October 1, 1999, through April 30, 2000, were compiled for UnitedHealthcare members in 19 states. All patients with a diagnosis of influenza (International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code 487.xx) associated with a physician visit were identified. From these, all patients were selected who had received zanamivir on the same day as the diagnosis of influenza. The propensity score matching technique was used to identify a comparison group with similar health service utilization and comorbidities who received a diagnosis of influenza but no antiviral therapy. Follow-up started the day after the influenza diagnosis and continued for 21 days. RESULTS: From the 43,741 patients originally identified, 2341 were selected who received a simultaneous diagnosis of influenza and a prescription for zanamivir. The untreated comparator group numbered 2337. Fewer zanamivir patients than untreated patients were hospitalized for complications, and the absolute risks were low (0.6% and 1.0%, respectively; risk ratio [RR], 0.58; 95% CI, 0.30-1.12). Zanamivir-treated patients had an excess of outpatient visits (16.9% vs 14.5%; RR, 1.16; 95% CI, 1.02-1.33) and antibiotic use (16.3% vs 14.8%; RR, 1.10; 95% CI, 0.97-1.26), although the RRs were modest. CONCLUSIONS: In the setting of a large managed care plan, patterns of influenza complications were similar in zanamivir-treated and untreated patients with a diagnosis of influenza. The results of this study are in contrast to those of published clinical trials reporting a reduction in the risk of influenza complications in zanamivir-treated patients.

Adolescent↗

PubMed2002

Quasi-experimental longitudinal designs to evaluate drug benefit policy changes with low policy compliance.

A causal relation between drug benefit policy change and the increase in adverse outcomes can be tested by comparing the experience of a group of patients affected by the policy vs. the (counterfactual) experience of the same patients if the policy had not been implemented. Because counterfactual experiences cannot be observed, it must be assumed that the counterfactual is correctly described by extrapolating from the same population's previous experience. The null hypothesis of no policy effect can be empirically tested using quasi-experimental longitudinal designs with repeated measures. If compliance to a policy is low, results may be biased towards the null, but a subgroup analysis of compliers may be biased by nonignorable treatment selection. Using the example of reference drug pricing in British Columbia we discuss assumptions for causal interpretations of such analyses, and provide supplementary analyses to assess and improve the validity of findings. Results from nonrandomized comparisons of subgroups defined by their compliance to a policy change should generally be interpreted cautiously, and several biases should be explored.

Attitude of Health Personnel↗

PubMed2002

Comparison of resource utilization by patients treated with transdermal fentanyl and long-acting oral opioids for nonmalignant pain.

OBJECTIVE: To quantify resource utilization and costs incurred for patients who received transdermal fentanyl as their first long-acting analgesic for non-malignant pain, and to compare these with utilization and costs for similar patients dispensed other long-acting oral opioids. DESIGN: A retrospective matched cohort study using medical claims data from a large New England Insurer. PATIENTS: We identified 478 patients without cancer who received transdermal fentanyl during 1995-1998. We selected patients who had no previous long-acting opioid dispensings and were enrolled during the 180 days before and 30 days following the initial dispensing. We used propensity scores to identify a matched comparison group of 478 long-acting oral opioid users. RESULTS: Transdermal fentanyl and matched long-acting oral opioid users incurred identical median costs for outpatient medical services and prescriptions during 2 years of follow-up. A larger proportion of transdermal fentanyl patients were still taking their initial opioid analgesic at the end of the 2-year follow-up than were patients initially taking other long-acting opioids. Use of short-acting opioids tapered off more slowly among transdermal fentanyl patients than among long-acting opioid patients. In the first 6 months, the transdermal fentanyl patients had more hospital discharges than the long-acting oral opioid patients, but this difference appeared to reflect preexisting conditions. CONCLUSIONS: Users of fentanyl transdermal system and other long-acting opioids experienced essentially identical evolution of health services utilization and costs over a 2-year period. The choice of long-acting opioid analgesia does not appear to be a determinant of future medical costs.

Journal Article↗

PubMed2002

The impact of wording in "Dear doctor" letters and in black box labels.

OBJECTIVES: The Food and Drug Administration and pharmaceutical manufacturers use "Dear doctor" letters to alert physicians about drug safety. To determine how such warnings may be improved, we retrospectively examined how variations in the wording of one series of "Dear doctor" letters affected their impact on concomitant dispensing of cisapride (Propulsid; Janssen Pharmaceutica, Titusville, NJ) and several medications contraindicated for concomitant use. METHODS: Concomitant dispensing was defined as dispensing cisapride and a contraindicated medication on dates when the intended duration of the two dispensings overlapped on at least 1 day. Using outpatient pharmacy claims from a New England health insurer, we calculated a concomitant dispensing rate for each calendar month as the number of concomitant cisapride dispensings divided by the total number of cisapride dispensings. We grouped drugs contraindicated for concomitant use with cisapride as (1) explicitly named in the warnings, (2) only mentioned as examples of a drug class, or (3) only implied as drug class members. We used multivariate analysis to relate temporal changes in concomitant dispensing rates to type of warning (explicit, example, or implied), patient demographic characteristics, season, calendar year, and temporal relationship to the "Dear doctor" warnings. RESULTS: A highly publicized letter sent in June 1998 was associated with a notable decline (58%) in the concomitant dispensing rate with explicitly contraindicated drugs but not in the concomitant dispensing of cisapride with the example or implied drugs. An earlier letter, which had been explicit but was accompanied by less publicity, had no measurable effect on this study's measure of coprescription, nor did a later letter that emphasized comorbidities. CONCLUSIONS: Explicit, well-publicized drug warnings can change prescriber behavior.

Adverse Drug Reaction Reporting Systems↗

PubMed2002

The urban spread of visceral leishmaniasis: clues from spatial analysis.

BACKGROUND: The pattern of spread of visceral leishmaniasis in Brazilian cities is poorly understood. METHODS: We used geographic information systems and spatial statistics to evaluate the distribution of 1061 cases of visceral leishmaniasis in Teresina, Brazil, in 1993 through 1996. RESULTS: A locally weighted (LOESS) regression model, which was fit as a smoothed function of spatial coordinates, demonstrated large-scale variation, with high incidence rates in peripheral neighborhoods that bordered forest land and pastures. Moran's I indicated small-scale variation and clustering up to 300 m, roughly the flight range of the sand fly vector. CONCLUSIONS: Spatial analytical techniques can identify high-risk areas for targeting control interventions.

Brazil↗

PubMedDate not supplied

Precautions for proactive surveillance.

Four barriers confront the architects and users of surveillance systems. Bonferroni's Bind blunts our ability to act on real safety signals when the surveillance scheme is capable of producing realistic but wrong signals just by chance. The paradox of definitive data is that the results of a truly comprehensive scheme become untestable because there is no further relevant information to be had. Flexible priors augment the first two barriers by intensifying our instinctive cautions, and by giving almost any claim the appearance of empiric proof. The poverty of tabular summaries is that they presuppose the existence of relevant categories for tabulation, and that they fail to persuade. The resolution for proactive surveillance is sen/cen: high sensitivity to signals and vigorous censoring to filter out the noise.

Humans↗

PubMedDate not supplied

Severe vascular events in migraine patients.

OBJECTIVE: To estimate rates of vascular events in relation to dispensing of triptans and ergot alkaloids among migraineurs, and to compare these rates with those of nonmigraineurs. CONTEXT: It has been speculated that the use of triptans or ergot alkaloid drugs might increase risk of ischemic events through vasoconstriction. DESIGN: A retrospective cohort study of 130,411 migraineurs and 130,411 age-, sex-, and health plan-matched nonmigraineurs who were members of UnitedHealthcare during 1995 through 1999. The data source for this study was Ingenix's research database containing pharmacy and medical claims for UnitedHealthcare members, and the National Death Index. MAIN OUTCOME MEASURES: Incidence of cardiovascular and cerebrovascular events and mortality. RESULTS: Migraineurs and nonmigraineurs had identical rates of myocardial infarction: 1.4 per 1000 person-years. Migraineurs were 67% more likely to suffer a stroke than nonmigraineurs (adjusted relative risk [RR] 1.67, 95% confidence interval [CI] 1.31-2.13), and had higher rates of unstable angina and transient ischemic attacks. There was no increase in risk of myocardial infarction with current (adjusted RR 0.80, 95% CI 0.58-1.11) or recent (adjusted RR 1.15, 95% CI 0.71-1.87) triptan use. Neither current (adjusted RR 0.90, 95% CI 0.64-1.26) nor recent (adjusted RR 0.84, 95% CI 0.46-1.55) triptan use was associated with risk of stroke. Current users of ergot alkaloids were somewhat more likely to have a stroke than other migraineurs (adjusted RR 1.49, 95% CI 0.93-2.41), but there was no dose-response relationship. CONCLUSIONS: Use of triptans is not associated with increased risk of any ischemic events, including myocardial infarction and stroke, or mortality. Consistent with previous studies, migraineurs in general have an elevated risk of stroke, but not myocardial infarction, compared with nonmigraineurs.

Adult↗

PubMedDate not supplied

Lung cancer and mesothelioma among male automobile mechanics: a review.

BACKGROUND: Extensive, overt asbestos exposure clearly causes lung cancer and mesothelioma. Elevated cancer risk has also been documented for short term or low levels of asbestos exposure. Automobile mechanics are potentially exposed to asbestos through brake repair work. Few studies have specifically examined the risk of lung cancer and mesothelioma associated with exposure to asbestos in brakes, but automobile mechanics are included in many studies of occupation and cancer. METHODS: We critically reviewed all epidemiologic studies of lung cancer and mesothelioma risk among male automobile mechanics identified through a broadly based Medline search and scrutiny of references in primary and review articles. We discuss the studies grouped by study design and control for smoking, the major risk factor for lung cancer. RESULTS/CONCLUSIONS: We reviewed all individual analytical studies meeting our criteria, plus all available case series and case reports. When examined in aggregate, the evidence did not support an increase in risk of either lung cancer or mesothelioma among male automobile mechanics occupationally exposed to asbestos from brake repair.

Asbestos↗