Estimating the completeness of physician billing claims for diabetes case ascertainment using population-based prescription drug data.

INTRODUCTION: Changes in physician reimbursement policies may hinder the collection of billing claims in administrative data; this can result in biased estimates of disease prevalence and incidence. However, the magnitude of data loss is largely unknown. The purpose of this study was to estimate completeness of capture of disease cases for Manitoba physicians paid by fee-for-service (FFS) and non-fee-for-service (NFFS) methods. METHODS: Manitoba's administrative data were used to identify a cohort (≥ 20 years) with a new diabetes medication between 1 April, 2007, and 31 March, 2009. Cohort members were classified by payment method of the prescribing physician (i.e. FFS vs. NFFS). The cohort was then classified as missing or not missing a diabetes diagnosis using physician claims and hospital records. Then, χ2 statistics were used to test for differences in the characteristics of the two groups. RESULTS: The cohort consisted of 12 394 individuals; 86.4% had a prescription for a diabetes medication from an FFS physician. A total of 1172 physicians (81.8% FFS) prescribed these medications for the cohort. Cohort members with a prescription from an FFS physician were older and more likely to reside in the urban Winnipeg health region than those with a prescription from a NFFS physician. A greater percentage of NFFS physicians' cases were missing a diabetes diagnosis (18.7%vs. 14.9% for FFS physicians). CONCLUSION: The results suggest minimal loss of physician claims associated with remuneration policies in Manitoba. This method of assessing data completeness could be applied to other chronic diseases and jurisdictions to estimate completeness.

TITRE: Estimation de l'exhaustivité des données de facturation des médecins pour la détermination des cas de diabète au moyen des données sur les médicaments d'ordonnance. INTRODUCTION: Les changements dans les politiques de remboursement des me´decins peuvent faire obstacle a` la collecte des donne´es administratives de facturation des me´decins, ce qui pourrait mener a` des estimations biaise´es de la pre´valence et de l'incidence des maladies. L'ampleur de cette perte potentielle de donne´es demeure cependant largement inconnue. Notre e´tude vise a` estimer l'exhaustivite´ de la couverture des cas de maladie pour le Manitoba par les me´decins re´mune´re´s a` l'acte (RA) et par les me´decins non re´mune´re´s a` l'acte (NRA). MÉTHODOLOGIE: Les donne´es administratives du Manitoba ont servi a` cre´er une cohorte dont les membres (20 ans et plus) devaient avoir pris un nouveau me´dicament pour le diabe`te entre le 1er avril 2007 et le 31 mars 2009. Ces membres ont e´te´ classe´s par mode de paiement du me´decin prescripteur (c'est-a`-dire re´mune´re´s a` l'acte ou non re´mune´re´s a` l'acte), puis selon s'ils avaient ou non rec¸u de diagnostic de diabe`te d'apre`s les donne´es de facturation des me´decins et des dossiers d'hoˆpitaux. On a utilise´ des analyses statistiques w2 pour tester les diffe´rences de caracte´ristiques entre les deux groupes. RÉSULTATS: La cohorte se composait de 12 394 individus, dont 86,4 % avaient rec¸u une ordonnance de me´dicament pour le diabe`te d'un me´decin RA. Au total, 1 172 me´decins (81,8 % RA) ont prescrit ce type de me´dicaments pour la cohorte. Les membres de la cohorte ayant rec¸u une ordonnance d'un me´decin RA e´taient plus aˆge´s et plus susceptibles de re´sider dans la re´gion sanitaire deWinnipeg que ceux qui avaient rec¸u une ordonnance d'un me´decin NRA. Un plus grand pourcentage de cas traite´s par des me´decins NRA n'avait pas rec¸u de diagnostic de diabe`te (18,7 %, contre 14,9 % pour les me´decins RA). CONCLUSION : Les re´sultats sugge`rent une perte minimale de donne´es de facturation des me´decins associe´e aux politiques de re´mune´ration au Manitoba. Cette me´thode d'e´valuation de l'exhaustivite´ des donne´es pourrait eˆtre applique´e a` d'autres maladies chroniques et a` d'autres secteurs de compe´tence.

Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia.

PURPOSE: We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors. METHODS: Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40-69 years; cervical: 21-75 years). Kaplan-Meier and Cox proportional hazards models were used to assess time to first screen. RESULTS: Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16). CONCLUSIONS: Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening.

Application of a national administrative case definition for the identification of pre-existing diabetes mellitus in pregnancy.

INTRODUCTION: Accurate ascertainment of pregnant women with pre-existing diabetes allows for the comprehensive surveillance of maternal and neonatal outcomes associated with this chronic disease. METHOD: To determine the accuracy of case definitions for pre-existing diabetes mellitus when applied to a pregnant population, a cohort of women who were pregnant in Nova Scotia, Canada, between 1991 and 2003 was obtained from a population-based provincial perinatal database, the Nova Scotia Atlee Perinatal Database (NSAPD). Person-level data from administrative databases using hospital discharge abstract data and outpatient physician services data were linked to this cohort. Various algorithms for defining diabetes mellitus from the administrative data, including the algorithm suggested by the National Diabetes Surveillance System (NDSS), were compared to a reference standard definition from the NSAPD. RESULTS: Validation of the NDSS case definition applied to this pregnant population demonstrated a sensitivity of 87% and a positive predictive value (PPV) of 66.4%. Use of ICD-9 and ICD-10 diagnostic codes among hospitalizations with diabetes mellitus in pregnancy showed important increases in sensitivity and PPV, especially for those pregnancies delivered in tertiary centres. In this population, pregnancy-related administrative data from the hospitalization database alone appear to be a more accurate data source for identifying pre-existing diabetes than applying the NDSS case definition, particularly when pregnant women are delivered in a tertiary hospital. CONCLUSION: Although the NDSS definition of diabetes performs reasonably well compared to a reference standard definition of diabetes, using this definition for evaluating maternal and perinatal outcomes associated with diabetes in pregnancy will result in a certain degree of misclassification and, therefore, biased estimates of outcomes.

Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial.

OBJECTIVE: Eosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitor-refractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated. METHODS: Eleven adults with active EoO (>20 peak eosinophil number/high power field (hpf) and dysphagia) were randomised to 750 mg of mepolizumab (n = 5) or placebo (n = 6) and received two intravenous infusions, 1 week apart. Those not in complete remission (<5 peak eosinophil number/hpf) after 8 weeks received two further doses 4 weeks apart, 1500 mg of mepolizumab or placebo. The effect of mepolizumab was assessed clinically, endoscopically, histologically, and via blood and tissue biomarkers. RESULTS: As assessed by immunofluorescence, a marked reduction of mean oesophageal eosinophilia (p = 0.03) was seen in the mepolizumab group (-54%) compared with the placebo group (-5%) 4 weeks after initiation of treatment. No further reduction of eosinophil numbers was observed in response to the two additional infusions in either group. Mepolizumab reduced tenascin C (p = 0.033) and transforming growth factor beta1 (p = 0.05) expression in the oesophageal epithelial layer 13 weeks after initiation of treatment. Clinically, limited improvement of symptoms was seen, although a trend was seen between 4 and 13 weeks after initiation of mepolizumab treatment. Mepolizumab was well tolerated. CONCLUSIONS: Mepolizumab significantly reduced eosinophil numbers in oesophageal tissues in adult patients with active EoO, and changes in the expression of molecules associated with oesophageal remodelling were reversed. Minimal clinical improvement was achieved in a subgroup of patients with EoO. Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose level. TRIAL REGISTRATION NUMBER: NCT00274703.

Diabetes mellitus following gestational diabetes: role of subsequent pregnancy.

OBJECTIVE: This study was designed to determine the rate of diabetes up to 13 years after pregnancies complicated by gestational diabetes and to identify risk factors for developing diabetes. The role of a subsequent pregnancy, with and without gestational diabetes, was also examined. DESIGN: This was a retrospective cohort study of women with gestational diabetes. POPULATION AND SETTING: Women who had gestational diabetes in their first pregnancy between 1989 and 2002 were identified through a population-based perinatal database in Nova Scotia, Canada. METHODS: Subsequent diagnoses of diabetes, up to 13 years after the first pregnancy, were obtained from physician billing and hospital discharge databases. Cox proportional hazards regression models were used to estimate adjusted relative risks (RR) and 95% confidence intervals. MAIN OUTCOME MEASURES: Diagnosis of diabetes after pregnancy. RESULTS: Of the 1401 nulliparous women with gestational diabetes, 251 women (17.9%) developed diabetes in the follow-up period. The cumulative incidence at 1, 5, and 10 years was 5.9, 14.8, and 22.2%, respectively. Factors significantly associated with an increased risk of developing diabetes mellitus included a pre-pregnancy weight of > or = 86 kg (RR = 1.8, 95% CI 1.2-2.9), insulin therapy during the index pregnancy (RR = 4.1, 95% CI 2.1-7.9), neonatal hypoglycaemia (RR = 2.6, 95% CI 1.6-4.2), and a subsequent pregnancy with gestational diabetes (RR = 2.3, 95% CI 1.6-3.4). CONCLUSION: Indicators of the severity of gestational diabetes, defined by insulin use, neonatal hypoglycaemia, and recurrent gestational diabetes in a subsequent pregnancy, are important in predicting a subsequent diagnosis of diabetes. Our findings do not support the theory that subsequent pregnancy, per se, increases the risk of developing diabetes.

Variation in pharmacy prescription refill adherence measures by type of oral antihyperglycaemic drug therapy in seniors in Nova Scotia, Canada.

OBJECTIVE: To examine the association between pharmacy prescription refill adherence by type of oral antihyperglycaemic medications used in seniors in Nova Scotia, Canada. RESEARCH DESIGN AND METHODS: Pharmacy and health care utilization data from April 1993 to March 1996 for Nova Scotia Seniors' Pharmacare beneficiaries treated with 1st and 2nd generation sulphonylureas and biguanides was analysed. Refill adherence was quantified by two proportions: number of days beneficiaries had a medication surplus compared with the total period of observation and gaps in treatment compared with the total period of observation. Analysis examined association of type of oral antihyperglycaemic agent and dosing on refill adherence, after adjustment for age, gender and hospital use. RESULTS: A total of 3358 beneficiaries met the study criteria. The mean refill adherence rate [continuous multiple-interval measure of medication availability (CMA)] was 86 +/- 0.4% SE and continuous measure of medication gaps (CMG) was 16 +/- 0.4% SE. Use of biguanides was associated with lower odds of having a medication surplus. The use of 2nd generation sulphonylureas and biguanides, and use of agents with a dosage frequency of more than one dose per day was associated with medication gaps. CONCLUSIONS: Many beneficiaries taking antihyperglycaemic agents adhered well to prescribed therapy. The proportion of days not covered by medications averaged 16%. Beneficiaries taking medications once a day were more likely to have good refill adherence. Further work is needed to compare prescription refill adherence rates with other adherence measures and clinical outcomes. These methods are useful for establishing baseline adherence, monitoring the success of programmes designed to improve adherence, and determining cost-effectiveness of drug regimens.

Proximate and contextual socioeconomic determinants of mortality: multilevel approaches in a setting with universal health care coverage.

Investigations of contextual factors (income inequality, cultural disruption, access to health and social services, safety and crime rate, and others) have received little emphasis by epidemiologists, although a few have demonstrated the importance of such factors for mortality, particularly in the United States. To expand current understanding of the importance of contextual factors, the authors evaluated mortality in a longitudinal study in Nova Scotia, Canada, where all residents have greater access to health and social services and where income inequalities are smaller than in the United States. A total of 2,116 participants were followed from 1990 through December 1999, linked to the 1991 Canada Census as a source of neighborhood characteristics, and analyzed using individual-level and multilevel logistic regression. Well-educated and high-earning persons fared better. Neighborhood socioeconomic characteristics (neighborhood income, educational level, unemployment rate), in contrast, were not significantly associated with mortality. However, within advantaged neighborhoods, the importance of individual income and education for mortality was increased relative to disadvantaged neighborhoods. The latter findings may direct health policy aimed at reducing health inequalities.

Physician characteristics in relation to cardiovascular drugs commonly prescribed for hypertension in Nova Scotia.

BACKGROUND: Cardiovascular drugs are the most frequently prescribed class of drugs in Canada. Among them, drugs used to treat hypertension are the single largest component. Variability in how these drugs are prescribed should be based on the specific characteristics of patients. However, some evidence shows that physician characteristics can also play a substantial role in prescribing trends. Such variation is also associated with varying beneficial and adverse patient outcomes. PURPOSE: To determine whether prescribing patterns of drugs used to treat hypertension in elderly patients in Nova Scotia varied by physician characteristics. METHODS: A retrospective, population-based descriptive study was done using the Nova Scotia Pharmacare program data for the fiscal year 1995/96. The unit of analysis was the individual physician. All drugs indicated in the management of hypertension were included for the analysis. RESULTS: Of 1466 physicians included in the analysis, 1004 were family physicians (FPs) and/or general practitioners (GPs), 155 were internal medicine specialists and 307 were other specialists. Fifty-eight per cent of 103,193 eligible senior citizens received at least one of the study medications. FPs and/or GPs prescribed 95.9% of all the study drugs. Internists prescribed proportionately fewer angiotensin-converting enzyme inhibitors, thiazides and other diuretics compared with the FPs and/or GPs but more beta-blockers and calcium channel blockers. A large proportion of the FPs and/or GPs (55.3%) prescribed less than 10% of the total day's supply of drugs, whereas a small proportion of FPs and/or GPs (16.3%) prescribed 52.6% of all the study drugs. There was no variation in the distribution of the types of antihypertensives prescribed based on physician age, sex or volume of prescribing. A slight variation in prescribing was seen with location of practice. CONCLUSIONS: Patterns of prescribing cardiovascular drugs used to treat hypertension were remarkably unaffected by physician characteristics. This finding counters other evidence in the literature that has raised concerns over prescribing patterns of certain types of physicians. Prescribing patterns may vary for other drug classes, but for this group of antihypertensives, little variability was found.

Eosinophil infiltration and degranulation in normal human tissues: evidence for eosinophil degranulation in normal gastrointestinal tract.

Eosinophils play an important role in the pathogenesis of inflammatory diseases such as bronchial asthma and host immunity to parasitic infections. Deposition of eosinophil granule proteins and concomitant tissue damage have been documented in various diseases. Here, we review and summarize results of our immunofluorescence studies of eosinophil infiltration and degranulation in various normal human tissues. Furthermore, because eosinophil infiltration and degranulation are not normally present in healthy tissues, we examine whether eosinophil infiltration and degranulation normally occur in the small intestine and whether tissue procurement methods affect the extent of eosinophil infiltration and degranulation there. Hematopoietic and lymphatic tissues, including the thymus, showed eosinophil infiltration, but the only organ showing remarkable eosinophil infiltration and degranulation was the gastrointestinal (GI) tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel. These results suggest that tissue procurement methods affect the degree of eosinophil degranulation in the GI tract and that, among normal human body organs, both eosinophil infiltration and degranulation only occur in the GI tract.

Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis.

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP). METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale. RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group. CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.

Estimation of hospital costs for colorectal cancer care in Nova Scotia.

BACKGROUND: Colorectal cancer (CRC) is the second most common invasive cancer in Canada. Estimates of the costs of care allow estimation of the cost effectiveness of screening for premalignant and early disease. OBJECTIVE: To estimate, from administrative data, the hospital costs incurred by a population-based cohort of CRC cases over three years from diagnosis. DESIGN: All Nova Scotia residents with CRC who were diagnosed in 1990 were identified from the Nova Scotia Cancer Registry. These cases were linked to the administrative files of the Nova Scotia Department of Health, which contain information on diagnosis, procedures and length of stay for all admissions and day surgery visits to Nova Scotia hospitals. MEASUREMENTS: The lengths of stay and hospital-specific per diem rates were used as the measures of resource use. The costs were analyzed in terms of the extent of spread at diagnosis; the time period after diagnosis; the time period before death; and, for typical cases, the age and presence of comorbidity identified during the initial surgical admission. RESULTS: The estimated three-year hospital cost for the complete cohort of 593 cases was $9.8 million. This cost was significantly less for cases with local spread, highest in the six months around, and after diagnosis and in the final six months of life, and highest in the typical cases (patients who were older and had significant comorbid conditions). CONCLUSIONS: Hospital-specific per diem rates and lengths of stay are an approximate measure of hospital resource use.

Linkage of the Canadian Study of Health and Aging to provincial administrative health care databases in Nova Scotia.

The Canadian Study of Health and Aging (CSHA) was a cohort study that included 528 Nova Scotian community-dwelling participants. Linkage of CSHA and provincial Medical Services Insurance (MSI) data enabled examination of health care utilization in this subsample. This article discusses methodological and ethical issues of database linkage and explores variation in the use of health services by demographic variables and health status. Utilization over 24 months following baseline was extracted from MSI's physician claims, hospital discharge abstracts, and Pharmacare claims databases. Twenty-nine subjects refused consent for access to their MSI file; health card numbers for three others could not be retrieved. A significant difference in healthcare use by age and self-rated health was revealed. Linkage of population-based data with provincial administrative health care databases has the potential to guide health care planning and resource allocation. This process must include steps to ensure protection of confidentiality. Standard practices for linkage consent and routine follow-up should be adopted. The Canadian Study of Health and Aging (CSHA) began in 1991-92 to explore dementia, frailty, and adverse health outcomes (Canadian Study of Health and Aging Working Group, 1994). The original CSHA proposal included linkage to provincial administrative health care databases by the individual CSHA study centers to enhance information on health care utilization and outcomes of study participants. In Nova Scotia, the Medical Services Insurance (MSI) administration, which drew the sampling frame for the original CSHA, did not retain the list of corresponding health card numbers. Furthermore, consent for this access was not asked of participants at the time of the first interview. The objectives of this study reported here were to examine the feasibility and ethical considerations of linking data from the CSHA to MSI utilization data, and to explore variation in health services use by demographic and health status characteristics in the Nova Scotia community cohort.

Management of high blood cholesterol levels in Nova Scotian adults: comparison with the NCEP II and European clinical practice guidelines.

OBJECTIVE: To compare the prevalence of dietary and drug treatment for high blood cholesterol levels with indication for treatment according to the National Cholesterol Education Program (NCEP) II and European clinical practice guidelines. STUDY DESIGN: A population-based, cross-sectional study. PATIENTS AND METHODS: Data were from the 1995 Nova Scotia Health Survey. Patients were 2078 respondents aged 20 to 74 years who provided blood samples. Based on cardiovascular risk factors, respondents were compared with guidelines to determine eligibility for dietary and antilipemic drug therapy. RESULTS: According to the NCEP II and European guidelines, 21% and 13%, respectively, of the population were estimated to be dietary therapy candidates and 12% and 4%, respectively, were estimated to be candidates for antilipemic drug therapy. Less than half of the dietary therapy candidates, according to either guideline, reported being diagnosed, and only about half of those diagnosed reported having received dietary therapy. Overall, 6% to 15% of the NCEP II drug therapy candidates and 12% to 37% of the European drug therapy candidates were estimated to be receiving antilipemic drugs. Only about 45% of the NCEP II and 60% of the European drug therapy candidates reported being diagnosed as having high blood cholesterol levels, and only about 50% of the NCEP II- and 60% of the European-diagnosed drug therapy candidates reported having received dietary therapy. The estimated prevalence of antilipemic drug therapy among diagnosed drug therapy candidates was 12% to 29% for the NCEP II and 12% to 52% for the European guidelines. CONCLUSIONS: Dietary therapy and antilipemic drug therapy were underused relative to the NCEP II and European guidelines as a result of underdiagnosis and low use of treatment after diagnosis. Large differences in the recommendations of the 2 guidelines, however, show lack of consensus as to who should be treated and point to the need for additional research on this issue.

Trends in the prevalence and treatment of hypertension in Halifax County from 1985 to 1995.

BACKGROUND: The objective of this study was to document changes in the prevalence and treatment of hypertension in Halifax County from 1985 to 1995 in an effort to observe, at the population level, the consequences of the availability of new antihypertensive medications. METHODS: The study population comprised a random sample of Halifax County residents, aged 25-64 years, who responded to the 1985 and 1995 surveys of the Halifax County MONICA Project and residents who responded to the Nova Scotia Health Survey conducted in 1995. Data from the two 1995 surveys were pooled. Information on hypertension awareness and use of medication were obtained through questionnaires, and blood pressure was measured according to a standard protocol, using phase I and V of Korotkoff sounds as respective markers for systolic and diastolic pressures. Uncontrolled hypertension was defined as a systolic pressure of 140 mm Hg or greater and a diastolic pressure of 90 mm Hg or greater. Changes in the prevalence of hypertension, prescribing trends and medication costs were examined, and the association between the type of antihypertensive treatment and characteristics of the respondents with self-reported hypertension was investigated by multivariate logistic regression. RESULTS: Of the 917 people interviewed in 1985 and the 1338 in 1995, 274 (29.9%) and 356 (26.6%), respectively, reported a history of hypertension. When age was controlled for, the proportion of respondents reporting hypertension did not differ between survey years or between men and women. The proportion of treated respondents who had uncontrolled hypertension increased between 1985 and 1995, from 32.6% to 57.4% among men and from 38.0% to 42.6% among women. An increase was seen in the use of calcium-channel blockers (from 2.1% to 19.7%) and angiotensin-converting-enzyme inhibitors (from 5.2% to 25.4%); the proportion of patients receiving combination therapy or diuretics decreased (from 39.6% to 15.6% and from 31.3% to 17.2% respectively). These changes were associated with an increase in the average daily cost of medication from $0.48 to $0.85 per patient. INTERPRETATION: The shift to new antihypertensive drugs was not associated with improved blood pressure control, but it was associated with an increase in average medication costs per patient. Uncontrolled hypertension remains a public health problem.

Reactivity of monoclonal antibodies EG1 and EG2 with eosinophils and their granule proteins.

Use of the murine monoclonal antibodies EG1 and EG2 has been based on the assumption that EG2 recognizes activated eosinophils. We examined the reactivity of EG1 and EG2 with eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and stimulated and nonstimulated eosinophils from normal donors. By radioimmunoassay, EG1 recognized only ECP, whereas EG2 recognized both ECP and EDN. By Western blot, EG1 reacted with ECP, EG2 reacted with both ECP and EDN, but EG2 could not distinguish between lysates of stimulated and nonstimulated eosinophils. By immunofluorescence, EG1 and EG2 at 20 microg/mL stained 95-100% of nonstimulated eosinophils, regardless of fixative; EG1 and EG2 at 0.1 microg/mL stained 61-90% of acetone- and paraformaldehyde-fixed and only 5-21% of methanol-fixed nonstimulated eosinophils. Thus, the reactivity of EG1 and EG2 with eosinophils depends on the method of fixation and antibody concentration; and EG2, in contrast to previous reports, cannot reliably discriminate between resting and activated eosinophils.

Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis.

Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), especially in its early stages. Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients with PBC. It remains unknown, however, whether eosinophils in PBC patients are functionally activated and whether UDCA inhibits eosinophil activation. In the present study, we systematically examined eosinophil dynamics in the blood and liver in patients with stage I to II PBC before and after UDCA treatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radioimmunoassay and quantitated eosinophil degranulation using computer-assisted morphometry after MBP immunohistochemistry. Before UDCA treatment, patients with PBC (n = 25) showed significantly higher circulating eosinophil counts (P <. 05) and serum concentrations of MBP (P <.0005) and EDN (P <.02) compared with patients with chronic viral hepatitis (n = 22), autoimmune hepatitis (n = 10), and obstructive jaundice (n = 12). Four-week UDCA treatment significantly reduced blood eosinophil counts (P <.0001) and serum MBP (P <.0001) and EDN (P <.0001) levels in PBC patients. MBP immunohistochemistry and computer-assisted quantitative morphometry showed infiltration and degranulation of eosinophils in the portal tract in patients with PBC and significant reductions in the number of sites and the area occupied by extracellular MBP deposits after UDCA treatment for 2 years (P <.02) but not in placebo-treated patients. Our results suggest that eosinophils in patients with PBC are not only increased in number, but also release granule proteins, and that UDCA treatment inhibits this eosinophil activation/degranulation.

Underuse of acetylsalicylic acid in individuals with myocardial infarction, ischemic heart disease or stroke: data from the 1995 population-based Nova Scotia Health Survey.

OBJECTIVE: To determine current patterns of acetylsalicylic acid (ASA) use in Nova Scotia for individuals with self-reported myocardial infarction, stroke or ischemic heart disease. DESIGN: Descriptive, cross-sectional, population-based study using data from the 1995 Nova Scotia Health Survey (NSHS). The NSHS was based on a probability sample and was representative of the Nova Scotia adult population by age, sex and region. Survey data were obtained by standardized home interviews conducted by trained public health nurses. SETTING: The province of Nova Scotia in 1995. PARTICIPANTS: Survey respondents who reported having a myocardial infarction, stroke or ischemic heart disease were assessed. RESULTS: Among those who reported a history of myocardial infarction, stroke or ischemic heart disease, 55% (95% CI 47% to 63%), 49% (95% CI 38% to 61%) and 54% (95% CI 39% to 68%), respectively, reported using ASA at the time of the survey. Overall, only 53% of those with cardiovascular disease were using ASA. Exclusion of persons with potential contraindications to ASA did not significantly increase these proportions. CONCLUSIONS: ASA appears to be underused in those at high risk for future vascular events. Further research is required to investigate determinants of ASA use and to increase appropriate use of ASA.

Eosinophil infiltration and degranulation in normal human tissue.

Localization of eosinophil granule major basic protein by immunofluorescence permits recognition of both eosinophil infiltration and degranulation. Over the past decade and a half, our laboratory has shown that eosinophil infiltration and degranulation occur in many diseased tissues in humans; among normal tissues studied as controls, only the gut showed striking eosinophil infiltration and degranulation. Using an indirect immunofluorescence procedure for the detection of major basic protein, we extended our analyses of normal human tissues to include tissues from essentially all body organs; a total of 117 biopsy/autopsy specimens were analyzed. To determine whether the method of tissue procurement affected the level of eosinophil degranulation in the normal gastrointestinal tract, normal proximal jejunum from six patients was biopsied using either an endoscopic forceps or a scalpel at the time of elective surgery and examined by immunofluorescence. Spleen, lymph node, and thymus tissues showed eosinophil infiltration with scant evidence of degranulation, but the only organ showing both eosinophil infiltration and remarkable degranulation was the gastrointestinal tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel (P = 0.021). These results indicate that tissue procurement methods affect the degree of eosinophil degranulation in the gut. Thus, among normal human body organs, both eosinophil infiltration and appreciable degranulation consistently occur only in the gut.