Evaluation of the Impact of Comorbidities on Omadacycline Pharmacokinetics.

Omadacycline is approved in the United States for the treatment of patients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections. Analyses were undertaken to evaluate pharmacokinetic differences among subjects or patients stratified by comorbidities. Differences in clearance by smoking status, history of diabetes mellitus, chronic lung disease, hypertension, heart failure, or coronary artery disease were evaluated using a Welch two-sample t test. Smoking was the only significant comorbidity after correction for sex, with a clinically insignificant difference of 13%. Omadacycline dose adjustments based on these comorbidities do not appear to be warranted.

Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study.

STUDY QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? SUMMARY ANSWER: PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). WHAT IS KNOWN ALREADY: Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. STUDY DESIGN, SIZE, DURATION: This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12 631 FET cycles in 10 060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. MAIN RESULTS AND THE ROLE OF CHANCE: In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age <35 years, 1.45 (95% CI: 1.21, 1.75) for ages 35-37 years, 1.89 (95% CI: 1.56, 2.29) for ages 38-40, 2.62 (95% CI: 1.94-3.53) for ages 41-42, and 3.80 (95% CI: 2.52, 5.72) for ages >42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age <35 years, 1.37 (95% CI: 1.14, 1.64) for ages 35-37 years, 1.68 (95% CI: 1.40, 2.03) for ages 38-40 years, 2.19 (95% CI: 1.65, 2.90) for ages 41-42, and 2.31 (95% CI: 1.60, 3.32) for ages >42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age <35 years, 0.85 (95% CI: 0.65, 1.11) for ages 35-37 years, 0.81 (95% CI: 0.60, 1.08) for ages 38-40, 0.86 (95% CI: 0.58, 1.27) for ages 41-42, and 0.58 (95% CI: 0.32, 1.07) for ages >42 years. LIMITATIONS, REASONS FOR CAUTION: The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. STUDY FUNDING/COMPETING INTEREST(S): There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Fetal echocardiographic assessment of cardiovascular impact of prolonged support on EXTrauterine Environment for Neonatal Development (EXTEND) system.

OBJECTIVE: EXTrauterine Environment for Neonatal Development (EXTEND) is a system to support ongoing fetal growth and organ development in an extrauterine environment, utilizing a pumpless low-resistance oxygenator circuit. The aim of this study was to evaluate hemodynamics and cardiac function in fetal sheep sustained on the EXTEND system. METHODS: This was a prospective study of fetal sheep supported for a minimum of 3 weeks on EXTEND. Hemodynamic parameters were assessed weekly and included heart rate, mean arterial pressure (MAP), Doppler-echocardiography-derived cardiac output (CO), pulsatility indices (PIs) of the fetal middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus and cardiac function, as assessed by speckle-tracking-derived global longitudinal strain and strain rate in the right (RV) and left (LV) ventricles. Parameters were compared at 0 days and 1, 2 and 3 weeks following placement on EXTEND. RESULTS: Of 10 fetal sheep enrolled, seven survived for 3 weeks and were included in the analysis. Median gestational age at cannulation was 107 (range, 95-109) days. Heart rate decreased and MAP increased significantly, but within acceptable ranges, during the study period. The quantities and relative ratios of right and left CO remained stable within the anticipated physiological range throughout the study period. Vascular tracings and PIs appeared to be similar to those seen normally in the natural in-utero state, with MCA-PI being higher than UA-PI. UA tracings demonstrated maintained abundant diastolic flow despite the absence of placental circulation. In both the RV and LV, strain decreased significantly at 1 and 2 weeks relative to baseline but returned to baseline values by week 3. CONCLUSIONS: The EXTEND mechanical support system replicates natural physiology and creates a stable and sustainable cardiovascular construct that supports growth over a 3-week period. However, there is a period of depressed contractility within the first week with subsequent improvement by week 3. This may reflect a period of physiological accommodation that warrants further investigation. This study lays the foundation for further exploration as the EXTEND system moves towards human application. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The effect of operating lights on laminar flow: an experimental study using neutrally buoyant helium bubbles.

AIMS: The interaction between surgical lighting and laminar airflow is poorly understood. We undertook an experiment to identify any effect contemporary surgical lights have on laminar flow and recommend practical strategies to limit any negative effects. MATERIALS AND METHODS: Neutrally buoyant bubbles were introduced into the surgical field of a simulated setup for a routine total knee arthroplasty in a laminar flow theatre. Patterns of airflow were observed and the number of bubbles remaining above the surgical field over time identified. Five different lighting configurations were assessed. Data were analysed using simple linear regression after logarithmic transformation. RESULTS: In the absence of surgical lights, laminar airflow was observed, bubbles were cleared rapidly and did not accumulate. If lights were placed above the surgical field laminar airflow was abolished and bubbles rose from the surgical field to the lights then circulated back to the surgical field. The value of the decay parameter (slope) of the two setups differed significantly; no light (b = -1.589) versus one light (b = -0.1273, p < 0.001). Two lights touching (b = -0.1191) above the surgical field had a similar effect to that of a single light (p = 0. 2719). Two lights positioned by arms outstretched had a similar effect (b = -0.1204) to two lights touching (p = 0.998) and one light (p = 0.444). When lights were separated widely (160 cm), laminar airflow was observed but the rate of clearance of the bubbles remained slower (b = -1.1165) than with no lights present (p = 0.004). CONCLUSION: Surgical lights have a significantly negative effect on laminar airflow. Lights should be positioned as far away as practicable from the surgical field to limit this effect. Cite this article: Bone Joint J 2017;99-B:1061-6.

Surgical excision of ununited hook of hamate fractures via the carpal tunnel approach.

INTRODUCTION: Direct excision of a symptomatic ununited hook of hamate fracture is the gold standard, most frequently via a Guyon space approach. The open carpal tunnel approach is another option, which has not previously been commonly considered and not reported in a peer review journal. Our study aims to highlight the carpal tunnel approach as a successful technique in a consecutive series of ununited hook of hamate fractures. PATIENTS AND METHODS: Seven patients (all male and mean age 30.7 years) were reviewed with symptomatic ununited fractures following a period of cast immobilization. All the patients operated on underwent excision of the hook of hamate fragment via the open carpal tunnel approach. RESULTS: All patients successfully returned to their pre-injury level of functioning after 8-12 weeks and there were no complications. CONCLUSIONS: Our study highlights the open carpal tunnel approach as a successful technique for open excision of symptomatic ununited hook of hamate fractures, because of its familiarity, ease of performance, excellent visualization and low morbidity. Level of Evidence IV Case Series.

The influence of surgical hoods and togas on airborne particle concentration at the surgical site: an experimental study.

BACKGROUND: Arthroplasty surgeons are increasingly using personal protection systems with helmets. It is theoretically possible for the fans in these helmets to blow squames, sweat droplets and orobronchial fomites onto the surgical site. A controlled experiment was set up to investigate the effect of different surgical gowns on counts of airborne particles measuring ≥0.3 µm, using a hand-held particle counter. METHODS: The clothing that was sequentially tested included the following: 1. Barrier(®) surgical gown (single use) made from nonwoven polypropylene (Mölnlycke Health Care Ltd, Dunstable, UK) 2. Stryker(®) T5 Helmet (reusable) covered with a disposable Stryker(®) T4/T5 urethane hood worn separate to and enclosed by the Barrier(®) surgical gown both at the front and back 3. Stryker(®) T5 Helmet (reusable) worn within a disposable Stryker(®) T4/T5 urethane zippered toga (Stryker Corporation, Kalamazoo, MI, USA) Six readings were taken for each of the following three setups in a randomised order: 1. Gown: surgeon with surgical gown and face mask 2. Hood: surgeon with surgical gown and hood, maximum fan speed 3. Toga: surgeon with toga, maximum fan speed Wilcoxon rank sum tests were applied to assess equality of means between the three occlusive measures (gown, hood, toga). P values were computed based upon one-sided tests and adjusted for multiple comparisons using the Bonferroni correction. RESULTS: The mean particle counts (over more than 5 L of air) for the three set-ups were: gown: 1178 (least protective), hood: 328, toga: 42 (most protective). There was a significant reduction in particle counts for the toga versus gown (p = 0.007) and toga versus hood (p = 0.037); differences in particle counts were not significant between the hood and gown (p = 0.140). CONCLUSIONS: The fans in the helmets do not increase contaminants by blowing particles from the head area. A significant reduction in surgeon-originated contaminants was seen with the toga compared to both the hood/gown separate ensemble and gowns alone.

Bilateral DCIS following gynecomastia surgery. Role of nipple sparing mastectomy. A case report and review of literature.

Bilateral ductal carcinoma in situ of breast is a very rare disease in men. Ductal carcinoma in situ (DCIS) is an abnormal proliferation that involves the ductal epithelium and it has the potential of evolving into an invasive tumour. Gynaecomastia (female like breast in men) is a benign condition though it is associated with a reported 3% incidence of unilateral invasive breast cancer.(2) Synchronous bilateral breast cancer in association with gynaecomastia is exceptionally rare. The recommended treatment for DCIS in male is mastectomy. So far only 2 cases of bilateral DCIS in male patients has been reported in the literature treated with skin and nipple sparing mastectomies. We report another case of synchronous bilateral DCIS in a male treated with skin and nipple sparing mastectomies. A 44 year-old man with history of long-standing gynecomastia. He had no identifiable risk factor for the development of cancer. His pre operative assessment of breast including mammograms was normal. He underwent bilateral subcutaneous mastectomies, with subsequent incidental diagnosis of synchronous bilateral ductal carcinoma in situ. The case was discussed in multidisciplinary team meeting and the need for further surgery was felt including excision of nipple areola complex. However considering patient wishes, cosmetic outcome and recent literature it was decided to preserve nipple areola complex (NAC) with regular follow up evaluation. Our patient at completion of 18 months of treatment is doing well with no signs of local recurrence.

Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics.

We investigated the capacity of patient warming devices to disrupt the ultra-clean airflow system. We compared the effects of two patient warming technologies, forced-air and conductive fabric, on operating theatre ventilation during simulated hip replacement and lumbar spinal procedures using a mannequin as a patient. Infection data were reviewed to determine whether joint infection rates were associated with the type of patient warming device that was used. Neutral-buoyancy detergent bubbles were released adjacent to the mannequin's head and at floor level to assess the movement of non-sterile air into the clean airflow over the surgical site. During simulated hip replacement, bubble counts over the surgical site were greater for forced-air than for conductive fabric warming when the anaesthesia/surgery drape was laid down (p = 0.010) and at half-height (p < 0.001). For lumbar surgery, forced-air warming generated convection currents that mobilised floor air into the surgical site area. Conductive fabric warming had no such effect. A significant increase in deep joint infection, as demonstrated by an elevated infection odds ratio (3.8, p = 0.024), was identified during a period when forced-air warming was used compared to a period when conductive fabric warming was used. Air-free warming is, therefore, recommended over forced-air warming for orthopaedic procedures.

Anticancer activity of botanical compounds in ancient fermented beverages (review).

Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.

Multiple origins of cultivated grapevine (Vitis vinifera L. ssp. sativa) based on chloroplast DNA polymorphisms.

The domestication of the Eurasian grape (Vitis vinifera ssp. sativa) from its wild ancestor (Vitis vinifera ssp. sylvestris) has long been claimed to have occurred in Transcaucasia where its greatest genetic diversity is found and where very early archaeological evidence, including grape pips and artefacts of a 'wine culture', have been excavated. Whether from Transcaucasia or the nearby Taurus or Zagros Mountains, it is hypothesized that this wine culture spread southwards and eventually westwards around the Mediterranean basin, together with the transplantation of cultivated grape cuttings. However, the existence of morphological differentiation between cultivars from eastern and western ends of the modern distribution of the Eurasian grape suggests the existence of different genetic contribution from local sylvestris populations or multilocal selection and domestication of sylvestris genotypes. To tackle this issue, we analysed chlorotype variation and distribution in 1201 samples of sylvestris and sativa genotypes from the whole area of the species' distribution and studied their genetic relationships. The results suggest the existence of at least two important origins for the cultivated germplasm, one in the Near East and another in the western Mediterranean region, the latter of which gave rise to many of the current Western European cultivars. Indeed, over 70% of the Iberian Peninsula cultivars display chlorotypes that are only compatible with their having derived from western sylvestris populations.

Relation between policies and work related assault: Minnesota Nurses' Study.

AIMS: To assess the relation between violence prevention policies and work related assault. METHODS: From Phase 1 of the Minnesota Nurses' Study, a population based survey of 6300 Minnesota nurses (response 79%), 13.2% reported experiencing work related physical assault in the past year. In Phase 2, a case-control study, 1900 nurses (response 75%) were questioned about exposures relevant to violence, including eight work related violence prevention policy items. A comprehensive causal model served as a basis for survey design, analyses, and interpretation. Sensitivity analyses were conducted for potential exposure misclassification and the presence of an unmeasured confounder. RESULTS: Results of multiple regression analyses, controlling for appropriate factors, indicated that the odds of physical assault decreased for having a zero tolerance policy (OR = 0.5, 95% CI 0.4 to 0.8) and having policies regarding types of prohibited violent behaviours (OR = 0.5, 95% CI 0.3 to 0.9). Analyses adjusted for non-response and non-selection resulted in wider confidence intervals, but no substantial change in effect estimates. CONCLUSIONS: It appears that some work related violence policies may be protective for the population of Minnesota nurses.

Risk factors for work related violence in a health care organization.

OBJECTIVE: Identify the exposure effects of job family, patient contact, and supervisor support on physical and non-physical work related violence. DESIGN: Cross sectional study of employees in a Midwest health care organization, utilizing a specially designed mailed questionnaire and employer secondary data. SUBJECTS: Respondents included 1751 current and former employees (42% response rate). RESULTS: Physical and non-physical violence was experienced by 127 (7.2%) and 536 (30.6%) of the respondents, respectively. Multivariate analyses of physical violence identified increased odds for patient care assistants (odds ratio (OR) 2.5, 95% confidence interval (CI) 1. 1 to 6.1) and decreased odds for clerical workers (OR 0.1, 95% CI 0.03 to 0.5). Adjusted for job family, increased odds of physical violence were identified for moderate (OR 5.9, 95% CI 2.1 to 16.0) and high (OR 7.8, 95% CI 2.9 to 20.8) patient contact. Similar trends were identified for non-physical violence (OR 1.4, 95% CI 1.1 to 2.0 and OR 1.7, 95% CI 1.3 to 2.3). Increased supervisor support decreased the odds of both physical (OR 0.7, 95% CI 0.6 to 0.95) and non-physical violence (OR 0.5, 95% CI 0.4 to 0.6), adjusting for job family and demographic characteristics. CONCLUSIONS: Increased odds of physical violence were identified for the job family of nurses, even when adjusted for patient contact. Increased patient contact resulted in increased physical and non-physical violence, independent of job family, while supervisor support resulted in decreased odds of physical and non-physical violence.

An epidemiological study of the magnitude and consequences of work related violence: the Minnesota Nurses' Study.

AIMS: To identify the magnitude of and potential risk factors for violence within a major occupational population. METHODS: Comprehensive surveys were sent to 6300 Minnesota licensed registered (RNs) and practical (LPNs) nurses to collect data on physical and non-physical violence for the prior 12 months. Re-weighting enabled adjustment for potential biases associated with non-response, accounting for unknown eligibility. RESULTS: From the 78% responding, combined with non-response rate information, respective adjusted rates per 100 persons per year (95% CI) for physical and non-physical violence were 13.2 (12.2 to 14.3) and 38.8 (37.4 to 40.4); assault rates were increased, respectively, for LPNs versus RNs (16.4 and 12.0) and males versus females (19.4 and 12.9). Perpetrators of physical and non-physical events were patients/clients (97% and 67%, respectively). Consequences appeared greater for non-physical than physical violence. Multivariate modelling identified increased rates for both physical and non-physical violence for working: in a nursing home/long term care facility; in intensive care, psychiatric/behavioural or emergency departments; and with geriatric patients. CONCLUSIONS: Results show that non-fatal physical assault and non-physical forms of violence, and relevant consequences, are frequent among both RNs and LPNs; such violence is mostly perpetrated by patients or clients; and certain environmental factors appear to affect the risk of violence. This serves as the basis for further analytical studies that can enable the development of appropriate prevention and control efforts.

Characteristics and outcomes among patients undergoing coronary artery bypass grafting in western Sweden and Minneapolis-St Paul, Minnesota.

BACKGROUND: The purpose of this study was to compare patient selection, operative factors, and survival for coronary artery bypass grafting (CABG) for coronary heart disease in Minneapolis-St Paul (MSP), Minnesota, and Western Sweden (WS). METHODS AND RESULTS: All patients from WS between 1988 and 1991 (n = 2365) and a 17% random sample of MSP patients between 1985 and 1990 (n = 1659) who underwent CABG surgery were studied. CABG was 3 times greater in MSP. MSP patients had significantly more obesity, cigarette smoking, prior CABG, and prior coronary angioplasty. WS patients had more and longer angina pectoris, better left ventricular function, and waited longer from previous acute MI until CABG. WS patients had more internal mammary artery graphs and a shorter aortic cross-clamp time. At discharge, WS patients received more beta-blockers and antiplatelet agents, whereas MSP patients received more calcium channel blockers and digitalis. Age-adjusted mortality rate at 28 days was significantly higher in MSP but not at 3 years. Adjustment for patient characteristics and treatment factors reduced or eliminated these differences. CONCLUSIONS: Although coronary heart disease rates were higher in WS, age-adjusted CABG rates were 3-fold higher in MSP. Better survival among WS patients was associated with differences in patient selection and clinical and treatment characteristics because MSP patients were more severely ill and at increased risk. Health system characteristics and practice may account for these differences.

Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression.

Lipopolysaccharide (LPS) induces human monocytes to express many proinflammatory mediators, including the procoagulant molecule tissue factor (TF) and the cytokine tumor necrosis factor alpha (TNF-alpha). The TF and TNF-alpha genes are regulated by various transcription factors, including nuclear factor (NF)-kappaB/Rel proteins and Egr-1. In this study, the role of the MEK-ERK1/2 mitogen-activated protein kinase (MAPK) pathway in LPS induction of TF and TNF-alpha gene expression in human monocytic cells was investigated. The MAPK kinase (MEK)1 inhibitor PD98059 reduced LPS induction of TF and TNF-alpha expression in a dose-dependent manner. PD98059 did not affect LPS-induced nuclear translocation of NF-kappaB/Rel proteins and minimally affected LPS induction of kappaB-dependent transcription. In contrast, PD98059 and dominant-negative mutants of the Ras-Raf1-MEK-ERK (extacellular signal-regulated kinase) pathway strongly inhibited LPS induction of Egr-1 expression. In kinetic experiments LPS induction of Egr-1 expression preceded induction of TF expression. In addition, mutation of the Egr-1 sites in the TF and TNF-alpha promoters reduced expression of these proinflammatory genes. It was demonstrated that LPS induction of the Egr-1 promoter was mediated by 3 SRE sites, which bound an LPS-inducible complex containing serum response factor and Elk-1. LPS stimulation transiently induced phosphorylation of Elk-1 and increased the functional activity of a GAL4-Elk-1TA chimeric protein via the MEK-ERK1/2 pathway. The data indicate that LPS induction of Egr-1 gene expression is required for maximal induction of the TNF-alpha and TF genes in human monocytic cells.

Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey.

BACKGROUND: Coronary heart disease (CHD) mortality continued to decline from 1985 to 1997. METHODS AND RESULTS: We tabulated CHD deaths (ICD-9 codes 410 through 414) in the Minneapolis/St Paul, Minnesota, area. For 1985, 1990, and 1995, trained nurses abstracted the hospital records of patients 30 to 74 years old with a discharge diagnosis of acute CHD (ICD-9 codes 410 or 411). Acute myocardial infarction (AMI) events were validated and followed for 3-year all-cause mortality. Between 1985 and 1997, age-adjusted CHD mortality rates in Minneapolis/St Paul fell 47% and 51% in men and women, respectively; the comparable declines in US whites were 34% and 29%. In-hospital mortality declined faster than out-of-hospital mortality. The rate of AMI (ICD-9 code 410) hospital discharges declined almost 20% between 1985 and 1995, whereas the discharge rate for unstable angina (ICD-9 code 411) increased substantially. The incidence of hospitalized definite AMI declined approximately 10%, whereas recurrence rates fell 20% to 30%. Three-year case fatality rates after hospitalized AMI decreased consistently by 31% and 41% in men and women, respectively. In-hospital administration of thrombolytic therapy, emergency angioplasty, ACE inhibitors, beta-blockers, heparin, and aspirin increased greatly. CONCLUSIONS: Declining out-of-hospital death rates, declining incidence and recurrence of AMI in the population, and marked improvements in the survival of AMI patients all contributed to the 1985 to 1997 decline of CHD mortality in the Minneapolis/St Paul metropolitan area. The effects of early and late medical care seem to have had the greatest contribution to rates during this time period.

Short-term variability in the measurement of plasma homocysteine, fasting and post-methionine loading.

OBJECTIVES: Hyperhomocysteinemia is associated with premature cerebral, peripheral and coronary vascular disease. Evaluation of the significance of changes in plasma total homocysteine (tHcy) results obtained by analysis of serial specimens may be accomplished only by taking into account biologic (between-person and within-person) as well as analytical variation. Since the repeatability of a measurement significantly determines our ability to associate tHcy level with the presence of disease, this study was performed to evaluate various components of variation in tHcy values. DESIGN AND METHODS: We report the within-person, between-person, and methodological variability of tHcy, both fasting and postmethionine load (PML) values, in 20 healthy volunteers from whom samples were drawn weekly for 4 weeks. RESULTS: The short-term reliability coefficient (R) was 0.72 for fasting tHcy and 0.83 for PML tHcy. CONCLUSIONS: The current study demonstrates for the first time that the short-term reliability coefficient for PML tHcy is relatively high (0.83), suggesting that an individual's PML tHcy, like fasting tHcy, is relatively constant over at least one month, and that a single measurement should provide a reasonable characterization of an individual's PML tHcy concentration.

Cardiovascular risk factors and cognitive decline in middle-aged adults.

OBJECTIVE: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. METHODS: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. RESULTS: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. CONCLUSIONS: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.