Showing papers by "Tufts University published in 2007"
TL;DR: The prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994 and this increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications.
Abstract: ContextThe prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence of earlier stages of chronic kidney disease (CKD) during this period is uncertain.ObjectiveTo update the estimated prevalence of CKD in the United States.Design, Setting, and ParticipantsCross-sectional analysis of the most recent National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004), a nationally representative sample of noninstitutionalized adults aged 20 years or older in 1988-1994 (n = 15 488) and 1999-2004 (n = 13 233).Main Outcome MeasuresChronic kidney disease prevalence was determined based on persistent albuminuria and decreased estimated glomerular filtration rate (GFR). Persistence of microalbuminuria (>30 mg/g) was estimated from repeat visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation reexpressed to standard serum creatinine.ResultsThe prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004. The prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988-1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI, 1.2-1.4). The prevalence estimates of CKD stages in 1988-1994 and 1999-2004, respectively, were 1.7% (95% CI, 1.3%-2.2%) and 1.8% (95% CI, 1.4%-2.3%) for stage 1; 2.7% (95% CI, 2.2%-3.2%) and 3.2% (95% CI, 2.6%-3.9%) for stage 2; 5.4% (95% CI, 4.9%-6.0%) and 7.7% (95% CI, 7.0%-8.4%) for stage 3; and 0.21% (95% CI, 0.15%-0.27%) and 0.35% (0.25%-0.45%) for stage 4. A higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased GFR. Estimation of GFR from serum creatinine has limited precision and a change in mean serum creatinine accounted for some of the increased prevalence of CKD.ConclusionsThe prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994. This increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications of CKD.
4,567 citations
TL;DR: This study predicts the burden of incident osteoporosis‐related fractures and costs in the United States, by sex, age group, race/ethnicity, and fracture type, from 2005 to 2025.
Abstract: This study predicts the burden of incident osteoporosis-related fractures and costs in the United States, by sex, age group, race/ethnicity, and fracture type, from 2005 to 2025. Total fractures were >2 million, costing nearly $17 billion in 2005. Men account for >25% of the burden. Rapid growth in the disease burden is projected among nonwhite populations.
Introduction: The aging of the U.S. population will likely lead to greater prevalence of osteoporosis. Policy makers require precise projections of the disease burden by demographic subgroups and skeletal sites to effectively target osteoporosis intervention and treatment programs.
Materials and Methods: A state transition Markov decision model was used to estimate total incident fractures and costs by age, sex, race/ethnicity, and skeletal site for the U.S. population ≥50 years of age for 2005–2025.
Results: More than 2 million incident fractures at a cost of $17 billion are predicted for 2005. Total costs including prevalent fractures are more than $19 billion. Men account for 29% of fractures and 25% of costs. Total incident fractures by skeletal site were vertebral (27%), wrist (19%), hip (14%), pelvic (7%), and other (33%). Total costs by fracture type were vertebral (6%), hip (72%), wrist (3%), pelvic (5%), and other (14%). By 2025, annual fractures and costs are projected to rise by almost 50%. The most rapid growth is estimated for people 65–74 years of age, with an increase >87%. An increase of nearly 175% is projected for Hispanic and other subpopulations.
Conclusions: Osteoporosis prevention, treatment, and education efforts should address all skeletal sites, not just hip and vertebral, and appropriate attention is warranted for men and diverse race/ethnicity subgroups.
3,402 citations
TL;DR: The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adult's aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for Older adults at risk of falls.
Abstract: OBJECTIVE: To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults PARTICIPANTS: A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology EVIDENCE: The expert panel reviewed existing consensus statements and relevant evidence from primary research articles and reviews of the literature Process: After drafting a recommendation for the older adult population and reviewing drafts of the Updated Recommendation from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) for Adults, the panel issued a final recommendation on physical activity for older adults SUMMARY: The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adult's aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for older adults at risk of falls In addition, older adults should have an activity plan for achieving recommended physical activity that integrates preventive and therapeutic recommendations The promotion of physical activity in older adults should emphasize moderate-intensity aerobic activity, muscle-strengthening activity, reducing sedentary behavior, and risk management Language: en
3,274 citations
TL;DR: The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.
2,391 citations
TL;DR: Silks are fibrous proteins with remarkable mechanical properties produced in fiber form by silkworms and spiders that are biocompatible when studied in vitro and in vivo.
2,236 citations
TL;DR: The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adult's aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for Older adults at risk of falls.
Abstract: Objective:To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults.Participants:A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology.Evidence:T
1,720 citations
TL;DR: When the calibration of S(cr) methods is traceable to the S( Cr) reference system, GFR should be estimated using the MDRD Study equation that has been reexpressed for standardized S(Cr).
Abstract: Purpose: We sought to reexpress the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation for estimation of glomerular filtration rate (GFR) using serum creatinine (Scr) standardized to reference methods.
Methods: Serum specimens included creatinine reference materials prepared by the College of American Pathologists (CAP), traceable to primary reference material at the NIST, with assigned values traceable to isotope dilution mass spectrometry (IDMS), a calibration panel prepared by the Cleveland Clinic Research Laboratory (CCRL), and frozen samples from the MDRD Study. Split specimens were measured at the CCRL using the Roche enzymatic and Beckman CX3 kinetic alkaline picrate assays.
Results: Roche enzymatic assay results on CAP samples were comparable to IDMS-assigned values. Beckman CX3 assay results in 2004–2005 were significantly higher than but highly correlated with simultaneous Roche enzymatic assay results ( r 2 = 0.9994 on 40 CCRL samples) and showed minimal but significant upward drift from Beckman CX3 assay results during the MDRD Study in 1989–1991 ( r 2 = 0.9987 in 253 samples). Combining these factors, standardized Scr = 0.95 × original MDRD Study Scr. The reexpressed 4-variable MDRD Study equation for Scr (mg/dL) is GFR = 175 × standardized Scr−1.154 × age−0.203 × 1.212 (if black) × 0.742 (if female), and for Scr (μmol/L) is GFR = 30849× standardized Scr−1.154 × age−0.203 × 1.212 (if black) × 0.742 (if female) [GFR in mL · min−1 · (1.73 m2)−1].
Conclusion: When the calibration of Scr methods is traceable to the Scr reference system, GFR should be estimated using the MDRD Study equation that has been reexpressed for standardized Scr.
1,681 citations
TL;DR: A multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected eosinophilic esophagitis (EE) provided current recommendations for care of affected patients.
1,513 citations
TL;DR: The intrinsic mechanisms not commonly specified by mobile elements, such as efflux pumps that expel multiple kinds of antibiotics, are now recognized as major contributors to multidrug resistance in bacteria.
1,446 citations
TL;DR: Tolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure-related morbidity.
Abstract: ContextVasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure.ObjectiveTo investigate the effects of tolvaptan initiated in patients hospitalized with heart failure.Design, Setting, and ParticipantsThe Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment.InterventionWithin 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy.Main Outcome MeasuresDual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema.ResultsDuring a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P<.001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.ConclusionTolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure–related morbidity.Trial Registrationclinicaltrials.gov Identifier: NCT00071331Published online March 25, 2007 (doi:10.1001/jama.297.12.1319).
1,378 citations
TL;DR: The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation, and the V-ATPases represent attractive and potentially highly specific drug targets.
Abstract: The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation. At the heart of regulating acidity are the vacuolar (V-)ATPases--large, multisubunit complexes that function as ATP-driven proton pumps. Their activity is controlled by regulating the assembly of the V-ATPase complex or by the dynamic regulation of V-ATPase expression on membrane surfaces. The V-ATPases have been implicated in a number of diseases and, coupled with their complex isoform composition, represent attractive and potentially highly specific drug targets.
TL;DR: These studies have shown how, for many RNA-binding proteins, multiple modules define the fundamental structural unit that is responsible for biological function.
Abstract: Many RNA-binding proteins have modular structures and are composed of multiple repeats of just a few basic domains that are arranged in various ways to satisfy their diverse functional requirements. Recent studies have investigated how different modules cooperate in regulating the RNA-binding specificity and the biological activity of these proteins. They have also investigated how multiple modules cooperate with enzymatic domains to regulate the catalytic activity of enzymes that act on RNA. These studies have shown how, for many RNA-binding proteins, multiple modules define the fundamental structural unit that is responsible for biological function.
TL;DR: It is likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system and that developmental effects occur in theFemale reproductive system.
TL;DR: A functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression is demonstrated for the first time and selected microRNAs decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation.
Abstract: Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.
TL;DR: Recent findings regarding the mechanisms of protection in helminth infections that have been elucidated in murine models are examined and the implications of these findings in terms of future therapies are discussed.
Abstract: Important insights have recently been gained in our understanding of how host immune responses mediate resistance to parasitic helminths and control associated pathological responses. Although similar cells and cytokines are evoked in response to infection by helminths as diverse as nematodes and schistosomes, the components of the response that mediate protection are dependent on the particular parasite. In this Review, we examine recent findings regarding the mechanisms of protection in helminth infections that have been elucidated in murine models and discuss the implications of these findings in terms of future therapies.
TL;DR: Hospitals engaged in both public reporting and pay for performance achieved modestly greater improvements in quality than did hospitals engaged only in public reporting.
Abstract: BACKGROUND Public reporting and pay for performance are intended to accelerate improvements in hospital care, yet little is known about the benefits of these methods of providing incentives for improving care. METHODS We measured changes in adherence to 10 individual and 4 composite measures of quality over a period of 2 years at 613 hospitals that voluntarily reported information about the quality of care through a national public-reporting initiative, including 207 facilities that simultaneously participated in a pay-for-performance demonstration project funded by the Centers for Medicare and Medicaid Services; we then compared the pay-for-performance hospitals with the 406 hospitals with public reporting only (control hospitals). We used multivariable modeling to estimate the improvement attributable to financial incentives after adjusting for baseline performance and other hospital characteristics. RESULTS As compared with the control group, pay-for-performance hospitals showed greater improvement in all composite measures of quality, including measures of care for heart failure, acute myocardial infarction, and pneumonia and a composite of 10 measures. Baseline performance was inversely associated with improvement; in pay-for-performance hospitals, the improvement in the composite of all 10 measures was 16.1% for hospitals in the lowest quintile of baseline performance and 1.9% for those in the highest quintile (P<0.001). After adjustments were made for differences in baseline performance and other hospital characteristics, pay for performance was associated with improvements ranging from 2.6 to 4.1% over the 2-year period. CONCLUSIONS Hospitals engaged in both public reporting and pay for performance achieved modestly greater improvements in quality than did hospitals engaged only in public reporting. Additional research is required to determine whether different incentives would stimulate more improvement and whether the benefits of these programs outweigh their costs.
TL;DR: In middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors.
Abstract: Background—Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals. Methods and Results—We related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of 3o f the following: waist circumference 35 inches (women) or 40 inches (men); fasting blood glucose 100 mg/dL; serum triglycerides 150 mg/dL; blood pressure 135/85 mm Hg; and high-density lipoprotein cholesterol 40 mg/dL (men) or 50 mg/dL (women). Multivariable models included adjustments for age, sex, physical activity, smoking, dietary intake of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Cross-sectionally, individuals consuming 1 soft drink per day had a higher prevalence of metabolic syndrome (odds ratio [OR], 1.48; 95% CI, 1.30 to 1.69) than those consuming 1 drink per day. On follow-up (mean of 4 years), new-onset metabolic syndrome developed in 765 (18.7%) of 4095 participants consuming 1 drink per day and in 474 (22.6%) of 2059 persons consuming 1 soft drink per day. Consumption of 1 soft drink per day was associated with increased odds of developing metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74), obesity (OR, 1.31; 95% CI, 1.02 to 1.68), increased waist circumference (OR, 1.30; 95% CI, 1.09 to 1.56), impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48), higher blood pressure (OR, 1.18; 95% CI, 0.96 to 1.44), hypertriglyceridemia (OR, 1.25; 95% CI, 1.04 to 1.51), and low high-density lipoprotein cholesterol (OR, 1.32; 95% CI 1.06 to 1.64). Conclusions—In middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors. (Circulation. 2007;116:480-488.)
TL;DR: It is becoming clear that the peculiar structures of repeat-containing transcripts are at the heart of the pathogenesis of these diseases, and the presence of expanded DNA repeats alters gene expression in human cells, leading to disease.
Abstract: Nearly 30 hereditary disorders in humans result from an increase in the number of copies of simple repeats in genomic DNA. These DNA repeats seem to be predisposed to such expansion because they have unusual structural features, which disrupt the cellular replication, repair and recombination machineries. The presence of expanded DNA repeats alters gene expression in human cells, leading to disease. Surprisingly, many of these debilitating diseases are caused by repeat expansions in the non-coding regions of their resident genes. It is becoming clear that the peculiar structures of repeat-containing transcripts are at the heart of the pathogenesis of these diseases.
TL;DR: This review is a detailed review of published studies that have focused on the mechanistic basis of BPA action in diverse experimental models and an assessment of the strength of the evidence regarding the published BPA research.
TL;DR: In a survey of meta-analyses, the authors found that only 7% to 18% of the articles that employed funnel-plot asymmetry tests were significant in 7%-18% of them.
Abstract: Background: Statistical tests for funnel-plot asymmetry are common in meta-analyses. Inappropriate application can generate misleading inferences about publication bias. We aimed to measure, in a survey of meta-analyses, how frequently the application of these tests would be not meaningful or inappropriate. Methods: We evaluated all meta-analyses of binary outcomes with e 3 studies in the Cochrane Database of Systematic Reviews (2003, issue 2). A separate, restricted analysis was confined to the largest meta-analysis in each of the review articles. In each meta-analysis, we assessed whether criteria to apply asymmetry tests were met: no significant heterogeneity, I2 4. We performed a correlation and 2 regression asymmetry tests and evaluated their concordance. Finally, we sampled 60 meta-analyses from print journals in 2005 that cited use of the standard regression test. Results: A total of 366 of 6873 (5%) and 98 of 846 meta-analyses (12%) in the wider and restricted Cochrane data set, respectively, would have qualified for use of asymmetry tests. Asymmetry test results were significant in 7%–18% of the meta-analyses. Concordance between the 3 tests was modest (estimated k 0.33–0.66). Of the 60 journal meta-analyses, 7 (12%) would qualify for asymmetry tests; all 11 claims for identification of publication bias were made in the face of large and significant heterogeneity. Interpretation: Statistical conditions for employing asymmetry tests for publication bias are absent from most meta-analyses; yet, in medical journals these tests are performed often and interpreted erroneously.
TL;DR: This paper provides a comprehensive review of the recent studies that have demonstrated P600s to semantic violations in light of several proposed triggers, and suggests that normal language comprehension proceeds along at least two competing neural processing streams: a semantic memory-based mechanism, and a combinatorial mechanism that assigns structure to a sentence primarily on the basis of morphosyntactic rules, but also on the based of certain semantic-thematic constraints.
Mayo Clinic1, Tufts University2, University of Alabama at Birmingham3, University of Rochester4, University of Münster5, University of Bologna6, University of Bari7, Memorial Hospital of South Bend8, University of Naples Federico II9, Complutense University of Madrid10, Mount Sinai St. Luke's and Mount Sinai Roosevelt11, University of Padua12, Royal Prince Alfred Hospital13
TL;DR: In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm.
Abstract: ContextRecently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved.ObjectiveTo study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM.Design, Setting, and PatientsMulticenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.Main Outcome MeasureAppropriate ICD intervention terminating ventricular tachycardia or fibrillation.ResultsThe 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%).ConclusionsIn a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.
TL;DR: More effective treatments are needed in the future for prevention and treatment of exacerbations of chronic obstructive pulmonary disease and there are presently no reliable biomarkers with which to predict exacerbations.
Abstract: Exacerbations of chronic obstructive pulmonary disease are of major importance in terms of their prolonged detrimental effects on patients, the acceleration in disease progression and high healthcare costs. There is still debate about how exacerbations should be defined and graded, and their mechanisms are poorly understood. The major causal agents are either bacteria or viral infections, or a combination of the two. Noninfective causes include air pollution and pulmonary embolus but, in some patients, no cause is identified. Exacerbations represent an increase in the inflammation that is present in the stable state, with increased numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines and proteases in the airways, and increased concentrations of certain cytokines and C-reactive protein in the blood. There are presently no reliable biomarkers with which to predict exacerbations. Exacerbations have a long-lasting adverse influence on health status. High doses of bronchodilators are the mainstay of treatment and systemic corticosteroids have some benefit. The routine use of antibiotics remains controversial but they are of benefit with exacerbations of a bacterial origin. Noninvasive ventilation is beneficial in preventing the need for intubation and its important complications but it is not certain whether its use in stable patients prevents exacerbations. Although important advances have been made, more effective treatments are needed in the future for prevention and treatment of exacerbations.
National Institutes of Health1, University of Texas MD Anderson Cancer Center2, University of Texas Health Science Center at San Antonio3, Wayne State University4, University of Virginia5, Harvard University6, Tufts University7, Emory University8, Albany Medical College9, University of Paris10, Roswell Park Cancer Institute11, Santa Clara Valley Medical Center12, University of Minnesota13, University of Maryland, Baltimore14, Merck & Co.15, Eisai16, Duke University17
TL;DR: Findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.
Abstract: Background Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. Methods We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. Results Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. Conclusions Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.
University of Toronto1, Harvard University2, University of Zurich3, Queen Mary University of London4, Tufts University5, University of California, San Diego6, Boston University7, Medical University of South Carolina8, University of Helsinki9, Queensland Health10, University of Queensland11, University of California, Riverside12, University of Auckland13, University of Saskatchewan14, Ruhr University Bochum15
TL;DR: There is now strong evidence that increasing vitamin D intake will lower risk of falling and lower fracture risk in older men and women and regulatory agencies in the United States and abroad should review the evidence and reassess their dietary recommendations.
University of Missouri1, Auburn University2, University of Cincinnati3, United States Environmental Protection Agency4, Maryville College5, University of Siena6, University of Florida7, Harvard University8, National Institutes of Health9, Washington State University10, National Institutes of Natural Sciences, Japan11, Brunel University London12, Case Western Reserve University13, University of Connecticut14, North Carolina State University15, Emory University16, Tulane University17, Universidad Miguel Hernández de Elche18, University of Granada19, University of Illinois at Chicago20, United States Geological Survey21, Tufts University22, Charité23, Carleton College24, University of Texas Medical Branch25, University of Massachusetts Amherst26
TL;DR: This document is a summary statement of the outcome from he meeting: “Bisphenol A: An Examination of the Relevance of cological, In vitro and Laboratory Animal Studies for Assessng Risks to Human Health” sponsored by both the NIEHS and IDCR at NIH/DHHS.
TL;DR: Results indicate that the behavioral and ERP measures reported here appear to be tapping into different components of the process(es) involved in semantic priming, as well as the implication for the linguistic processes underlying the N400.
Abstract: Two experiments explored the effects of stimulus degradation on behavioral and event-related potential (ERP) measures of semantic priming. The primary goal was to help elucidate the psychological processes that underlie the N400 component. In both experiments, subjects made speeded lexical decisions to words and pseudowords preceded by either semantically related or unrelated prime words. In one block of trials, the target stimuli were intact, and in a second block they were degraded by removing a random 33% of the elements making up each letter of the target (Experiment 1) or by overlaying a matrix of dots on the target (Experiment 2). In both experiments, subjects responded faster and more accurately to related targets than to unrelated targets (behavioral semantic priming effect), and this priming effect was greater when the target was degraded. However, although the N400 component was larger for unrelated than related targets (ERP semantic priming effect), there was no evidence that this difference was larger in the degraded block of either experiment. These results indicate that the behavioral and ERP measures reported here appear to be tapping into different components of the process(es) involved in semantic priming. The implication of the results for the linguistic processes underlying the N400 are discussed.
TL;DR: Retinal nerve fiber layer thickness, as measured by Stratus OCT, varies significantly with age, ethnicity, axial length, and optic disc area, and these variables may need to be taken into account when evaluating patients for diagnosis and follow-up of glaucoma.
University of Georgia1, North Carolina State University2, Washington State University3, University of Guelph4, University of California, Davis5, Ludwig Maximilian University of Munich6, Royal Veterinary College7, University of Wisconsin-Madison8, Tufts University9, University of Pennsylvania10, University of Minnesota11, University of Florida12
TL;DR: The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment.
Abstract: Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the ACVIM Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.
TL;DR: Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment of Pheochromocytoma that inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.
Abstract: Pheochromocytomas are rare, often hereditary, catecholamine producing tumors that can be difficult to diagnose and manage. This Review summarizes the recommendations for biochemical and genetic testing, localization and treatment, and is based on discussions at the First International Symposium on Pheochromocytoma, held in October 2005. The First International Symposium on Pheochromocytoma, held in October 2005, included discussions about developments concerning these rare catecholamine-producing tumors. Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment. Measurement of plasma or urinary fractionated metanephrines, the most accurate screening approach, was recommended as the first-line test for diagnosis; reference intervals should favor sensitivity over specificity. Localization studies should only follow reasonable clinical evidence of a tumor. Preoperative pharmacologic blockade of circulatory responses to catecholamines is mandatory. Because approximately a quarter of tumors develop secondary to germ-line mutations in any one of five genes, mutation testing should be considered; however, it is not currently cost effective to test every gene in every patient. Consideration of tumor location, presence of multiple tumors, presence of metastases, and type of catecholamine produced is useful in deciding which genes to test. Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.