Leon F. Burmeister

Low dose long-term corticosteroid therapy in rheumatoid arthritis: An analysis of serious adverse events

PURPOSE The purpose of this study was to better define the toxicity of low dose (less than or equal to 15 mg/d prednisone or equivalent) long-term (greater than 1 year) corticosteroids in the treatment of rheumatoid arthritis (RA). PATIENTS AND METHODS We examined an historical cohort of 112 RA patients on low dose (6.1 +/- 3.1 mg/d, mean +/- SD) long-term (6.2 +/- 4.6 years) prednisone (CS) and compared them to 112 matched RA patients not using prednisone (CO). CS were matched one-to-one with CO for sex (75% women), age (+/- 5 yrs), race (98% white), and duration of disease (+/- 5 yrs). Subjects were determined by review of unselected medical records from three distinct rheumatology practice settings. For CS, charts were abstracted from the date of prednisone start for predefined adverse events (AEs). RESULTS Ninety-two (92) AEs were noted in CS versus 31 in CO and included: fracture (CS:21 versus CO:8), serious infections (CS:14 versus CO:4), gastrointestinal (GI) bleed or ulcer (CS:11 versus CO:4), and cataracts (CS:17 versus CO:5). At time of first AE, CS prednisone average dose was 7.0 +/- 2.6 mg with a duration of 4.9 +/- 3.9 years. Stepwise multiple logistic regression analysis was used to create a model which included all clinically relevant variables and all parameters significantly different at the cohort inception. Prednisone average dose of greater than 10 to less than or equal to 15 mg/d correlated most strongly with the development of an AE (Odds Ratio (OR) = 32.3, 95% Confidence Interval (CI) 4.6, 220). Average prednisone 5 to 10 mg (OR = 4.5, 95% CI 2.1, 9.6), RA nodules (OR = 3.9, 95% CI 1.9, 8.0), and bony erosions (OR = 2.4, 95% CI 1.2, 4.7) also entered the final model. Kaplan Meier survival curves for the development of the first AE showed a dose-response relationship between prednisone and AE occurrence, independent of rheumatoid nodules. Subset analyses utilized a nested case control design for the development of three serious AEs: fractures, serious infections, and GI events. These analyses revealed possible relationships between prednisone use and the development of each specific AE (prednisone use OR: fracture 3.9, 95% CI 0.8, 18.1; infection 8.0, 95% CI 1.0, 64.0; and GI event 3.3, 95% CI 0.9, 12.1). CONCLUSIONS Although disease severity is an important confounding factor, low dose long-term prednisone use equal to or greater than 5 mg/d is correlated with the development of specific adverse events in a dose-dependent fashion.

Racial Differences in Factors that Influence the Willingness to Participate in Medical Research Studies

PURPOSE The relative absence of racial/ethnic minorities among medical research subjects is receiving considerable attention because of recent government mandates for their inclusion in all human subject research. We examined racial differences in the prevalence of sociocultural barriers as a possible explanation for the underrepresentation of African Americans in medical research studies. METHODS During 1998-1999, a total of 198 residents of the Detroit Primary Metropolitan Statistical Area (PMSA) participated in a survey that examined impediments to participation in medical research studies. Chi square tests and logistic regression analyses were used to examine the association between race, issues related to trust of medical researchers, and the willingness to participate in medical research studies. RESULTS Study results indicate that African Americans and whites differ in their willingness to participate in medical research. Racial differences in the willingness to participate in a medical research are primarily due to the lower level of trust of medical research among African Americans. African American respondents were also somewhat less willing to participate if they attribute high importance to the race of the doctor when seeking routine medical care, believed that minorities bear most of the risks of medical research, and if their knowledge of the Tuskegee Study resulted in less trust in medical researchers. CONCLUSION These data reiterate the need for medical researchers to build trusting relationships with minority communities. Researchers can begin by acknowledging the previous medical abuse of minority research participants, discussing their specific plans to assure the protection of study participants, and explaining the need for the participation of racial/ethnic minorities including studies that specifically target or that are likely to result in disproportionate representation of racial/ethnic minorities among study participants.

Why are African Americans under‐represented in medical research studies? Impediments to participation

OBJECTIVES In accordance with the NIH Revitalization Act of 1993, the National Institutes of Health and the Alcohol, Drug and Mental Health Administration require grant applicants and cooperative agreement participants to include minorities in human subject research. In an environment characterized by diminishing research dollars, this mandate has increased the pressure on investigators to determine factors that impede minority participation and to develop strategies to overcome these impediments. METHODS An extensive review of the literature was conducted to identify the factors possibly responsible for the low participation levels of African Americans in medical research studies and to highlight areas for further research. The items examined included the historical relationship between African Americans and medical researchers and the attitudes, perceptions and beliefs of potential participants and researchers as they relate to the low representation of African Americans in medical research. RESULTS The factors identified as possible impediments to African American participation included distrust of the medical/scientific community, poor access to primary medical care, the failure of researchers to recruit African Americans actively, the alienation of minority health professionals, lack of knowledge about clinical trials, language and cultural barriers. CONCLUSIONS Well-designed, relevant, ethical research in conjunction with an appreciation of the many barriers to participation are paramount to increasing African American presence in clinical research.

Changing patterns of red blood cell transfusion in very low birth weight infants

OBJECTIVE Anemia develops in increasing numbers of critically ill very low birth weight (VLBW) infants who survive the neonatal period, and they receive multiple red blood cell (RBC) transfusions. Despite their need for prolonged medical treatment, we hypothesized that VLBW infants presently receive fewer RBC transfusions as a result of the growing awareness of transfusion risks and improvement of neonatal care. METHODS RBC transfusion practices and clinical outcomes in infants with birth weights of 1.5 kg or less were analyzed retrospectively in three selected years: 1982, before awareness of the human immunodeficiency virus; 1989, before surfactant availability; and 1993, before erythropoietin approval. RESULTS Progressive declines in RBC transfusions, donor exposures, and transfusion volumes occurred concurrently with decreases in morbidity and mortality rates. Transfusions per infant (mean +/- SD) declined from 7.0 +/- 7.4 in 1982 to 5.0 +/- 5.8 in 1989 to 2.3 +/- 2.7 in 1993 (p < 0.001). This decline was associated with a decrease in pretransfusion hematocrit (33.6% +/- 2.8% in 1982, 34.2% +/- 3.7% in 1989, and 29.8% +/- 5.1% in 1993; p < 0.001). The distribution of RBC transfusions given by week of life among study years did not change; 70% of RBC transfusions were given within the first 4 weeks, when infants are sickest. Although the percentage of VLBW infants weighing more than 1 kg at birth and never receiving any RBC transfusions increased with time (17% in 1982, 33% in 1989, and 64% in 1993), more than 95% of infants weighing 1 kg or less in all years received transfusions. CONCLUSIONS Overall administration of neonatal transfusions has decreased markedly, most likely because of multiple factors. Because most RBC transfusions are given to infants weighing 1 kg or less in the first weeks of life, therapeutic strategies should focus on this group of VLBW infants during this critical period. The temporal changes observed in transfusion patterns emphasize the importance of including concurrent controls in future studies evaluating transfusion interventions.

Factors that influence African-Americans' willingness to participate in medical research studies.

The underrepresentation of African‐Americans among medical research participants is receiving considerable attention because of recent government mandates for the inclusion of all racial/ethnic groups in human subject research. Therefore, there is a need to determine factors that influence minority enrollment in medical research studies.

Asthma and Farm Exposures in a Cohort of Rural Iowa Children

Epidemiologic studies of farm children are of international interest because farm children are less often atopic, have less allergic disease, and often have less asthma than do nonfarm children—findings consistent with the hygiene hypothesis. We studied a cohort of rural Iowa children to determine the association between farm and other environmental risk factors with four asthma outcomes: doctor-diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze, and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least one of these four health outcomes was found in more than a third of the cohort. Multivariable models of the four health outcomes found independent associations between male sex (three asthma outcomes), age (three asthma outcomes), a personal history of allergies (four asthma outcomes), family history of allergic disease (two asthma outcomes), premature birth (one asthma outcome), early respiratory infection (three asthma outcomes), high-risk birth (two asthma outcomes), and farm exposure to raising swine and adding antibiotics to feed (two asthma outcomes). The high prevalence of rural childhood asthma and asthma symptoms underscores the need for asthma screening programs and improved asthma diagnosis and treatment. The high prevalence of asthma health outcomes among farm children living on farms that raise swine (44.1%, p = 0.01) and raise swine and add antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal histories of allergy, suggests the need for awareness and prevention measures and more population-based studies to further assess environmental and genetic determinants of asthma among farm children.

Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma.

To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkins lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkins disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.

AS‐1 red cells for neonatal transfusions: a randomized trial assessing donor exposure and safety

Background: Despite recent optimism about the use of erythropoietin therapy to treat the anemia of prematurity, very‐low‐birth‐weight infants who are severely ill receive multiple red cell (RBC) transfusions. Many physicians transfuse relatively fresh RBCs to newborn infants, exposing them to multiple donors and possibly increasing their risk of acquiring transfusion‐transmitted infections.

Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's lymphoma among male farmers (United States)

AbstractObjective: Data from three population-based case–control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkins lymphoma (NHL) among white male farmers. Methods: The data set included 748 cases of non-Hodgkins lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression. Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures. Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States).

Objectives: To update the cancer mortality patterns among Iowa (United States) farmers for the years 1987-93 and compare these results with those previously reported for 1971-86 as well as relate the PMR patterns to risk-factor survey data.Methods: We extracted usual occupation and cause of death from 88,090 Iowa death certificates for White males aged 20 and older for the years 1987-93. Proportional mortality ratios (PMR), adjusted for age, and 95 percent confidence intervals (CI) were calculated using deaths among nonfarmers to generate expected numbers. We compared lifestyle profiles for farmers and nonfarmers using male controls (n = 1,596) from a population-based case-control study conducted in Iowa from 1986-89.Results: Iowa farmers had deficit PMRs for all-cause cancer mortality (PMR = 0.92, CI = 0.90-0.94) and for lung (PMR = 0.70, CI = 0.66-0.73), liver (PMR = 0.65, CI = 0.50-0.86), and other cancer sites strongly related to smoking and alcohol use. Farmers at all ages had excess deaths for cancers of the prostate (PMR = 1.26, CI = 1.19-1.33), rectum (PMR = 1.29, CI = 1.07-1.56), brain (PMR = 1.10, CI = 0.92-1.32), multiple myeloma (PMR = 1.17, CI = 0.98-1.40), non-Hodgkins lymphoma (PMR = 1.09, CI = 0.96-1.23), and Hodgkins disease (PMR = 1.62, CI = 1.04-2.54). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (PMR = 1.52, CI = 1.26-1.85) and skin melanoma (PMR = 1.60, CI = 1.07-2.38), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (PMR = 1.18, CI = 1.04-1.34), lip (PMR = 1.58, CI = 0.59-4.21), and leukemia (PMR = 1.26, CI = 1.09-1.46). Since the 1970s, the PMR for stomach cancer has declined to expected values, while the PMRs for prostate, large intestine, pancreas, and Hodgkins disease have increased; PMRs for other sites are consistent with earlier data. A survey from 1986-89 showed that farmers, compared with nonfarmers, smoked less, used less alcohol, had less formal education, and consumed more total calories, and calories from protein, fat, and meat while consuming fewer calories from fruits and vegetables.Conclusions: Iowa farmers continue to be at elevated risk of mortality due to certain cancers, and, of particular interest, the risk for prostate and colon cancer appears to be increasing since 1970. Cancer Causes and Control 1998, 9, 311-319