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Excess Risk (excess + risk)
Selected AbstractsProbabilistic risk assessment of reproductive effects of polychlorinated biphenyls on bottlenose dolphins (Tursiops truncatus) from the Southeast United States coastENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2002Lori H. Schwacke Abstract High levels of polychlorinated biphenyls (PCBs) have been reported in the tissues of some species of marine mammals. The high concentrations are of concern because a growing body of experimental evidence links PCBs to deleterious effects on reproduction, endocrine homeostasis, and immune system function. Much of the recent research has focused on determining the exposure of marine mammal populations to PCBs, but very little effort has been devoted to the actual risk assessments that are needed to determine the expected impacts of the documented exposures. We describe a novel risk assessment approach that integrates measured tissue concentrations of PCBs with a surrogate dose-response relationship and leads to predictions of health risks for marine mammals as well as to the uncertainties associated with these predictions. Specifically, we use PCB tissue residue data from three populations of bottlenose dolphins (Tursiops truncatus), study the feasibility of published dose-response data from a surrogate species, and combine this information to estimate the risk of detrimental reproductive effects in female dolphins. Our risk analyses for dolphin populations near Beaufort (NC, USA), Sarasota (FL, USA), and Matagorda Bay (TX, USA) indicate a high likelihood that reproductive success, primarily in primiparous females, is being severely impaired by chronic exposure to PCBs. Excess risk of reproductive failure, measured in terms of stillbirth or neonatal mortality, for primiparous females was estimated as 60% (Beaufort), 79% (Sarasota), and 78% (Matagorda Bay). Females of higher parity, which have previously off-loaded a majority of their PCB burden, exhibit a much lower risk. [source] Evidence for a hallucinogen dependence syndrome developing soon after onset of hallucinogen use during adolescenceINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2006A.L. Stone Abstract This study uses latent class methods and multiple regression to shed light on hypothesized hallucinogen dependence syndromes experienced by young people who have recently initiated hallucinogen use. It explores possible variation in risk. The study sample, identified within public-use data files of the 1999 National Household Survey on Drug Abuse (NHSDA), consists of 1186 recent-onset hallucinogen users, defined as having initiated hallucinogen use within 24 months of assessment (median elapsed time since onset of use ,12 to 13 months). The recent-onset users in this sample were age 12 to 21 at the time of assessment and were between the ages of 10 and 21 at the time of their first hallucinogen use. The NHSDA included items to assess seven clinical features often associated with hallucinogen dependence, which were used in latent class modelling. Latent class analysis, in conjunction with prior theory, supports a three-class solution, with 2% of recent-onset users in a class that resembles a hallucinogen dependence syndrome, whereas 88% expressed few or no clinical features of dependence. The remaining 10% may reflect users who are at risk for dependence or in an early stage of dependence. Results from latent class regressions indicate that susceptibility to rapid transition from first hallucinogen use to onset of this hallucinogen dependence syndrome might be influenced by hallucinogenic compounds taken (for example, estimated relative risk, RR = 2.4, 95% CI = 1.6, 7.6 for users of MDMA versus users of LSD). Excess risk of rapid transition did not appear to depend upon age, sex, or race/ethnicity. Copyright © 2006 John Wiley & Sons, Ltd. [source] Incidence of Cancer Among Female Flight Attendants: A Meta-AnalysisJOURNAL OF TRAVEL MEDICINE, Issue 3 2006Osamu Tokumaru MD Background Airline flight personnel work in a unique environment with exposure to known or suspected carcinogens and mutagens including ionizing cosmic radiation. A meta-analysis was conducted to study whether the occupational exposure of female flight attendants (FA) increased their relative risk of cancer incidence. Methods A bibliographical computer search from 1966 to 2005 of cancer incidence cohort studies of female FA was performed. Combined relative risks (RRc) in cancer incidence were calculated by means of meta-analysis. Results RRc and 95% confidence interval (CI) for malignant melanoma and breast cancer in female FA were 2.13 (95% CI: 1.58,2.88) and 1.41 (1.22,1.62) (p < 0.0001). Excess risk was not significant for all-site cancer with RRc of 1.10 (0.99,1.21). Conclusions The meta-analysis confirmed the significantly increased risks for malignant melanoma and breast cancer in female FA. Increased exposure to cosmic radiation during flight has been suggested as a potential occupational risk factor. Ultraviolet radiation exposure on board seems an unlikely occupational risk, but nonoccupational leisure time sun exposure is a possible risk factor. The etiology of the observed increase in incidence of some cancers remains controversial because assessment of possible confounders, especially nonoccupational exposure factors, has thus far been limited. [source] Postprandial hyperglycaemia in type 2 diabetes: pathophysiological aspects, teleological notions and flags for clinical practiceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2004Eleni I. Boutati Abstract Type 2 diabetes subjects carry an excess risk for micro- and macrovascular disease and a higher cardiovascular morbidity and mortality rate. The beneficial impact of tight glycaemic control,evidenced by the integrated marker of fasting glucose and postprandial glucose values, the HbA1c,for the prevention of microvascular complications is definitely confirmed. Over the past few years, several studies have identified postprandial hyperglycaemia as a better predictor of cardiovascular or even of all-cause mortality, as well as an independent risk factor for atherosclerosis. The continuous glucose monitoring could offer a rationale means for the detection of postprandial hyperglycaemia and ultimately for its effective management. Advances in technology keep a promise for a reliable, convenient and closer to the idea of the artificial endocrine pancreas glucose sensor. Subcutaneous glucose levels charted by one of the new sensors were found to be well correlated with venous glucose measurements. Intervention for a healthy lifestyle is frequently hampered by patients' poor compliance. The availability of diverse antidiabetic agents provides options for targeting the glycaemic goal and a choice more fitted to the particularized pathophysiology of each individual subject. Drugs targeting postprandial glycaemia may prove to represent the ,sine qua non' for the ,return' of postprandial glucose values at a ,non-deleterious' threshold, either as monotherapy for the early stages of the disease or as combination therapy later in the progression of diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] Possible age-associated bias in reporting of clinical features of drug dependence: epidemiological evidence on adolescent-onset marijuana useADDICTION, Issue 1 2003Chuan-Yu Chen ABSTRACT Aims, To probe recent evidence on apparent excess occurrence of marijuana dependence when marijuana smoking starts in adolescence. Design and participants, A national sample of recent-onset marijuana users was identified within public data files of the National Household Survey on Drug Abuse (NHSDA), 1995,98 (1866 adolescents and 762 adults). Measurements, Marijuana dependence was assessed via seven standardized questions about its clinical features, such as being unable to cut down. Multivariate response models (GLM/GEE and MIMIC) were used to evaluate adolescent excess risk and possible item biases. Findings, Among people who had just started to use marijuana, clinical features of marijuana dependence occurred twice as often among adolescents compared to adults, even with statistical adjustment for other covariates (P < 0.01 from GLM/GEE). MIMIC analyses suggest that adolescent-onset users have somewhat higher levels of marijuana dependence, and they also provide evidence of age-associated response bias for some but not all clinical features of marijuana dependence. That is, even with level of marijuana dependence held constant, adolescent recent-onset users were more likely than adults to report being unable to cut down (P = 0.01) and tolerance (P = 0.029). Conclusion, Nosologic, methodological and substantive reasons for observed age-related excess in occurrence of marijuana dependence problems among early onset users deserve more attention in future research. [source] Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2002A. Becker Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng mL,1, respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM-1 levels in the upper quartile (,550 ng mL,1) had a relative risk of cardiovascular mortality of 2·05 (95% confidence interval, 1·10,3·81) compared to subjects with sICAM-1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM-1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33·3 vs. 17·8%). Individuals with a plasma concentration of sICAM-1 higher than 550 ng mL,1 had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk. [source] Paraoxonase activity in two healthy populations with differing rates of coronary heart diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2000Mackness Background The rate of coronary heart disease is over three-fold greater in Belfast than in Toulouse and the excess risk cannot be totally explained by ,classical' risk factors such as total cholesterol, LDL-cholesterol, smoking, etc. Design The effect of the human serum paraoxonase (PON1) 192-genetic polymorphism on plasma lipid and lipoprotein concentrations and on PON1 activity and concentration was investigated in 186 randomly selected healthy subjects from Toulouse and 165 from Belfast. Results The frequency of the R allele of PON1, which has been related to the risk of coronary heart disease, was significantly higher in Belfast (0.33) than in Toulouse (0.24; ,2 = 7.229, P = 0.0072). Subjects from Belfast also had significantly higher serum cholesterol, triglycerides, LDL-cholesterol, and apolipoprotein B, and significantly lower HDL-cholesterol and apolipoprotein A1, but these lipoprotein parameters were independent of the PON1 192-polymorphisms. PON1 activity towards paraoxon was significantly higher in the Belfast population than in Toulouse (median values: 179.7 vs. 129.4 nmol min,1 mL,1 serum, respectively; P < 0.05), which is consistent with our finding of a greater prevalence of the R allele. The median serum concentration of PON1 was 56.3 ,g mL,1 in Belfast, which was significantly lower (P < 0.005) than the level of 71 ,g mL,1 in Toulouse. Conclusions Our results thus provide further support for the hypothesis that populations at increased CHD risk have diminished serum PON1 concentration and an increased prevalence of the R allele of PON1. They are also consistent with reports that the ability of PON1 to hydrolyse paraoxon is inversely related to its capacity to hydrolyse lipid-peroxides, and thus to its antiatherogenic action. [source] Oxidative stress as a multiple effector in Fanconi anaemia clinical phenotypeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005Giovanni Pagano Abstract:, Fanconi anaemia (FA) is a genetic disease characterised by bone marrow failure with excess risk of myelogenous leukaemia and solid tumours. A widely accepted notion in FA research invokes a deficiency of response to DNA damage as the fundamental basis of the ,crosslinker sensitivity' observed in this disorder. However, such an isolated defect cannot readily account for the full cellular and clinical phenotype, which includes a number of other abnormalities, such as malformations, endocrinopathies, and typical skin spots. An extensive body of evidence pointing toward an involvement of oxidative stress in the FA phenotype includes the following: (i) In vitro and ex vivo abnormalities in a number of redox status endpoints; (ii) the functions of several FA proteins in protecting cells from oxidative stress; (iii) redox-related toxicity mechanisms of the xenobiotics evoking excess toxicity in FA cells. The clinical features in FA and the in vivo abnormalities of redox parameters are here reconsidered in view of the pleiotropic clinical phenotype and known biochemical and molecular links to an in vivo prooxidant state, which causes oxidative damage to biomolecules, resulting in an excessive number of acquired abnormalities that may overwhelm the cellular repair capacity rather than a primary deficiency in DNA repair. FA may thus represent a unique model disease in testing the integration between the acquisition of macromolecular damage as a result of oxidative stress and the ability of the mammalian cell to respond effectively to such damage. [source] Areca nut use following migration and its consequencesADDICTION BIOLOGY, Issue 1 2002S. Warnakulasuriya The combined use of areca nut and smokeless tobacco (ST) is practiced particularly in the Indo-Chinese continents. While there is considerable global variation in the use of these products, migrant studies relevant to areca nut use is of considerable interest to epidemiologists in suggesting the extent to which these environment exposures are important in the aetiology of different cancers and other health-related consequences. Studies on Indian migrants to the Malay peninsula, South and east Africa and various Asian ethnic groups resident in several parts of the United Kingdom have shown that the consumption of areca nut (often mixed with ST) is highly prevalent in these communities. Available data on the prevalence of areca chewing among these migrant populations are reviewed here. The carriage of these risk factors from South Asia to other countries has resulted in excess risk of oral cancer in these new settlements. There is also a high incidence of cardiovascular disease, hypertension and late onset diabetes among Indians living in the United Kingdom and there is new evidence to suggest that the combined roles of areca and ST may be contributory. Because of their enhanced financial situation, substance abuse may increase in their new country of domicile. The two products are psychologically addictive and a dependency syndrome related to their use among Asian immigrants to the United Kingdom has been described recently. [source] The role of neuropeptides and neuropeptide-degrading enzymes in wound healingEXPERIMENTAL DERMATOLOGY, Issue 9 2004John E. Olerud Thirty to 40% of diabetic patients develop sensory neuropathy. Neuropathy is a major causal factor in diabetic ulcers. Only 31% of neuropathic diabetic ulcers heal in 20 weeks. Patients with neuropathy have a 15.5-fold excess risk of amputation. Diabetic patients with neuropathy particularly lose epidermal and papillary dermal sensory nerves which release neuropeptides such as substance P (SP). Neutral endopeptidase (NEP), the enzyme that degrades SP, is dramatically over expressed in patients with diabetic neuropathy. SP has positive effect on wound healing. Treatment strategies related to the nervous system for prevention and treatment of diabetic ulcers currently being studied include prevention of neuropathy with tight control of blood glucose, application of neuropeptides, nerve growth factors (NGF), and antagonists of NEP. [source] Mortality differences by APOE genotype estimated from demographic synthesisGENETIC EPIDEMIOLOGY, Issue 2 2002Douglas C. EwbankArticle first published online: 10 JAN 200 Abstract The 4 allele of apolipoprotein E (APOE) is associated with increased risk of two major causes of death in low-mortality populations: ischemic heart disease and Alzheimer's disease. It is less common among centenarians than at younger ages. Therefore, it is likely that it is associated with excess risk of death. This article extends demographic models that estimate relative mortality risks from changes in gene frequencies with age. The resulting demographic synthesis combines gene frequencies with data on mortality by genotype from cohort studies. The model was applied to data from Denmark, Finland, France, Italy, Sweden, and the United States. Near age 50, the 3/4 genotype is associated with a risk of death of 1.34 times that of the 3/3 (95% CI 1.18,1.67). The relative risk for 4/4 is the square of the relative risk for 3/4, 1.81. The 2/3 genotype is protective with a relative risk of 0.84 (0.68,0.93) near age 50. These relative risks move toward 1.0 at the oldest ages and APOE genotype is associated with little variation in mortality over age 100. There are no significant differences in the relative risks by sex. There is little evidence of differences within Europe in the effects of APOE. This approach can be generalized to combine data on genetic risk factors for disease from a wide variety of study designs and sample characteristics. Genet. Epidemiol. 22:146,155, 2002. © 2002 Wiley-Liss, Inc. [source] A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer,,HUMAN MUTATION, Issue 1 2008Zhongning Lin Abstract Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion-induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C>G (c.,6530C>G) in the ERCC6 was examined. We show that the c.,6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case,control study with 1,000 cases and 1,000 controls. The case,control analysis revealed a 1.76-fold (P= × 10,9) excess risk of developing lung cancer for the c.,6530CC carriers compared with noncarriers. The c.,6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR)=9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C>G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. Hum Mutat 29(1), 113,122, 2008. Published 2007, Wiley-Liss, Inc. [source] Cancer patterns in nasopharyngeal carcinoma multiplex families in TaiwanINTERNATIONAL JOURNAL OF CANCER, Issue 7 2009Kelly J. Yu Abstract Genetic and environmental factors have been implicated in the etiology of nasopharyngeal carcinoma (NPC), a tumor known to be closely associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC and have suggested the possible aggregation of NPC and other cancers. We evaluated familial aggregation of cancer in 358 high-risk families with two or more NPC cases enrolled in a NPC genetics study in Taiwan. Participants were linked to the Taiwan National Cancer Registry to identify incident cancers diagnosed after study enrollment (started in 1996) and before December 31, 2005, or death. In total, 2,870 individuals from the NPC Multiplex Family Study contributed 15,151 person-years over an average of 5.3 years of follow-up. One hundred ten incident cancers were identified. Multiple-primary standardized incidence ratios (MP-SIRs) were computed to evaluate overall cancer risk associated with infectious agents and with other tumors. The overall MP-SIR was 1.3 (95% CI: 1.1,1.6), which was largely explained by an excess in NPC (MP-SIR = 15; 95% CI: 10,23). Exclusion of incident NPC diagnoses led to an overall MP-SIR of 1.0 (95% CI: 0.83,1.3). Similarly, the observed excess risk of cancers associated with infectious agents (MP-SIR = 2.0; 95% CI: 1.5,2.6) was driven by the excess in NPC; exclusion of NPC cases led to a reduced MP-SIR that did not differ from 1.0. Analysis of the largest NPC multiplex family study to date confirms the presence of coaggregation of NPC within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. © 2008 Wiley-Liss, Inc. [source] New malignancies following childhood cancer in the United States, 1973,2002INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Peter D. Inskip Abstract The objectives of our study were to quantify risks for developing new malignancies among childhood cancer survivors, identify links between particular types of first and subsequent cancer, and evaluate the possible role of treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in the U.S. during 1973,2002 was identified and followed through SEER cancer registries. Observed-to-expected ratios (O/E) were calculated, and Poisson regression was used to compare risks among treatment groups. Childhood cancer survivors were at nearly 6-fold risk of developing a new cancer relative to the general population (O/E = 5.9, 95% CI: 5.4,6.5). Most common were subsequent primary cancers of the female breast, central nervous system, bone, thyroid gland and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia (ANLL). The greatest risks of subsequent cancers occurred among patients diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was higher among persons whose initial treatment for childhood cancer included radiotherapy, whereas the excess of subsequent ANLL was strongly related to chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year of initial cancer diagnosis among survivors of cancers other than HL, most likely due to increasing use of leukemogenic drugs for solid cancers and non-Hodgkin lymphoma. Childhood cancer survivors are at markedly increased risk of developing a variety of new cancers relative to the general population, but the magnitude of excess risk and specific types of second cancer vary widely by type of first cancer. © 2007 Wiley-Liss, Inc. [source] The risk of pancreatic cancer in patients with gastric or duodenal ulcer diseaseINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Juhua Luo Abstract Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N -nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register-based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record-linkages allowed complete follow-up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3,38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10,40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10,110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4,3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer. © 2006 Wiley-Liss, Inc. [source] The Poor Outcome of Ischemic Stroke in Very Old People: A Cohort Study of Its DeterminantsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2010Licia Denti MD OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants. DESIGN: Cohort, observational. SETTING: University hospital. PARTICIPANTS: One thousand five hundred fifty-five patients with first-ever ischemic stroke consecutively referred to an in-hospital Clinical Pathway program were studied. MEASUREMENTS: The relationship between age and 1-month outcome (death, disability (modified Rankin Scale 3,5), and poor outcome (modified Rankin Scale 3,6)) was assessed, with adjustment for several prognostic factors. RESULTS: Six hundred twelve patients aged 80 and older showed worse outcome after 1 month than those who were younger, in terms of mortality (19% vs 5%, hazard ratio (HR)=3.85, 95% confidence interval (CI)=2.8,5.4) and disability (51% vs 33%, odds ratio (OR)=3.16, 95% CI=2.5,4.0), although in multivariate models, the adjusted HR for mortality decreased to 1.47 (95% CI=1.0,2.16) and the ORs for disability and poor outcome decreased to 1.76 (95% CI=1.32,2.3.) and 1.83 (95% CI=137,2.43), respectively. Stroke severity, the occurrence of at least one medical complication, and premorbid disability explained most of the risk excess in the oldest-old. CONCLUSION: Stroke outcome is definitely worse in very old people, and most of the excess risk of death and disability is attributable to the higher occurrences of the most-severe clinical stroke syndromes and of medical complications in the acute phase. These represent potential targets for preventive and therapeutical strategies specifically for elderly people. [source] Association Between Vertebral Fracture and Increased Mortality in Osteoporotic Patients,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003Tarja Jalava Abstract Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk. Introduction: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself. Methods: We studied 677 women and men with osteoporosis, 28,88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score < ,2.5 and ,3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry. Results: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health,including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age,the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI. 0.93, 6.23). Conclusions: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk. [source] Use of Inhaled Corticosteroids and Risk of FracturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001T. P. Van Staa Abstract Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10,1.20), 1.22 (95% CI, 1.04,1.43), and 1.51 (95% CI, 1.22,1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94,1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85,1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71,1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid. [source] A long-term follow-up study on the natural course of oral leukoplakia in a Swedish population-based sampleJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2007A. Roosaar Aim:, To assess the natural course of screening-detected oral leukoplakia (OL) among non-consulting individuals. Methods:, A cohort of 555 individuals with OL, confirmed in 1973,1974 during a population-based survey, were followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 104 drawn from the 297 surviving cohort members who still were living in the area in 1993,1995 was invited to a re-examination. Sixty-seven of them attended. Results:, At the time of re-examination OL had disappeared in 29 (43%) individuals. There was a statistically significant association between cessation of/no smoking habits in 1993,1995 and the disappearance of OL. Never/previous daily smokers were thus over-represented among individuals whose OL had disappeared compared to those with persisting OL [n = 23 (82%) vs. n = 18 (47%), P < 0.01]. Eighteen (78%) of the twenty three non-smokers with disappearing OL had quit after the initial examination. One man and two women developed oral cancer during follow-up while 0.7 and 0.07, respectively, were expected. Conclusion:, Smoking cessation was associated with an increased disappearance of OL. Hence, at least one-fourth had lesions that could be classified as tobacco-related. Small observed and expected numbers prohibited firm conclusions about a possible excess risk of developing oral cancer. [source] Injury Risk Among Medically Identified Alcohol and Drug AbusersALCOHOLISM, Issue 1 2001Ted R. Miller Background: Although nonfatal injury prevalence is higher among substance abusers than in the general population, few studies have estimated the injury risk for clinically recognized substance abusers. The extant studies, moreover, analyze rates of visits for injury treatment rather than rates of injury events. This study estimates the excess risk of medically treated and hospitalized nonoccupational injury for people under age 65 with medically identified substance abuse problems and private health care coverage. Method: We conducted a retrospective cohort study by using medical claims data from Medstat Systems, Inc., with a longitudinal database of health care claims for 1.5 million people with health care coverage from 70 large corporations. Claims histories for anyone who had an alcohol-related or drug-related primary or secondary diagnosis during 1987 to 1989 were analyzed. A random sample was selected from the remaining people without a substance abuse diagnosis in their medical records. Injury rates were compared among groups. We used logistic regression to estimate odds of medically treated and hospitalized injury, controlling for demographics. Results: Medically identified substance abusers had an elevated risk of injury in a 3-year period; alcohol and drug abusers had the highest risk (58%), followed by drug-only abusers (49%), alcohol-only abusers (46%), and controls (38%). Alcohol and drug abusers were almost four times as likely to be hospitalized for an injury in a 3-year period when compared with controls. Injury risks were elevated substantially more for female then male substance abusers. Conclusions: This study greatly improves on available information about the risk of injury for drug and multiple-substance abusers. Medically identified substance abusers, especially adult women, have a higher probability of injury, more hospitalized injuries, and more injury episodes per person injured than nonabusers. More aggressive identification and subsequent treatment of female substance abusers appear warranted. [source] Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23 796 consecutive autopsiesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2006Å. ELIASSON Summary.,Background:,The relationship between atherothrombotic disease and venous thromboembolism (VTE) remains unclear. Patients and methods:,In a cohort of 23 796 consecutive autopsies, performed using a standardized procedure and representing 84% of all in-hospital deaths between 1970 and 1982 in an urban Swedish population, we investigated the relationship between verified arterial thrombosis and VTE, with the hypothesis that patients with thrombosis in major artery segments have increased odds of VTE. Results:,We found an increased risk of VTE in patients with arterial thrombosis (Odds ratio; OR adjusted for gender and age 1.4, 95% confidence interval; CI 1.3,1.5) (P < 0.001). Patients with cervico-cranial and peripheral artery thrombosis had an excess risk even when controlling for age and major concomitant diseases. A negative association between coronary thrombosis and VTE in the univariate analysis (OR 0.7; 95% CI 0.6,0.8) (P < 0.001), was less pronounced in the multivariate analysis (OR 0.8; 95% CI 0.7,1.0) (P = 0.016). Conclusions:,A positive association between atherothrombosis and VTE was confirmed, except in patients with coronary thrombosis, where IHD as competing death cause is a possible confounder. Our findings indicate a potential for directed prevention, but may also imply similarities in etiology. [source] Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000,2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2008Alexander M. Walker MD, DrPH Abstract Background The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices. Objectives To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas. Methods We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head-to-head comparisons using propensity-score-stratified Cox proportional hazards models, examining risks both on-treatment and during total follow-up before regimen switches. Results For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94,1.14) for total follow-up and 1.05 (0.92,1.19) for on-treatment time. For MI, the hazard ratios were 1.07 (0.89,1.27) for total follow-up and 1.21 (0.95,1.54) for on-treatment time. Conclusions The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on-treatment time will require combination with the results of other studies to provide a reliable assessment. Copyright © 2008 John Wiley & Sons, Ltd. [source] Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2007Frank de Vries Pharm D Abstract Introduction Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. Objectives To examine the association between use of beta-2 agonists and risk of hip/femur fracture. Methods We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history. Results A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41,3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41,2.66) for daily dosages of ,1600,µg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02,2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80,2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. Conclusion We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists. Copyright © 2006 John Wiley & Sons, Ltd. [source] Use of postmenopausal hormone therapy since the Women's Health Initiative findings,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 12 2005Judith Parsells Kelly MS Abstract Purpose To assess how use of postmenopausal hormone therapy (PHT) has changed since the Women's Health Initiative (WHI) trial was halted early due to an excess risk of stroke and other adverse outcomes. To estimate whether use of alternative drugs to treat menopausal symptoms (e.g., selective serotonin reuptake inhibitors [SSRIs], soy) has increased. Methods Women were interviewed in the Slone Survey, a random-digit-dial (RDD) survey of current medication use in a representative national sample. Information was obtained on PHT including dose, route, and reason for use, and on use of alternative drugs to treat menopausal symptoms. There were 3853 women aged ,50 years, interviewed from 1/2001 to 6/2004. Results The average weekly prevalence of PHT declined 57%, from 28% in the first half of 2002 to 12% in the first half of 2004. Use declined for conjugated estrogens (CE) and for other estrogens, taken either alone or with progestin. The decrease exceeded 50% in most strata of age, race, education, and region. The proportion of PHT users taking 0.3 mg CE did not change. Comparing prevalence in 2004 with prevalence in 2002, there was no material increase in use of black cohosh (2.0% in 2004) or soy (2.0%) and use of SSRIs was somewhat lower (8.9%). Conclusions These population-based usage data demonstrate a large decline in PHT use among women of postmenopausal age. The proportion of CE users taking lower doses has not increased. On a population basis, millions fewer women are using PHT in 2004 than before the WHI results were published, but there has been no appreciable increase in use of alternative therapies for menopausal symptoms over the same period. Copyright © 2005 John Wiley & Sons, Ltd. [source] Biases affecting the proportional reporting ratio (PRR) in spontaneous reports pharmacovigilance databases: the example of sertindolePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2003Nicholas Moore Abstract Background Automated measures of reporting disproportionality in databases of spontaneous reports of adverse drug reactions are an emerging tool to identify drug-related alerts. Sertindole, a new atypical neuroleptic known to prolong the QT interval, was suspended in November 1998 because the proportion of reports of fatal reactions suggesting arrhythmia among all reports with sertindole was almost ten times higher than that for other atypical neuroleptics in the UK. This excess risk was not predicted in preclinical data and had not been found in premarketing trials. Method Reporting patterns over time were analysed. Prescription Event Monitoring (PEM) studies and a large retrospective cohort allowed for the comparison of actual death rates with atypical neuroleptics, and to assess which proportion of the deaths that occurred were reported. Results There were indications of possible skewing of reporting related to notoriety, surveillance and market size effects. Death rates in PEM studies were essentially similar between sertindole and other neuroleptics. Cardiac deaths had been two to three times more often reported than other causes of death. Conclusion Proportional reporting ratios indicate differential reporting of possible reactions, not necessarily differential occurrence. There was no indication of an actual increase of risk of all causes or cardiac deaths during sertindole treatment, but only an increased risk of its being reported. The suspension of sertindole was rescinded by Committee on Proprietary Medicinal Products (CPMP) in October 2001. Copyright © 2003 John Wiley & Sons, Ltd. [source] Case,control study of male germ cell tumors nested in a cohort of car-manufacturing workers: Findings from the occupational historyAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 10 2010Ingo Langner PhD Abstract Background To examine whether the previously observed excess risk of male germ cell cancer in a cohort of car-manufacturing workers can be attributed to occupational activities inside and/or outside the car industry. Methods A nested case,control study among workers in six plants included 205 cases of germ cell cancer and 1,105 controls, individually matched by year of birth (±2 years). Job periods of the individual occupational histories were coded based on the International Standard Classification of Occupations (ISCO) and the industrial classification of economic activities (NACE). Odds ratios (ORs) and corresponding 95%-confidence intervals (CI) for ever-never and cumulative employment were calculated by conditional multivariate logistic regression adjusted for cryptorchidism. Results Significantly increased risks were observed for machinery fitters and assemblers (A) (OR,=,1.8, 95% CI 1.25,2.53) and "workers not elsewhere classified" (OR,=,2.10, 95% CI 1.27,3.54), but no trend was observed for employment duration in either occupational group. Stratification of job group A by metal-cutting and non-cutting jobs yielded ORs of 1.87 (95% CI 1.31,2.67) and of 1.24 (95% CI 0.68,2.28), respectively. Among "plumbers, welders, sheet & structural metal workers" (adjusted OR 1.4, 95% CI 0.99,1.95) only "structural metal preparers and erectors" showed a substantially increased risk (OR,=,2.30; 95% CI 1.27,4.27). Conclusions Our results do not fully explain the increased incidence of germ cell cancer in the cohort, but support previous findings showing increased risks among metal workers. These risks were most strongly pronounced in metal-cutting activities. Am. J. Ind. Med. 53:1006,1018, 2010. © 2010 Wiley-Liss, Inc. [source] Mortality of older construction and craft workers employed at department of energy (DOE) nuclear sitesAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 9 2009John M. Dement PhD Abstract Background The U.S. Department of Energy (DOE) established medical screening programs at the Hanford Nuclear Reservation, Oak Ridge Reservation, the Savannah River Site, and the Amchitka site starting in 1996. Workers participating in these programs have been followed to determine their vital status and mortality experience through December 31, 2004. Methods A cohort of 8,976 former construction workers from Hanford, Savannah River, Oak Ridge, and Amchitka was followed using the National Death Index through December 31, 2004, to ascertain vital status and causes of death. Cause-specific standardized mortality ratios (SMRs) were calculated based on US death rates. Results Six hundred and seventy-four deaths occurred in this cohort and overall mortality was slightly less than expected (SMR,=,0.93, 95% CI,=,0.86,1.01), indicating a "healthy worker effect." However, significantly excess mortality was observed for all cancers (SMR,=,1.28, 95% CI,=,1.13,1.45), lung cancer (SMR,=,1.54, 95% CI,=,1.24,1.87), mesothelioma (SMR,=,5.93, 95% CI,=,2.56,11.68), and asbestosis (SMR,=,33.89, 95% CI,=,18.03,57.95). Non-Hodgkin's lymphoma was in excess at Oak Ridge and multiple myeloma was in excess at Hanford. Chronic obstructive pulmonary disease (COPD) was significantly elevated among workers at the Savannah River Site (SMR,=,1.92, 95% CI,=,1.02,3.29). Conclusions DOE construction workers at these four sites were found to have significantly excess risk for combined cancer sites included in the Department of Labor' Energy Employees Occupational Illness Compensation Program (EEOCIPA). Asbestos-related cancers were significantly elevated. Am. J. Ind. Med. 52:671,682, 2009. © 2009 Wiley-Liss, Inc. [source] Identification of occupational cancer risk in British Columbia: A population-based case,control study of 2,998 lung cancers by histopathological subtypeAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2009Amy C. MacArthur MHSc Abstract Background Few studies have investigated occupational lung cancer risk in relation to specific histopathological subtypes. Methods A case,control study was conducted to evaluate the relationship between lung cancer and occupation/industry of employment by histopathological subtype. A total of 2,998 male cases and 10,223 cancer controls, diagnosed between 1983 and 1990, were identified through the British Columbia Cancer Registry. Matched on age and year of diagnosis, conditional logistic regression analyses were performed for two different estimates of exposure with adjustment for potentially important confounding variables, including tobacco smoking, alcohol consumption, marital status, educational attainment, and questionnaire respondent. Results For all lung cancers, an excess risk was observed for workers in the primary metal (OR,=,1.31, 95% CI, 1.01,1.71), mining (OR,=,1.53, 95% CI, 1.20,1.96), machining (OR,=,1.33, 95% CI, 1.09,1.63), transport (OR,=,1.50, 95% CI, 1.08,2.07), utility (OR,=,1.60, 95% CI, 1.22,2.09), and protective services (OR,=,1.27, 95% CI, 1.05,1.55) industries. Associations with histopathological subtypes included an increased risk of squamous cell carcinoma in construction trades (OR,=,1.25, 95% CI, 1.06,1.48), adenocarcinoma for professional workers in medicine and health (OR,=,1.73, 95% CI, 1.18,2.53), small cell carcinoma in railway (OR,=,1.62, 95% CI, 1.06,2.49), and truck transport industries (OR,=,1.51, 95% CI, 1.00,2.28), and large cell carcinoma for employment in the primary metal industry (OR,=,2.35, 95% CI, 1.11,4.96). Conclusions Our results point to excess lung cancer risk for occupations involving exposure to metals, polyaromatic hydrocarbons and asbestos, as well as several new histopathologic-specific associations that merit further investigation. Am. J. Ind. Med. 52:221,232, 2009. © 2008 Wiley-Liss, Inc. [source] One agent, many diseases: Exposure-response data and comparative risks of different outcomes following silica exposure,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2005Kyle Steenland Abstract Background Evidence in recent years indicates that silica causes lung cancer, and probably renal disease, in addition to its well-known relationship to silicosis. There is also suggestive evidence that silica can cause arthritis and other auto-immune diseases. Silica has, therefore, joined a handful of other toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple serious diseases. Methods The available exposure-response data for silica and silicosis, lung cancer, and renal disease are reviewed. We compare the corresponding excess risks (or absolute risks in the case of silicosis) of death or disease incidence by age 75 for these three diseases, subsequent to a lifetime (45 years) of exposure to silica at current US standard (0.1 mg/m3 respirable crystalline silica). Results The absolute risk of silicosis, as defined by small opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges from 47% to 77% in three cohort studies with adequate follow-up after employment. The absolute risk of death from silicosis is estimated at 1.9% (0.8%,2.9%), based on a pooled analysis of six cohort studies. The excess risk of lung cancer death, assuming US male background rates, is 1.7% (0.2%,3.6%), based on a pooled analysis of ten cohort studies. The excess risk of end-stage renal disease (assuming male background rates) is 5.1% (2.2%,7.3%), based on a single cohort. The excess risk of death from renal disease is estimated to be 1.8% (0.8%,9.7%), based on a pooled analysis of three cohorts. Conclusions Keeping in mind that the usual OSHA acceptable excess risk of serious disease or death for workers is 0.1%, it is clear that the current standard is far from sufficiently protective of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a higher risk than either mortality from silicosis or lung cancer, although the data are based on fewer studies. Am. J. Ind. Med. 48:16,23, 2005. © 2005 Wiley-Liss, Inc. [source] Quantitative exposure-response for silica dust and lung cancer in Vermont granite workers,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2004Michael D. Attfield BSc Abstract Background Excess lung cancer mortality among the exposed Vermont granite workers has been reported. These studies were based on job and tenure surrogates, with the potential for misclassification and inability to evaluate quantitative exposure-response. Methods Industrial hygiene data collected from 1924 to 1977 was analyzed in conjunction with mortality data to examine quantitative exposure-response for silica, lung cancer, and other lung diseases. A person-years analysis was undertaken by cumulative exposure group, including lagged and unlagged tabulations. Poisson models were fitted to untransformed and log transformed exposure. Results The results indicated a clear relationship of lung cancer, tuberculosis, pneumoconiosis, non-malignant lung disease, and kidney cancer with cumulative exposure. An exposure to 0.05 mg/m3 from age 20 to 64 was associated with a lifetime excess risk of lung cancer for white males of 27/1,000. Conclusions The results of this study of workers exposed almost exclusively to silica and no other major occupational confounding exposures indicate a clear exposure-response for lung cancer. Am. J. Ind. Med. 45:129,138, 2004. Published 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||