Showing papers by "Rush University Medical Center published in 2007"

Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer

Abstract: vs. 0.0%, P<0.001), proteinuria (3.6% vs. 0.0%, P<0.001), headache (2.2% vs. 0.0%, P = 0.008), and cerebrovascular ischemia (1.9% vs. 0.0%, P = 0.02) were more frequent in patients receiving paclitaxel plus bevacizumab. Infection was more common in patients receiving paclitaxel plus bevacizumab (9.3% vs. 2.9%, P<0.001), but febrile neutropenia was uncommon (<1% overall). Conclusions Initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab prolongs progression-free survival, but not overall survival, as compared with paclitaxel alone. (ClinicalTrials.gov number, NCT00028990.)

Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship

Abstract: Timothy H. Dellit, Robert C. Owens, John E. McGowan, Jr., Dale N. Gerding, Robert A. Weinstein, John P. Burke, W. Charles Huskins, David L. Paterson, Neil O. Fishman, Christopher F. Carpenter, P. J. Brennan, Marianne Billeter, and Thomas M. Hooton Harborview Medical Center and the University of Washington, Seattle; Maine Medical Center, Portland; Emory University, Atlanta, Georgia; Hines Veterans Affairs Hospital and Loyola University Stritch School of Medicine, Hines, and Stroger (Cook County) Hospital and Rush University Medical Center, Chicago, Illinois; University of Utah, Salt Lake City; Mayo Clinic College of Medicine, Rochester, Minnesota; University of Pittsburgh Medical Center, Pittsburgh, and University of Pennsylvania, Philadelphia, Pennsylvania; William Beaumont Hospital, Royal Oak, Michigan; Ochsner Health System, New Orleans, Louisiana; and University of Miami, Miami, Florida

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Abstract: Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.

Mixed brain pathologies account for most dementia cases in community-dwelling older persons

Abstract: Objective: To examine the spectrum of neuropathology in persons from the Rush Memory and Aging Project, a longitudinal community-based clinical-pathologic cohort study. Methods: The study includes older persons who agreed to annual clinical evaluation and brain donation. We examined the neuropathologic diagnoses, including Alzheimer disease (AD) (NIA-Reagan Criteria), cerebral infarctions, and Parkinson disease/Lewy body disease (PD/LBD), in the first 141 autopsies. We calculated the frequency of each diagnosis alone and mixed diagnoses. We used logistic regression to compare one to multiple diagnoses on the odds of dementia. Results: Twenty persons (14.2%) had no acute or chronic brain abnormalities. The most common chronic neuropathologic diagnoses were AD (n = 80), cerebral infarctions (n = 52), and PD/LBD (n = 24). In persons with dementia (n = 50), 38.0% (n = 19) had AD and infarcts, 30.0% (n = 15) had pure AD, and 12% each had vascular dementia (n = 6) and AD with PD/LBD (n = 6). In those without dementia (n = 91), 28.6% (n = 26) had no chronic diagnostic abnormalities, 24.2% (n = 22) had pure AD, and 17.6% (n = 16) had infarctions. In persons with dementia, over 50% had multiple diagnoses (AD, PD/LBD, or infarcts), whereas, in persons without dementia, over 80% had one or no diagnosis. After accounting for age, persons with multiple diagnoses were almost three times (OR = 2.8; 95% CI = 1.2, 6.7) more likely to exhibit dementia compared to those with one pathologic diagnosis. Conclusion: The majority of community-dwelling older persons have brain pathology. Those with dementia most often have multiple brain pathologies, which greatly increases the odds of dementia.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

Abstract: This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Loneliness and Risk of Alzheimer Disease

Abstract: Context Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. Objective To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD). Design Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. Participants A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions. Main outcome measures Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions. Results During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction. Conclusion Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A scientific statement from the American Heart Association and the American Diabetes Association

Abstract: The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration

Abstract: The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for Frontotemporal Lobar Degeneration and experts at other centers to review and revise the existing neuropathologic diagnostic criteria for FTLD. The proposed criteria for FTLD are based on existing criteria, which include the tauopathies [FTLD with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, sporadic multiple system tauopathy with dementia, argyrophilic grain disease, neurofibrillary tangle dementia, and FTD with microtubule-associated tau (MAPT) gene mutation, also called FTD with parkinsonism linked to chromosome 17 (FTDP-17)]. The proposed criteria take into account new disease entities and include the novel molecular pathology, TDP-43 proteinopathy, now recognized to be the most frequent histological finding in FTLD. TDP-43 is a major component of the pathologic inclusions of most sporadic and familial cases of FTLD with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Molecular genetic studies of familial cases of FTLD-U have shown that mutations in the progranulin (PGRN) gene are a major genetic cause of FTLD-U. Mutations in valosin-containing protein (VCP) gene are present in rare familial forms of FTD, and some families with FTD and/or MND have been linked to chromosome 9p, and both are types of FTLD-U. Thus, familial TDP-43 proteinopathy is associated with defects in multiple genes, and molecular genetics is required in these cases to correctly identify the causative gene defect. In addition to genetic heterogeneity amongst the TDP-43 proteinopathies, there is also neuropathologic heterogeneity and there is a close relationship between genotype and FTLD-U subtype. In addition to these recent significant advances in the neuropathology of FTLD-U, novel FTLD entities have been further characterized, including neuronal intermediate filament inclusion disease. The proposed criteria incorporate up-to-date neuropathology of FTLD in the light of recent immunohistochemical, biochemical, and genetic advances. These criteria will be of value to the practicing neuropathologist and provide a foundation for clinical, clinico-pathologic, mechanistic studies and in vivo models of pathogenesis of FTLD.

Diagnostic procedures for Parkinson's disease dementia: Recommendations from the movement disorder society task force

Abstract: A preceding article described the clinical features of Parkinson's disease dementia (PD-D) and proposed clinical diagnostic criteria for "probable" and "possible" PD-D. The main focus of this article is to operationalize the diagnosis of PD-D and to propose practical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time-consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD-D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD-D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence-based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.

A Meta-analysis of the Incidence of Anterior Cruciate Ligament Tears as a Function of Gender, Sport, and a Knee Injury–Reduction Regimen

Abstract: Purpose: The literature has shown that anterior cruciate ligament (ACL) tear rates vary by gender, by sport, and in response to injury-reduction training programs. However, there is no consensus as to the magnitudes of these tear rates or their variations as a function of these variables. For example, the female-male ACL tear ratio has been reported to be as high as 9:1. Our purpose was to apply meta-analysis to the entire applicable literature to generate accurate estimates of the true incidences of ACL tear as a function of gender, sport, and injury-reduction training. Methods: A PubMed literature search was done to identify all studies dealing with ACL tear incidence. Bibliographic cross-referencing was done to identify additional articles. Meta-analytic principles were applied to generate ACL incidences as a function of gender, sport, and prior injury-reduction training. Results: Female-male ACL tear incidences ratios were as follows: basketball, 3.5; soccer, 2.67; lacrosse, 1.18; and Alpine skiing, 1.0. The collegiate soccer tear rate was 0.32 for female subjects and 0.12 for male subjects. For basketball, the rates were 0.29 and 0.08, respectively. The rate for recreational Alpine skiers was 0.63, and that for experts was 0.03, with no gender variance. The two volleyball studies had no ACL tears. Training reduced the ACL tear incidence in soccer by 0.24 but did not reduce it at all in basketball. Conclusions: Female subjects had a roughly 3 times greater incidence of ACL tears in soccer and basketball versus male subjects. Injury-reduction programs were effective for soccer but not basketball. Recreational Alpine skiers had the highest incidences of ACL tear, whereas expert Alpine skiers had the lowest incidences. Volleyball may in fact be a low-risk sport rather than a high-risk sport. Alpine skiers and lacrosse players had no gender difference for ACL tear rate. Year-round female athletes who play soccer and basketball have an ACL tear rate of approximately 5%. Level of Evidence: Level IV, therapeutic case series.

Depression Rating Scales in Parkinson’s Disease: Critique and Recommendations

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

The National Alzheimer's Coordinating Center (NACC) database: the Uniform Data Set.

Abstract: The National Alzheimer's Coordinating Center (NACC) is responsible for developing and maintaining a database of participant information collected from the 29 Alzheimer's Disease Centers (ADCs) funded by the National Institute on Aging (NIA). The NIA appointed the ADC Clinical Task Force to determine and define an expanded, standardized clinical data set, called the Uniform Data Set (UDS). The goal of the UDS is to provide ADC researchers a standard set of assessment procedures, collected longitudinally, to better characterize ADC participants with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented controls. NACC implemented the UDS (September 2005) by developing data collection forms for initial and follow-up visits based on Clinical Task Force definitions, a relational database, and a data submission system accessible by all ADCs. The NIA requires ADCs to submit UDS data to NACC for all their Clinical Core participants. Thus, the NACC web site (https://www.alz.washington.edu) was enhanced to provide efficient and secure access data submission and retrieval systems.

DLB and PDD boundary issues: Diagnosis, treatment, molecular pathology, and biomarkers

Abstract: For more than a decade, researchers have refined criteria for the diagnosis of dementia with Lewy bodies (DLB) and at the same time have recognized that cognitive impairment and dementia occur commonly in patients with Parkinson disease (PD). This article addresses the relationship between DLB, PD, and PD with dementia (PDD). The authors agreed to endorse "Lewy body disorders" as the umbrella term for PD, PDD, and DLB, to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of alpha-synuclein metabolism. We concluded that the differing temporal sequence of symptoms and clinical features of PDD and DLB justify distinguishing these disorders. However, a single Lewy body disorder model was deemed more useful for studying disease pathogenesis because abnormal neuronal alpha-synuclein inclusions are the defining pathologic process common to both PDD and DLB. There was consensus that improved understanding of the pathobiology of alpha-synuclein should be a major focus of efforts to develop new disease-modifying therapies for these disorders. The group agreed on four important priorities: 1) continued communication between experts who specialize in PDD or DLB; 2) initiation of prospective validation studies with autopsy confirmation of DLB and PDD; 3) development of practical biomarkers for alpha-synuclein pathologies; 4) accelerated efforts to find more effective treatments for these diseases.

TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions.

Abstract: TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND) Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND On selected cases, immunoelectron microscopy and biochemistry were performed Clinically defined frontotemporal dementias (FTDs) included four groups: 1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5), charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2) familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72); and 4) familial and sporadic FTD with MND (n = 40) Our studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations Thus, despite significant clinical, genetic, and neuropathological heterogeneity of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD pathogenesis

Levodopa-induced dyskinesias.

Abstract: Levodopa-induced dyskinesias (LID) are common and difficult to treat. This review focuses on three issues related to LID: clinical features, classification and rating, pathophysiology and pathogenesis, and management. The three primary clinical syndromes are OFF-period dystonia, peak-dose dyskinesia, and diphasic dyskinesia. Several other forms also occur, making the evaluation and choice of treatment complicated. A core component of the pathophysiology of LID is overactivity of the direct striatal output pathway. This pathway provides a direct GABAergic connection by which the striatum inhibits the output regions of the basal ganglia, i.e., the internal globus pallidus and the substantia nigra pars reticulata. Altering dopaminergic dosing and timing can abate dyskinesias, but usually impact the control of parkinsonism. Putative therapies to reduce the problem of dyskinesias could focus on the glutamatergic, GABAergic, alpha2 adrenergic, serotonergic (5HT1A, 5HT2A), opioid, histamine H3, adenosine A2A receptors, the monoamine transport or cannabinoid CB1 receptors systems. The only currently available drug with an evidence-based recommendation on efficacy for dyskinesia is amantadine. Therapy goals include the prevention of dyskinesia and treatment of dyskinesias that are troublesome clinically. New rating measures to assess severity and disability related to dyskinesia are in the process of development and clinimetric testing.

Diagnostic criteria for psychosis in Parkinson's disease: Report of an NINDS, NIMH work group

Abstract: There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we pro- pose provisional criteria for PDPsy in the style of the Diagnos- tic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallu- cinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psycho- sis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospa- tial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxica- tion. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic cri- teria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and con- This article is part of the journal's CME program. The CME form can be found on page 1214 and is available online at http://www.

Obesity and spine surgery: relation to perioperative complications

Abstract: Object Many patients undergoing elective thoracic or lumbar fusion procedures are obese, but the contribution of obesity to complications in spine surgery has not been defined. The authors retrospectively assessed the prevalence of obesity in a cohort of patients undergoing thoracic and lumbar fusion and correlate the presence of obesity with the incidence of operative complications. Methods A retrospective review of consecutive patients treated by a single surgeon (J.K.R.) over a 36-month period at either Rush University Medical Center or the Neurological and Orthopedic Institute of Chicago was performed. The authors identified 332 elective thoracic and lumbar spine surgery cases; the cohort was restricted to include only patients with symptomatic degenerative conditions in need of an anterior, posterior, or combined anterior–posterior fusion. Cases of trauma, tumor, and infection and any case in which the procedure was performed for emergency indications were excluded. A total of 97 cases were identifie...

Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. The present study evaluates the ability of peptide corresponding to the NF-κB essential modifier-binding domain (NBD) of IκB kinase α (IKKα) or IKKβ to prevent nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and establish a role for NF-κB in human parkinsonism. First, we found that NF-κB was activated within the substantia nigra pars compacta of PD patients and MPTP-intoxicated mice. However, i.p. injection of wild-type NBD peptide reduced nigral activation of NF-κB, suppressed nigral microglial activation, protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in MPTP-intoxicated mice. These findings were specific because mutated NBD peptide had no effect. We conclude that selective inhibition of NF-κB activation by NBD peptide may be of therapeutic benefit for PD patients.

Prescribing Amiodarone: An Evidence-Based Review of Clinical Indications

Abstract: ContextAlthough amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed antiarrhythmic medications in the United States.ObjectiveTo evaluate and synthesize evidence regarding optimal use of amiodarone for various arrhythmias.Evidence AcquisitionSystematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. The search was limited to human-participant, English-language reports published between 1970 and 2007. Amiodarone was searched using the terms adverse effects, atrial fibrillation, atrial flutter, congestive heart failure, electrical storm, hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, surgery, ventricular arrhythmia, ventricular fibrillation, and Wolff-Parkinson-White. Bibliographies of identified articles and guidelines from official societies were reviewed for additional references. Ninety-two identified studies met inclusion criteria and were included in the review.Evidence SynthesisAmiodarone may have clinical value in patients with left ventricular dysfunction and heart failure as first-line treatment for atrial fibrillation, though other agents are available. Amiodarone is useful in acute management of sustained ventricular tachyarrythmias, regardless of hemodynamic stability. The only role for prophylactic amiodarone is in the perioperative period of cardiac surgery. Amiodarone may be effective as an adjunct to implantable cardioverter-defibrillator therapy to reduce number of shocks. However, amiodarone has a number of serious adverse effects, including corneal microdeposits (>90%), optic neuropathy/neuritis (≤1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, <3% [0.6% annually]).ConclusionAmiodarone should be used with close follow-up in patients who are likely to derive the most benefit, namely those with atrial fibrillation and left ventricular dysfunction, those with acute sustained ventricular arrhythmias, those about to undergo cardiac surgery, and those with implantable cardioverter-defibrillators and symptomatic shocks.

Safety considerations with fibrate therapy.

Abstract: Fibrates are an important class of drugs for the management of dyslipidemia. This class of drugs is generally well tolerated but is infrequently associated with several safety issues. Fibrates, most likely by an effect mediated by peroxisome proliferator-activated receptor–α, may reversibly increase creatinine and homocysteine but are not associated with an increased risk for renal failure in clinical trials. Fibrates are associated with a slightly increased risk (

Frailty is associated with incident Alzheimer's disease and cognitive decline in the elderly.

Abstract: Objective:To assess the association between frailty and incident Alzheimer’s disease (AD) and cognitive decline. Frailty is common in older persons and associated with adverse health outcomes.Methods:Study subjects included 823 older persons without dementia who participated in the Rush Memory and A

Relation of cognitive activity to risk of developing Alzheimer disease

Abstract: Background: Frequent cognitive activity in old age has been associated with reduced risk of Alzheimer disease (AD), but the basis of the association is uncertain. Methods: More than 700 old people underwent annual clinical evaluations for up to 5 years. At baseline, they rated current and past frequency of cognitive activity with the current activity measure administered annually thereafter. Those who died underwent a uniform postmortem examination of the brain. Amyloid burden, density of tangles, and presence of Lewy bodies were assessed in eight brain regions and the number of chronic cerebral infarctions was noted. Results: During follow-up, 90 people developed AD. More frequent participation in cognitive activity was associated with reduced incidence of AD (HR 0.58; 95% CI: 0.44, 0.77); a cognitively inactive person (score 2.2, 10th percentile) was 2.6 times more likely to develop AD than a cognitively active person (score 4.0, 90th percentile). The association remained after controlling for past cognitive activity, lifespan socioeconomic status, current social and physical activity, and low baseline cognitive function. Frequent cognitive activity was also associated with reduced incidence of mild cognitive impairment and less rapid decline in cognitive function. Among 102 persons who died and had a brain autopsy, neither global nor regionally specific measures of neuropathology were related to level of cognitive activity before the study, at study onset, or during the course of the study. Conclusion: Level of cognitively stimulating activity in old age is related to risk of developing