Safety and efficacy outcomes with erythropoiesis-stimulating agents in patients with breast cancer: a meta-analysis.

BACKGROUND: New data on erythropoiesis-stimulating agents (ESAs) regarding overall survival and disease progression-related outcomes in patients with breast cancer receiving chemotherapy are presented in a meta-analysis of controlled trials of ESA use (epoetin α, epoetin ß, darbepoetin α, biosimilars). PATIENTS AND METHODS: A literature search identified reports from January 1997 through March 2014. We used company databases for Amgen, Inc., or Janssen studies and published data for other studies. Random-effects odds ratios (ORs) were calculated to compare results for patients randomized to ESA with those randomized to control. RESULTS: Deaths were reported for 571 of 2346 patients (24%) in the ESA groups and 523 of 2367 patients (22%) in the control groups [OR, 1.20; 95% confidence interval (CI) 1.03-1.40]. Sensitivity analyses were conducted to explore the effects of individual studies and exclusion of one study (BEST) resulted in an OR for death of 1.12 (95% CI 0.94-1.34). In seven studies reporting progression-related end points (N = 4197; ESA n = 2088; control n = 2109), the OR was 1.01 (95% CI 0.87-1.16) for ESA compared with control. CONCLUSIONS: After incorporating recent results of ESA use in patients with breast cancer, risks of survival and progression-free survival remain consistent with previously published data.

Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes.

BACKGROUND: Cancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events. METHODS: This meta-analysis included studies from the 2006 Cochrane meta-analysis, studies published/updated since the 2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of cancer. Data were summarised using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Results indicated that ESA use did not significantly affect mortality (60 studies: OR=1.06; 95% CI: 0.97-1.15) or disease progression (26 studies: OR=1.01; 95% CI: 0.90-1.14), but increased the risk for venous-thromoboembolic events (44 studies: OR=1.48; 95% CI: 1.28-1.72). CONCLUSION: Though this meta-analysis showed no significant effect of ESAs on survival or disease progression, prospectively designed, future randomised clinical trials will further examine the safety and efficacy of ESAs when used according to the revised labelling information.

Darbepoetin alfa in lung cancer patients on chemotherapy: a retrospective comparison of outcomes in patients with mild versus moderate-to-severe anaemia at baseline.

GOALS: Currently, there is some debate concerning the haemoglobin level at which treatment of anaemia with erythropoiesis-stimulating agents should be initiated in cancer patients on chemotherapy. We report several analyses of data from a phase III trial of darbepoetin alfa versus placebo, comparing outcomes for patients with mild and moderate-to-severe anaemia. PATIENTS AND METHODS: Data were obtained from a phase III trial of darbepoetin alfa versus placebo in anaemic patients with lung cancer receiving chemotherapy ( n=314). Outcomes were compared for patients with baseline haemoglobin > or =10-11 g/dl and <10 g/dl. RESULTS: Darbepoetin alfa significantly reduced transfusions compared with placebo, irrespective of haemoglobin level at treatment initiation. For patients with baseline haemoglobin <10 g/dl, 31% and 59% of those receiving darbepoetin alfa and placebo, respectively, required a transfusion from week 5 to the end of the treatment phase ( P<0.038). For patients with baseline haemoglobin > or =10 g/dl, the proportions were 15% and 41%, respectively ( P<0.001). Darbepoetin alfa also improved fatigue compared with placebo in both haemoglobin categories. CONCLUSIONS: These findings show that initiating treatment at haemoglobin levels both <10 g/dl and > or =10-11 g/dl results in substantial clinical benefits, supporting the use of erythropoietic therapy also in patients with mild anaemia.

Mandibular reconstructive surgery in a patient with median cleft of the lower lip and mandible.

A patient 15 years and 11 months of age with median cleft of the lower lip and mandible underwent mandibular reconstructive surgery using autogenous iliac bone and a titanium mesh tray. Functional and morphological results are satisfactory 4 years after surgery.

Thrombopoietin therapy increases platelet yields in healthy platelet donors.

The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 microg/kg or 3 microg/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 x 10(9)/L compared with 366 x 10(9)/L in donors treated with 1 microg/kg PEG-rHuMGDF and 602 x 10(9)/L in donors treated with 3 microg/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 microg/kg and 167% in donors who received 3 microg/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 x 10(11) (range 1.3 x 10(11)-7.9 x 10(11)) platelets compared with 5.6 x 10(11) (range 2.6 x 10(11)-12.5 x 10(11)) or 11.0 x 10(11) (range 7.1 x 10(11)-18.3 x 10(11)) in donors treated with 1 microg/kg or 3 microg/kg PEG-rHuMGDF, respectively. Substandard collections (<3 x 10(11) platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 microg/kg, and 3 microg/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors.

Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin.

Many patients receiving dose-intensive chemotherapy acquire thrombocytopenia and need platelet transfusions. A study was conducted to determine whether platelets harvested from healthy donors treated with thrombopoietin could provide larger increases in platelet counts and thereby delay time to next platelet transfusion compared to routinely available platelets given to thrombocytopenic patients. Community platelet donors received either 1 or 3 microg/kg pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo and then donated platelets 10 to 15 days later. One hundred sixty-six of these platelet concentrates were then transfused to 120 patients with platelets counts 25 x 10(9)/L or lower. Pretransfusion platelet counts (11 x 10(9)/L) were similar for recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Early after transfusion, the median platelet count increment was higher in patients receiving PEG-rHuMGDF-derived platelets: 19 (range, -12-66) x 10(9)/L, 41 (range, 5-133) x 10(9)/L, and 82 (range, -4-188) x 10(9)/L for placebo-, 1-microg/kg-, and 3-micro/kg-derived platelets, respectively. This difference was maintained 18 to 24 hours after transfusion. Transfusion-free intervals were 1.72, 2.64, and 3.80 days for the recipients of the placebo-, 1-microg/kg-, and 3-micro/kg-derived platelets, respectively. The rate of transfusion-related adverse events was not different in recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Therefore, when transfused into patients with thrombocytopenia, platelets collected from healthy donors undergoing thrombopoietin therapy were safe and resulted in significantly greater platelet count increments and longer transfusion-free intervals than platelets obtained from donors treated with placebo.

Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy.

Mucositis, the inflammation and necrosis of mucosal membranes, is a serious and debilitating consequence of many cancer therapies. We were interested in the potential role of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor, r-metHuG-CSF) in the reduction of mucositis. Patients with newly diagnosed small-cell lung cancer (SCLC) were treated with CAE chemotherapy (cyclophosphamide, doxorubicin, and etoposide) and placebo or filgrastim. If patients had an episode of febrile neutropenia, they received unblinded filgrastim in subsequent CAE cycles. Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral candidiasis. Oral mucositis was analyzed using the unadjusted chi-square test, and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model. During cycle 1, placebo-treated patients had more episodes of mucositis (47%) compared with those patients randomized to filgrastim (28%). Across all cycles of treatment, 70% of placebo-treated patients experienced mucositis, compared with 53% of patients randomized to filgrastim. A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim.

Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer.

BACKGROUND: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy. METHODS: We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given. RESULTS: In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base-line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis. CONCLUSIONS: MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer.

BACKGROUND: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte colony formation and platelet production. It is likely to be useful in the management of severe thrombocytopenia. To determine its clinical activity and safety, we gave it to patients with advanced cancer before chemotherapy. METHODS: Patients were randomly assigned to receive either PEG-rHuMGDF or placebo in a three to one ratio. PEG-rHuMGDF was given at a dose of 0.03, 0.1, 0.3, or 1.0 microgram/kg body weight. The study drug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached. FINDINGS: 17 patients, median age 59 years, received either PEG-rHuMGDF (13 patients) or placebo (four patients). PEG-rHuMGDF produced a dose-dependent increase in platelet counts. Patients given placebo. 0.03, and 0.1 microgram/kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12%, and 39%. Those receiving 0.3 and 1.0 microgram/kg of PEG-rHuMGDF had an increase in blood platelets of between 51% and 584%. Platelets rose from day 6 of PEG-rHuMGDF administration and continued to rise after stopping the drug. The platelet count peaked between days 12 and 18 and remained above 450 x 10(9)/L for up to 21 days. There were no alterations in white-blood-cell count or haematocrit, and low toxicity. Platelets taken from patients during PEG-rHuMGDF administration and at the time of peak platelet count were morphologically and functionally normal. INTERPRETATION: The potency with which PEG-rHuMGDF stimulates platelet production and its low toxicity indicate that this is likely to be a useful agent for the management of thrombocytopenia.

Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial.

OBJECTIVE: To determine if filgrastim (recombinant human methionyl granulocyte colony-stimulating factor) used in addition to standard inpatient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Hematology and oncology wards of four teaching hospitals. PATIENTS: 218 patients with cancer who had fever (temperature > 38.2 degrees C) and neutropenia (neutrophil count < 1.0 x 10(9)/L) after chemotherapy. INTERVENTION: Patients were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy with tobramycin and piperacillin. Patients received treatment and remained in the study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days without fever (temperature < 37.5 degrees C) had elapsed. MEASUREMENTS: Days of neutropenia and fever and days in the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics. RESULTS: Compared with placebo, filgrastim reduced the median number of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0 compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both groups). The frequency of the use of alternative antibiotics was similar in the two groups (46% compared with 41%; P = 0.48). The median number of days patients were hospitalized while on study was the same (8.0 days; P = 0.09); however, filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th quartile) by half (relative risk, 2.1 [95% CI, 1.1 to 4.1]; P = 0.02). In exploratory subset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 x 10(9)/L. CONCLUSIONS: Filgrastim treatment used with antibiotics at the onset of febrile neutropenia in patients with cancer who have received chemotherapy accelerated neutrophil recovery and shortened the duration of febrile neutropenia.

Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features.

BACKGROUND: Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, demographic, and perhaps etiologic features. METHODS: The authors investigated and analyzed all of the cases of pathologically confirmed BAC seen at our institution in the hope of discovering new or confirming known features of this disease. RESULTS: When cases of BAC expressed as a percentage of total lung cancers were analyzed in successive 5-year periods from 1955 to 1990, BAC rose from less than 5% to 24.0% (P < 0.001). Much of the increase in BAC occurred in women, as evidenced by a male-to-female ratio that wavered around unity. The mean age of BAC adenocarcinoma patients was 59.2 +/- 11.5 years, compared to 64.1 +/- 13.5 years for non-BAC adenocarcinoma (P < 0.05). BAC also contrasted with other forms of lung cancer by exhibiting a relatively high incidence of multifocality (25% versus 5%) (P < 0.001). There was an association between histologic subtype of BAC and pattern of pulmonic involvement. The mucinous subtype was more strongly associated with diffuse pulmonic involvement, and the sclerotic subtype was more strongly associated with multifocal involvement (P < 0.001). Furthermore, BAC cases exhibited a 20% incidence of dedifferentiation into patterns of poorly differentiated adenocarcinoma, a feature that was more associated with the mucinous and sclerotic subtypes (P < 0.05). CONCLUSIONS: The emergence of BAC as a prominent type of lung cancer should stimulate new basic laboratory and case-control studies to elucidate further the natural history and etiology of this unique disease.

Variations in the use of medication for the treatment of childhood asthma in the Michigan Medicaid population, 1980 to 1986.

Asthma is a leading cause of morbidity in the United States and is a leading cause of disability in children. Prevalence has been shown to be highest in male children, blacks, and urban residents. Racial and residential differences have been attributed to economics. Medicaid claims data allow for the comparison of asthma morbidity and treatment of patients with different demography but of low socioeconomic status. Michigan Medicaid claims data for recipient children between 5 and 14 years of age were used to ascertain demographic factors associated with asthma treatment from 1980 through 1986. A cross-sectional analysis was used. Black asthmatics were found to receive medical care more frequently, but to obtain asthma drugs less frequently than other groups. The prevalence of different prescription asthma preparations also varied by race and residence. Black, urban residents obtained fixed-combination drugs more frequently and steroids less frequently than other groups. Rural patients, in general, had fewer medical contacts but obtained more prescription products per provider contact, whether black or white. Possible reasons for this variation are discussed.

Trends in the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population, 1980 to 1986.

BACKGROUND: Despite advances in therapy, morbidity and mortality rates as a result of pediatric asthma appear to have increased during the past decade. Epidemiologic evidence suggests that these increases disproportionately affected black children and the urban poor. METHODS: With use of data from the Medicaid Management Information System, we estimated the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population for the period 1980 to 1986. RESULTS: Large increases were seen between 1980 and 1984, with leveling off or a slight decline thereafter. In 5- to 9-year-old children, the prevalence of asthma hospitalization increased from 2.3 per 1000 persons in 1980 to 4.5 per 1000 in 1984. Ten- to 14-year-old children demonstrated an increase of 2.2 per 1000 in 1980 to 3.2 per 1000 in 1984. Comparable trends occurred in all strata defined by age, race, residency, and gender. However, the largest increases were noted in urban black children, in which the rate more than doubled from 3.2 per 1000 in 1980 to 7.1 per 1000 in 1984. The adjusted relative risk for asthma hospitalization associated with being male was 1.6 (95% CI: 1.5, 1.7), with being black was 2.2 (95% CI: 2.1, 2.4), and with living in an urban county was 1.1 (95% CI: 1.04, 1.4). CONCLUSIONS: Within this relatively homogeneous low socioeconomic population, black race remained a strong predictor for asthma hospitalization, whereas urban residence was only minimally associated with this outcome.

Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy.

The aim of this study was to determine the usefulness of recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) following conventional chemotherapy for small cell lung cancer. 130 previously untreated patients were randomised to receive either r-metHuG-CSF (230 micrograms/m2) or placebo on days 4-17 following CDE (cyclophosphamide, doxorubicin and etoposide) chemotherapy. Over all cycles, 53% of 64 patients on placebo and only 26% of 65 patients on r-metHuG-CSF had at least one experience of neutropenia with fever defined as a neutrophil count less than 1.0 x 10(9)/l and a temperature > or = 38.2 degrees C (P < 0.002). It resulted in a reduction in the requirement for parenteral antibiotics from 58% in placebo patients compared with 37% in the r-metHuG-CSF group (P < 0.02), and a significant reduction in the incidence of infection-related hospitalisation. Chemotherapy doses were reduced by 15% or more at least once in 61% of the placebo group compared with 29% in the r-metHuG-CSF group (P < 0.001). 47% of the patients treated with placebo and 29% of the patients treated with r-metHuG-CSF experienced at least one cycle with a delay of 2 days or more in the administration of chemotherapy (P < 0.04). r-metHuG-CSF was well tolerated. There were no significant differences between the two groups in terms of response or survival.

Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease.

Despite the well-recognized association between oral contraceptives and deep venous thromboembolism, little is known about the risks associated with currently marketed formulations containing less than 50 micrograms of estrogen. To assess the venous thrombogenicity of low-estrogen oral contraceptives (those containing less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations, we conducted a cohort study of oral contraceptive users between the ages of 15 and 44 years in the Michigan Medicaid population. The period of the study was from 1980 through the third quarter of 1986. A total of 2,739,400 oral contraceptive prescriptions received by 234,218 women were analyzed. Using the low-estrogen cohort as the referent group, the age and calendar period adjusted relative risk of venous thromboembolism in users of intermediate-dose formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p = 0.06). These data provide evidence that the dose-response relation between oral contraceptive estrogen and venous thromboembolism extends from 50 to 30 micrograms of estrogen, the dose range of currently marketed formulations.

Trends in the content and use of oral contraceptives in the United States, 1964-88.

Drug marketing and physician survey data were used to examine trends in the use and hormonal content of oral contraceptives in the United States between 1964 and 1988. Retail prescriptions for oral contraceptives peaked at approximately 68 million in 1973 and have remained between 50 million and 60 million since 1981. Despite this relative consistency in the number of prescriptions, physician "mentions" of oral contraceptives have increased by approximately 75 percent. This increase may reflect closer monitoring of women on oral contraceptives. Use of multiphasic formulations has steadily risen, accounting for 37 percent of the oral contraceptive prescriptions in 1988. Mean estrogen and progestin doses in all types of formulations have steadily declined. A change in the type of estrogen and progestin used in preparations has coincided with this decline in dose. The association between age and use of high-dose formulations seen in the past was no longer evident in 1988. The data demonstrate that oral contraceptive formulations in wide use today differ in hormone content from those of the past, when most of the major studies addressing the risks associated with oral contraceptive use were completed. There is therefore a need to determine the risks and long-term effects associated with these newer formulations.

Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism.

To assess possible differences in the incidence of venous thrombosis and pulmonary embolism associated with oral contraceptives of varying hormonal potencies, the authors conducted a retrospective cohort study in the 15-44 year old Michigan Medicaid population. Cohorts were defined by the progestin- and oestrogen-potencies of oral contraceptives in use at the time of follow-up as classified by an oral contraceptive potency scheme. Using the low-oestrogen-/low-progestin-potency formulations for reference (rate ratio = 1), adjusted rate ratios of 0.8 (95% CI: 0.5 to 1.3, P = 0.41) and 0.6 (95% CI 0.4 to 1.2, P = 0.13) were observed for intermediate-progestin-potency and high-progestin-potency formulations, respectively. Adjusted rate ratios of 1.4 (95% CI: 0.8 to 2.3, P = 0.21) and 2.6 (95% CI: 1.2 to 5.5, P = 0.01) were observed for intermediate- and high-oestrogen-potency formulations. These data suggest a dose-response relationship between oral contraceptive oestrogen potency and venous thromboembolism, whereas no such evidence for a dose-response relationship between oral contraceptive progestin potency and venous thrombo-embolism was found.

Prevalence and treatment of asthma in the Michigan Medicaid patient population younger than 45 years, 1980-1986.

The prevalence and outpatient treatment of asthma were studied in the Michigan Medicaid patient population by use of computerized physician, hospital, and pharmacy reimbursement data to mark and track asthma-related medical transactions. Asthma cases were defined as patients with evidence of at least two diagnoses and prescription drug transactions consistent with asthma. More than 52,000 cases were thus identified. The period prevalence of asthma was estimated on a year-by-year basis. The prevalence of asthma in the population increased from 2.0 per 100 Medicaid patients in 1980 to 2.8 per 100 Medicaid patients in 1986. Prevalence decreased with age until the age of 20 years and increased thereafter, and was higher in male children than in female children. In contrast, asthma was more prevalent in female adults than in male adults. Prevalence was higher in black subjects than in other races and higher in urban residents than in rural residents. The total number of reimbursements for antiasthma medications increased from 60,000 per year to 120,000 per year, and the average number of antiasthma prescriptions per Michigan Medicaid asthma case increased at the rate of 6.6% per year during the study interval. Changes in the preferred types of asthma treatment consistent with changes that have occurred in the general population were observed. These data suggest that the relative and absolute occurrence of asthma and asthma treatment in the Michigan Medicaid population is increasing.