Search

Background: Fractures are a manifestation of osteoporosis, but therapeutic interventions to reduce the risk of recurrent fractures are not widespread. Objective: To identify predictors of osteoporosis treatment in postmenopausal women following distal forearm fracture. Methods: This population-based retrospective cohort study included all postmenopausal women, 45 years or older, residing in Olmsted County, Minnesota, who sustained a distal forearm fracture due to minimal trauma (a fall from standing height or under) in 1993 to 1997. Complete medical records were reviewed for each subject and Cox proportional hazards regression was used to evaluate the relationship of baseline demographic and clinical characteristics to therapeutic interventions for osteoporosis within 12 months following the fracture. Results: A total of 343 women with a mean age of 70.5 years had a minimal trauma distal forearm fracture. Within 12 months, 83% had seen a nonorthopedic physician. Of these, 17% had a pharmacologic osteoporosis intervention and the 12-month actuarially estimated cumulative incidence of any intervention was 18% (95% confidence interval [CI], 14%-22%). In a multivariate analysis, treatment was more likely to be offered to those with a prior diagnosis of osteoporosis (relative risk [RR], 2.08; 95% CI, 1.21-3.58), previous distal forearm fracture (RR, 2.38; 95% CI, 1.30-4.34), or history of cigarette smoking (RR, 1.86; 95% CI, 1.11-3.12). Conclusions: Effective osteoporosis interventions are underutilized among postmenopausal women who experience an osteoporotic fracture. Further work is needed to overcome barriers to optimal osteoporosis management in these women who are at high risk for future complications of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: The introduction of routine measurement of serum calcium levels led to a sharp increase in the incidence of primary hyperparathyroidism in the early 1970s.Objective: To evaluate the trends in the incidence of primary hyperparathyroidism since the mid-1970s.Setting: Rochester and Olmsted County, Minnesota.Design: Population-based descriptive study.Patients: All residents of Rochester, Minnesota, who received an initial diagnosis of primary hyperparathyroidism between 1965 and 1992 were identified through the medical records linkage system of the Rochester Epidemiology Project. Included as persons having definite cases (92% of the total) were patients with pathologically confirmed hyperparathyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia that had lasted for more than a year and had no cause other than primary hyperparathyroidism.Measurements: Incidence rates were calculated and directly standardized to the population structure of white persons in the United States in 1990.Results: From 1965 to June 1974 (the prescreening era), the age- and sex-adjusted incidence of primary hyperparathyroidism in Rochester was 15 cases per 100,000 person-years. After measurement of calcium levels was added to the automated serum chemistry panel in July 1974, the incidence increased to 112 per 100,000 person-years in 1975 and then decreased somewhat, reflecting a sweeping effect. Despite improved case ascertainment, however, the incidence rate has continued to decrease; in 1992, the incidence was 4 per 100,000 person-years. A few patients had complications that might have been caused by hyperparathyroidism (22% between 1965 and June 1974 and 6% thereafter), and survival was not impaired in either period. The maximum serum calcium levels did not change (P = 0.15).Conclusions: The progressive decrease in the incidence of primary hyperparathyroidism is unexpected and suggests a significant change in the epidemiology of this disease. [ABSTRACT FROM AUTHOR]

Primary Objective: Automated external defibrillators (AEDs) are used with increasing frequency in the United States by first responders (FR) such as police officers (PO) or firefighters (FF). However, FR satisfaction with use of AEDs has not been investigated. We hypothesized that FR satisfaction is comparable with that of paramedics (PA) and that, among those who have defibrillated with AEDs, those who have restored a pulse before PA arrival have a higher level of satisfaction than those who have not restored a pulse.Materials and Methods: A 21-item questionnaire with closed answers was sent to FR and PA in four communities. Each answer was scored 0, 1 or 2. A score between 10 and 16 correlated with the highest satisfaction level.Results: 276 out of 311 questionnaires were returned (89%). Two hundred and eleven respondents (35 PA, 70 FF and 106 PO) had used an AED and 99 FF and PO had restored a pulse before PA arrival. The satisfaction level of PO, FF and PA was high as demonstrated by the scores: 13.26, 13.07 and 13.39, respectively. Use of AED and pulse restoration resulted in higher scores than those of groups who had been trained only and who had not restored a pulse.Conclusion: FR demonstrated a high level of satisfaction with using AEDs, and also had a favorable attitude toward implementation of AED use. Restoration of a pulse was clearly a factor responsible for a higher satisfaction. This positive attitude should encourage further implementation of early defibrillation programs in non-medical first responder settings. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cirrhosis is a chronic granulomatous cholangitis, characteristically associated with antimitochondrial antibodies. Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown. Methods: To identify genetic loci conferring a risk for primary biliary cirrhosis, we carried out a genomewide association analysis in which DNA samples from 2072 Canadian and U.S. subjects (536 patients with primary biliary cirrhosis and 1536 controls) were genotyped for more than 300,000 single-nucleotide polymorphisms (SNPs). Sixteen of the SNPs most strongly associated with primary biliary cirrhosis were genotyped in two independent replication sets. We carried out fine-mapping studies across three loci associated with primary biliary cirrhosis. Results: We found significant associations between primary biliary cirrhosis and 13 loci across the HLA class II region; the HLA-DQB1 locus (encoding the major histocompatibility complex class II, DQ β chain 1) had the strongest association (P=1.78×10−19; odds ratio for patients vs. controls, 1.75). Primary biliary cirrhosis was also significantly and reproducibly associated with two SNPs at the IL12A locus (encoding interleukin-12α), rs6441286 (P=2.42×10−14; odds ratio, 1.54) and rs574808 (P=1.88×10−13; odds ratio, 1.54), and one SNP at the IL12RB2 locus (encoding interleukin-12 receptor β2), rs3790567 (P=2.76×10−11; odds ratio, 1.51). Fine-mapping analysis showed that a five-allele haplotype in the 3′ flank of IL12A was significantly associated with primary biliary cirrhosis (P=1.15×10−34). We found a modest genomewide association (P<5.0×10−5) with the risk of disease for SNPs at the STAT4 locus (encoding signal transducer and activator of transcription 4) and the CTLA4 locus (encoding cytotoxic T-lymphocyte–associated protein 4) and 10 other loci. Conclusions: Our data show significant associations between primary biliary cirrhosis and common genetic variants at the HLA class II, IL12A, and IL12RB2 loci and suggest that the interleukin-12 immunoregulatory signaling axis is relevant to the pathophysiology of primary biliary cirrhosis. (ClinicalTrials.gov number, NCT00242125.) N Engl J Med 2009;360:2544-55. [ABSTRACT FROM AUTHOR]

Background and Aims: Routine serologic testing for celiac disease (CD) may be useful in irritable bowel syndrome (IBS) patients, but this is controversial. We aimed to compare the prevalence of unrecognized CD in a large cohort of patients with and without IBS., Participants and Methods: This is a family case-control IBS study conducted at a single US academic medical center. Stored serum and DNA were available. Tissue transglutaminase (TTg) immunoglobulin A was performed, followed by indirect immunofluorescence testing for endomysial antibodies with positive or weakly positive TTg results. Individuals were considered to have CD if both results were positive. χ and Fisher's exact tests were used to compare prevalence between the two groups., Results: Serum samples were studied from 533 cases and 531 controls. In all, 80% of participants were female, with a median age of 50 years; 65% of cases and 0% controls met the Rome criteria for IBS. Previous serological testing for CD had occurred in 142 (27%) cases and 13 (2%) controls, but none had CD on subsequent testing. Six (1.1%) cases versus five (0.9%) controls had positive or weakly positive TTg test. Six cases (1.1%) versus three (0.6%) controls were confirmed to have CD by endomysial antibody (P=0.51)., Conclusion: No difference in the prevalence of CD between patients with IBS and patients without IBS at a tertiary medical center was observed. Our findings do not support routine celiac serologic or genetic testing in patients with IBS in all US populations.

Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as 'rib fractures', where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.

Background: Primary biliary cirrhosis is a cholestatic liver disease characterized by immune-mediated destruction of bile ducts. Its pathogenesis is largely unknown, although complex interactions between environment and genetic predisposition are proposed., Aims: Identify disease risk factors using a detailed patient questionnaire and compare study findings to 3 published reports., Methods: Questionnaire data were prospectively collected from 522 cases and 616 controls of the Mayo Clinic Primary Biliary Cirrhosis Genetic Epidemiology Registry. Case and control responses were compared using logistic regression, adjusting for recruitment age, sex, and education level., Results: Cases reported ever regularly smoking cigarettes more frequently than controls (P < 0.001). History of urinary tract infection was similar between groups; however, cases reported multiple urinary tract infections more commonly than controls (P < 0.001). Frequency of other autoimmune disease was higher in cases than controls (P < 0.001). As well, prevalence of primary biliary cirrhosis among first-degree relatives was higher in case families than control families (P < 0.001)., Conclusions: Our study confirms prior reported risk factors associated with disease risk. Given the potential importance of gene and environment interactions, further examination of environmental risk factors considering genetic background may provide new insight into primary biliary cirrhosis pathogenesis., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Interferon (IFN) gamma (IFNG) allelic variants are associated with susceptibility to multiple sclerosis (MS) in men but not in women., Objectives: To conduct a high-density linkage disequilibrium association study of IFNG and the surrounding region for sex-associated MS susceptibility bias and to evaluate whether IFNG allelic variants associated with MS susceptibility are associated with expression., Design: Genotype case-control study, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay expression analyses for IFN gamma., Setting: Three independently ascertained populations from the Mayo Clinic, Rochester, Minnesota, Queen's University of Belfast, Belfast, Ireland, and University of Leuven, Leuven, Belgium., Patients: For linkage disequilibrium, 861 patients with MS (293 men and 568 women) and 843 controls (340 men and 503 women) derived from the US (population-based) and the Northern Ireland and Belgium (clinic-based) cohorts were studied. For expression analyses, 50 US patients were selected to enrich for homozygotes and to achieve a balance between men and women., Interventions: Twenty markers were genotyped over the 120-kilobase region harboring IFNG and the interleukin 26 gene (IL26)., Main Outcome Measures: Expression of IFN gamma was evaluated by qPCR and enzyme-linked immunosorbent assay in stimulated peripheral blood mononuclear cells., Results: Multiple markers were associated with MS susceptibility in men but not in women. The sex-specific susceptibility markers, of which rs2069727 was the strongest, were confined to IFNG. Carriers of rs2069727*G had higher expression than noncarriers. The effect of genotype in the qPCR experiments was also evident in men but not in women., Conclusions: IFNG is associated with sex bias in MS susceptibility and with expression of IFN gamma in MS. These observations add to a growing body of literature that implicates an interaction between sex and IFN gamma expression in a variety of disease states.