Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Estimating the cost of expanding an apheresis program

To determine the cost of expanding blood product operations, the concept of marginal cost must be used. This article reports the development and implementation of a method of costing increases in collecting plasma using apheresis operations. The model takes into account the fact that certain resource inputs--notably, direct labor and machines--increase in discrete steps rather than in a continuous manner. To address this fact, a stepwise cost analysis function was developed, which related operating costs to the volume of apheresis collections. This function was used to predict the marginal costs of potential increases in the supply of plasma at a blood center in Canada. Differences were noted in the cost of plasma in Canada and the United States, much of which could be attributed to different standards regarding the volume of plasma per collection and to differences in pricing materials.     

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Associations of the beta-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis

INTRODUCTION: The factor XIII Val34Leu (100 G-->T) and beta-fibrinogen Hae III (-455 G-->A) gene variants have been associated with reduced risk of venous thrombosis, but not in all studies. METHODS: We investigated the associations of these polymorphisms with risk of venous thrombosis in a prospective, population-based study of 21,680 men and women aged 45-100 years at enrollment. Factor XIII 100 G/T and beta-fibrinogen -455 G/A were analyzed on stored DNA from 511 thrombosis cases and 1028 control subjects without thrombosis during follow up. RESULTS: The beta-fibrinogen A allele was present in 24.4% of cases and 32.3% of controls. Compared to GG subjects, the age, race, and sex adjusted odds ratio (OR) of venous thrombosis was 0.77 (95% CI 0.59-0.99) for GA subjects, and 0.60 (95% CI 0.31-1.16) for AA subjects. The adjusted OR of thrombosis associated with factor XIII 100 G/T was 1.01 (95% CI 0.81-1.26) for GT subjects and 0.45 (95% CI 0.44-1.19) for TT subjects, compared to GG. For both genotypes, ORs of thrombosis were similar in whites and non-whites, although there were no non-white fibrinogen AA cases. beta-fibrinogen -455 GA or AA attenuated the thrombosis risk associated with obesity (from 2.14 to 1.25) and factor V Leiden (from 3.89 to 2.36). CONCLUSIONS: beta-fibrinogen -455 G/A, but not factor XIII 100 G/T, was associated with a lower risk of venous thrombosis in this general population sample. beta-fibrinogen -455 A may attenuate the increased thrombosis risk associated with obesity or factor V Leiden.     

Clinical significance of a high ankle-brachial index: insights from the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND: The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown. METHODS: Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high ABI groups (ABI>1.3, >1.4, and >1.5) and compared the risk factor profile and CVD event rates of the normal ABI group to each high ABI group. RESULTS: The prevalence of high ABI was 5.5% for ABI>1.3, 1.2% for ABI>1.4, and 0.37% for ABI>1.5. Compared with participants with a normal ABI, those with ABI>1.3 had a lower prevalence of hypertension and current smoking. The ABI>1.3 group had a greater mean body mass index, but was characterized by fewer pack years of smoking and lower systolic and diastolic blood pressures than the normal ABI group. The prevalence of diabetes, left ventricular hypertrophy, claudication, and coronary heart disease and mean values of fibrinogen, factor VIII activity, von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial thickness were similar between the two ABI groups. The risk factor profiles of the ABI>1.4 and >1.5 groups were also not statistically significantly different from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the normal ABI group, 7.6 in the ABI>1.3 group, 7.6 in the ABI>1.4 group, and 7.4 in the ABI>1.5 group. The CVD event rates of the high ABI groups were similar to that of the normal ABI group. CONCLUSION: Individuals with a high ABI are not characterized by a more adverse atherosclerosis risk factor profile and do not suffer greater CVD event rates than those with a normal ABI.     

Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999-2004

OBJECTIVE: This study examined trends and costs of second-generation antipsychotic polypharmacy among Medicaid beneficiaries with schizophrenia in San Diego County. METHODS: Medicaid data were used to identify 15,962 persons with schizophrenia receiving antipsychotic medications between 1999 and 2004. The yearly proportion of beneficiaries receiving second-generation antipsychotic polypharmacy, duration of polypharmacy, inpatient admissions, and pharmaceutical costs were examined. RESULTS: The proportion of clients receiving second-generation antipsychotic polypharmacy increased from 3.3% in 1999 to 13.7% in 2004, whereas annual antipsychotic medication costs increased from $4,128 to $5,231 (2004 dollars). Among those receiving second-generation polypharmacy, the percentage receiving second-generation polypharmacy for 12 months increased from 5.1% to 14.4%, and the percentage hospitalized increased from 7.2% to 9.0%. CONCLUSIONS: The prevalence of long-term second-generation antipsychotic polypharmacy and its associated costs increased substantially between 1999 and 2004. Prescribing antipsychotic polypharmacy is an unproven and costly strategy that if left unchanged could lead to administrative efforts to cut costs and dictate practice.     

Risk factors for meningioma in postmenopausal women: results from the Iowa Women's Health Study

Few risk factors for meningioma, aside from increasing age and female sex, have been identified. We investigated risk factors for meningioma in elderly women, a group with a high incidence. We evaluated associations of demographic, lifestyle, medical history, and anthropometric variables with risk of meningioma in the Iowa Women's Health Study (IWHS), a population-based, prospective cohort study. Risk factors were collected via questionnaires mailed in 1986 and 1992. Incident meningiomas were identified via linkages to Medicare. Cox regression models were used to examine the association of risk factors with meningioma incidence. The mean age at baseline of the 27,791 women in the analysis cohort was 69.3 years (range, 65.0-84.6 years). During 291,021 person-years of follow-up, 125 incident meningiomas were identified. After adjusting for age, lower levels of physical activity (relative risk [RR] , 0.68 for high versus low; P for trend = .039), greater body mass index (BMI; RR, 2.14 for ≥35 versus 19.5-24.9 kg/m(2); P for trend = .0019), greater height (RR, 2.04 for >66 versus ≤62 inches; P for trend = .013), and a history of uterine fibroids (RR, 1.72; 95% confidence interval, 1.19, 2.50) were positively associated with meningioma risk in multivariate analysis. BMI at age 18 and 30 years were not associated with risk. There were no associations with menstrual or reproductive factors or other medical history and lifestyle factors. Physical activity, BMI, height, and history of uterine fibroids were associated with meningioma risk in older women. The positive association with height suggests a role for early life influences on risk, whereas the associations with BMI and physical activity suggest a role for modifiable factors later in life.