Showing papers by "Veterans Health Administration published in 2005"

Adherence to Medication

Abstract: The full benefit of many effective medications will be achieved only if patients adhere to prescribed treatment regimens. Unfortunately, applying terms such as “noncompliant” and “nonadherent” to patients who do not consume every pill at the desired time can stigmatize them in their future relationships with health care providers. This article on medication adherence (or compliance) reviews strategies to assess and enhance this important aspect of patient care.

Diversity of the human intestinal microbial flora.

Abstract: The human endogenous intestinal microflora is an essential “organ” in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Extended-spectrum beta-lactamases: a clinical update.

Abstract: Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

Abstract: background The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella– zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. methods We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine (“zoster vaccine”). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. results More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. conclusions The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections

Abstract: EXECUTIVE SUMMARYSoft-tissue infections are common, generally of mild tomodest severity, and are easily treated with a variety ofagents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patientswith mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have beenproposed to guide the clinician [1]. However, mostclinical assessments have been developed from eitherretrospective studies or from an author’s own “clinicalexperience,” illustrating the need for prospectivestudieswith defined measurements of severity coupled to man-agement issues and outcomes.Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity (e.g.,fever or hypothermia, tachycardia [heart rate,

Natural oligomers of the amyloid-|[beta]| protein specifically disrupt cognitive function

Abstract: A central unresolved problem in research on Alzheimer disease is the nature of the molecular entity causing dementia. Here we provide the first direct experimental evidence that a defined molecular species of the amyloid-β protein interferes with cognitive function. Soluble oligomeric forms of amyloid-β, including trimers and dimers, were both necessary and sufficient to disrupt learned behavior in a manner that was rapid, potent and transient; they produced impaired cognitive function without inducing permanent neurological deficits. Although β-amyloidosis has long been hypothesized to affect cognition, the abnormally folded protein species associated with this or any other neurodegenerative disease has not previously been isolated, defined biochemically and then specifically characterized with regard to its effects on cognitive function. The biochemical isolation of discrete amyloid-β moieties with pathophysiological properties sets the stage for a new approach to studying the molecular mechanisms of cognitive impairment in Alzheimer disease and related neurodegenerative disorders.

Determinants of Long-Term Survival After Major Surgery and the Adverse Effect of Postoperative Complications

Abstract: Objective: The objective of this study was to identify the determinants of 30-day postoperative mortality and long-term survival after major surgery as exemplified by 8 common operations. Background Data: The National Surgical Quality Improvement Program (NSQIP) database contains pre-, intra-, and 30-day postoperative data, prospectively collected in a standardized fashion by a dedicated nurse reviewer, on major surgery in the Veterans Administration (VA). The Beneficiary Identification and Records Locator Subsystem (BIRLS) is a VA file that depicts the vital status of U.S. veterans with 87% to 95% accuracy. Methods: NSQIP data were merged with BIRLS to determine the vital status of 105,951 patients who underwent 8 types of operations performed between 1991 and 1999, providing an average follow up of 8 years. Logistic and Cox regression analyses were performed to identify the predictors of 30-day mortality and long-term survival, respectively. Results: The most important determinant of decreased postoperative survival was the occurrence, within 30 days postoperatively, of any one of 22 types of complications collected in the NSQIP. Independent of preoperative patient risk, the occurrence of a 30-day complication in the total patient group reduced median patient survival by 69%. The adverse effect of a complication on patient survival was also influenced by the operation type and was sustained even when patients who did not survive for 30 days were excluded from the analyses. Conclusions: The occurrence of a 30-day postoperative complication is more important than preoperative patient risk and intraoperative factors in determining the survival after major surgery in the VA. Quality and process improvement in surgery should be directed toward the prevention of postoperative complications.

Mindfulness-Based Stress Reduction for Health Care Professionals: Results From a Randomized Trial

Abstract: The literature is replete with evidence that the stress inherent in health care negatively impacts health care professionals, leading to increased depression, decreased job satisfaction, and psychological distress. In an attempt to address this, the current study examined the effects of a short-term stress management program, mindfulness-based stress reduction (MBSR), on health care professionals. Results from this prospective randomized controlled pilot study suggest that an 8-week MBSR intervention may be effective for reducing stress and increasing quality of life and self-compassion in health care professionals. Implications for future research and practice are discussed.

Cystatin C and the risk of death and cardiovascular events among elderly persons.

Abstract: Background Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community. Methods Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c). Results Higher cystatin C levels were directly associated, in a dose–response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66);...

Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease

Abstract: Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs’ Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.

Reliability of gait performance tests in men and women with hemiparesis after stroke

Abstract: Objective: To assess the reliability of 6 gait performance tests in individuals with chronic mild to moderate post-stroke hemiparesis. Design: An intra-rater (between occasions) test-retest reliability study. Subjects: Fifty men and women (mean age 58 6.4 years) 6–46 months post-stroke. Methods: The Timed “Up & Go” test, the Comfortable and the Fast Gait Speed tests, the Stair Climbing ascend and descend tests and the 6-Minute Walk test were assessed 7 days apart. Reliability was evaluated with the intraclass correlation coefficient (ICC 2,1), the Bland & Altman analysis, the standard error of measurement (SEM and SEM%) and the smallest real difference (SRD and SRD%). Results: Test-retest agreements were high (ICC2,1 0.94–0.99) with no discernible systematic differences between the tests. The standard error of measurement (SEM%), representing the smallest change that indicates a real (clinical) improvement for a group of individuals, was small (9%). The smallest real difference (SRD%), representing the smallest change that indicates a real (clinical) improvement for a single individual, was also small (13–23%). Conclusion: These commonly used gait performance tests are highly reliable and can be recommended to evaluate improvements in various aspects of gait performance in individuals with chronic mild to moderate hemiparesis after stroke.

A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease

Abstract: Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.

Measuring diagnoses: ICD code accuracy.

Abstract: Nosology (the systematic classification of diseases) has always fascinated the sick and their would-be healers. Western societies developed an interest in nosology in the seventeenth and eighteenth centuries when they began to track the causes of sickness and death among their citizens. In the twentieth century, when medical insurance programs made payers other than patients responsible for medical care, nosology became a matter of great interest to those public and private payers. The most commonly used nosologies include International Classification of Diseases (ICD), the American Medical Association's Current Procedural Terminology, 4th Edition (CPT-4); the Health Care Financing Administration (HCFA, now known as the Centers for Medicare and Medicaid Services) Health Care Common Procedural Coding System (HCPCS); the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Revision (DSM-IV); Europe's Classification of Surgical Operations and Procedures, 4th Revision (OPCS-4); and the Agency for Healthcare Research and Quality's Clinical Classification Software (CCS). This paper focuses on the International Classification of Diseases, now in its ninth and soon to be tenth iteration; the most widely used classification of diseases. Beginning in 1900 with the ICD-1 version, this nosology has evolved from 179 to over 120,000 total codes in ICD-10-CM (ICD-10 2003; ICD-10-CM 2003). The use of codes has expanded from classifying morbidity and mortality information for statistical purposes to diverse sets of applications, including reimbursement, administration, epidemiology, and health services research. Since October 1 1983, when Medicare's Prospective Payment System (PPS) was enacted, diagnosis-related groups (DRGs) based on ICD codes emerged as the basis for hospital reimbursement for acute-care stays of Medicare beneficiaries (U.S. Congress 1985). Today the use of ICD coding for reimbursement is a vital part of health care operations. Health care facilities use ICD codes for workload and length-of-stay tracking as well as to assess quality of care. The Veterans Health Administration uses ICD codes to set capitation rates and allocate resources to medical centers caring for its 6 million beneficiaries. Medical research uses ICD codes for many purposes. By grouping patients according to their diagnoses, clinical epidemiologists use ICD codes to study patterns of disease, patterns of care, and outcomes of disease. Health services researchers use the codes to study risk-adjusted, cross-sectional, and temporal variations in access to care, quality of care, costs of care, and effectiveness of care. Medical and health services researchers commonly use ICD codes as inclusion and exclusion criteria to define sampling frames, to document the comorbidities of patients, report the incidence of complications, track utilization rates, and determine the case fatality and morbidity rates (see Calle et al. 2003 for a recent example) (Steinman, Landefeld, and Gonzales 2000; Calle et al. 2003; Charbonneau et al. 2003; Jackson et al. 2003; Martin et al. 2003; Studdert and Gresenz 2003). The widespread and diverse use of ICD codes demonstrates the central role nosology plays in health care. Increased attention to code accuracy has occurred both as a result of the application of ICD codes for purposes other than those for which the classifications were originally designed as well as because of the widespread use for making important funding, clinical, and research decisions. Code accuracy, defined as the extent to which the ICD nosologic code reflects the underlying patient's disease, directly impacts the quality of decisions that are based on codes, and therefore code accuracy is of great importance to code users. Accuracy is a complicated issue, however, as it influences each code application differently. Using the codes for reporting case fatality rates in persons hospitalized for influenza, for example, might require a different level of accuracy than using codes as the basis for reimbursing hospitals for providing expensive surgical services to insured persons. Therefore, users of disease classifications, just as users of any measure, must consider the accuracy of the classifications within their unique situations. An appreciation of the measurement context in which disease classifications take place will improve the accuracy of those classifications and will strengthen research and health care decisions based on those classifications. Researchers studying errors in the code assignment process have reported a wide range of errors. Studies in the 1970s found substantial errors in diagnostic and procedure coding. These error rates ranged from 20 to 80 percent (Institute of Medicine 1977; Corn 1981; Doremus and Michenzi 1983; Johnson and Appel 1984; Hsia et al. 1988). Studies in the 1980s reported slightly increased accuracy with average error rates around 20 percent, and most below 50 percent (Lloyd and Rissing 1985; Fischer et al. 1992; Jolis et al. 1993). Studies in the 1990s found rates similar to those of the 1980 studies, with error rates ranging from 0 to 70 percent (Benesch et al. 1997; Faciszewski, Broste, and Fardon 1997; Goldstein 1998). The inconsistency in the error rates and wide range of reported amounts of error is due largely to differences across study methods (i.e., different data sets, versions of the ICD classifications, conditions studied, number of digits compared, codes examined, etc.) (Bossuyt et al. 2004). However, variation in error rates is also influenced by the many different sources of errors that influence code accuracy (Green and Wintfeld 1993). By clearly specifying the code process and the types of errors and coding inconsistencies that occur in each study, researchers can begin to understand which errors are most common and most important in their situation. They can then institute steps for reducing those errors. If we think of the assignment of ICD codes as a common measurement process, then the person's true disease and the assigned ICD code represent true and observed variables, respectively. One approach to evaluating ICD code accuracy is to examine sources of errors that lead to the assignment of a diagnostic code that is not a fair representation of the patient's actual condition. Errors that differentiate the ICD code from the true disease include both random and systematic measurement errors. By understanding these sources of error, users can evaluate the limitations of the classifications and make better decisions based on them. In this manuscript, we (1) present the history of ICD code use, (2) summarize the general inpatient ICD coding process (from patient admission to the assignment of diagnostic codes), (3) identify potential sources of errors in the process, and (4) critique methods for assessing these errors.

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

Abstract: Background: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). Objectives: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD.

The cerebellum communicates with the basal ganglia.

Abstract: The cerebral cortex is interconnected with two major subcortical structures: the basal ganglia and the cerebellum. How and where cerebellar circuits interact with basal ganglia circuits has been a longstanding question. Using transneuronal transport of rabies virus in macaques, we found that a disynaptic pathway links an output stage of cerebellar processing, the dentate nucleus, with an input stage of basal ganglia processing, the striatum.

Integration of the Extranuclear and Nuclear Actions of Estrogen

Abstract: Estrogen receptors (ERs) are localized to many sites within the cell, potentially contributing to overall estrogen action. In the nucleus, estrogen mainly modulates gene transcription, and the resulting protein products determine the cell biological actions of the sex steroid. In addition, a small pool of ERs localize to the plasma membrane and signal mainly though coupling, directly or indirectly, to G proteins. In response to steroid, signal transduction modulates both nontranscriptional and transcriptional events and impacts both the rapid and more prolonged actions of estrogen. Cross-talk from membrane-localized ERs to nuclear ERs can be mediated through growth factor receptor tyrosine kinases, such as epidermal growth factor receptor and IGF-I receptor. Growth factor receptors enact signal transduction to kinases such as ERK and phosphatidylinositol 3-kinase that phosphorylate and activate nuclear ERs, and this can also occur in the absence of sex steroid. A complex relationship between the membrane and nuclear effects of estrogen also involves membrane-initiated phosphorylation of coactivators, recruiting these proteins to the nuclear transcriptosome. Finally, large pools of cytoplasmic ERs exist, and some are localized to mitochondria. The integration of sex steroid effects at distinct cellular locations of its receptor leads to important cellular physiological outcomes and are manifest in both reproductive and nonreproductive organs.

Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Abstract: background Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. methods Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. results Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 µ g per liter in 78 of 89 men (88 percent) and greater than 200 µ g per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 µ g per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. conclusions The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.

Cardiovascular Mortality Risk in Chronic Kidney Disease: Comparison of Traditional and Novel Risk Factors

Abstract: ContextElderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.ObjectiveTo compare traditional and novel risk factors as predictors of cardiovascular mortality.Design, Setting, and PatientsA total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.Main Outcome MeasuresCardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.ResultsAmong the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference = .15).ConclusionsTraditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.

Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study

Abstract: Background: Diabetes has been associated with an increased risk of hepatocellular carcinoma (HCC) in studies of referred patients. This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC. Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)-Medicare linked database to identify patients aged 65 years and older diagnosed with HCC and randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index date were examined. Inpatient and outpatient claims files were searched for diagnostic codes indicative of diabetes, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease, and haemochromatosis. HCC patients without these conditions were categorised as idiopathic. Unadjusted and adjusted odds ratios were calculated in logistic regression analyses. Results: We identified 2061 HCC patients and 6183 non-cancer controls. Compared with non-cancer controls, patients with HCC were male (66% v 36%) and non-White (34% v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis), diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjusted odds ratio for diabetes declined but remained significant (adjusted odds ratio 2.87 (95% confidence interval 2.49–3.30)). A significant positive interaction between HCV and diabetes was detected (p<0.0001). Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. Conclusions: Diabetes is associated with a 2–3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independent risk factor for HCC.

Amiodarone versus sotalol for atrial fibrillation.

Abstract: background The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. methods In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. results Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial f ibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. conclusions Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Transgenerational Effects of Posttraumatic Stress Disorder in Babies of Mothers Exposed to the World Trade Center Attacks during Pregnancy

Abstract: Context: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. Objective: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. Design: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. Results: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. Conclusions: The data suggest that effects of maternal PTSD related to cortisol ...

Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy

Abstract: Background: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). Objective: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. Design: A retrospective cohort identified through a city-wide prospective surveillance program. Methods: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. Results: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). Conclusions: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.

Nurse Moral Distress and Ethical Work Environment

Abstract: This study examined the relationship between moral distress intensity, moral distress frequency and the ethical work environment, and explored the relationship of demographic characteristics to moral distress intensity and frequency. A group of 106 nurses from two large medical centers reported moderate levels of moral distress intensity, low levels of moral distress frequency, and a moderately positive ethical work environment. Moral distress intensity and ethical work environment were correlated with moral distress frequency. Age was negatively correlated with moral distress intensity, whereas being African American was related to higher levels of moral distress intensity. The ethical work environment predicted moral distress intensity. These results reveal a difference between moral distress intensity and frequency and the importance of the environment to moral distress intensity.

Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity

Abstract: Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase-deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.