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Combined transluminal angioplasty and infrainguinal reconstruction in multilevel atherosclerotic disease.

Patients with multilevel atherosclerotic disease represent a difficult surgical challenge. This report is a retrospective review of 46 patients who were treated using a combination of iliac transluminal angioplasty and infrainguinal reconstruction. There were 42 male and 4 female patients with an average age of 62 years (range: 40 to 74 years). Follow-up ranged from 1 month to 10 years (mean: 27.3 months). These patients had multiple health problems typical of patients with peripheral vascular disease, including coronary artery disease (67%), hypertension (61%), and diabetes mellitus (42%); 80% of the patients were smokers. Forty-one patients were treated for rest pain and/or tissue loss, while five were treated for incapacitating claudication. Forty-three patients had a combination of angioplasty and distal bypass, while 3 patients had a form of femoral endarterectomy. Iliac artery pressure gradients were reduced from 35.4 +/- 4 mm Hg preangioplasty to 0.6 +/- 0.3 mm Hg postangioplasty. The procedures were well tolerated with no mortality and four serious complications. Vascular laboratory studies showed an improvement in the mean ankle-brachial index from 0.35 +/- 0.03 preoperatively to 0.71 +/- 0.04 postoperatively (p less than 0.05). Life-table analysis revealed a 72% 5-year primary patency rate, with a 93% 5-year limb salvage. Eight patients required a secondary procedure to maintain limb salvage. Five patients underwent amputation, three due to early graft thrombosis and two due to late graft failure. We conclude that combined iliac angioplasty and infrainguinal reconstruction is a safe and effective method for managing the patient with severe multilevel atherosclerotic disease.

Adult↗

Risking risk: the influence of types of capital and social networks on the injection practices of drug users.

Although syringe exchange and other harm reduction interventions have generally been effective in reducing bloodborne pathogen incidence among injection drug users (IDUs), in some cases a minority of IDUs continues to engage in risky injection behavior. Building on emerging perspectives in social epidemiology and research on drug use in anthropology that point to the importance of examining fundamental social causes of risk behavior, or what puts individuals at risk for risk, this study used a multilevel perspective to explore whether forms of capital, social network characteristics, and other contextual factors influence continued risky injection behavior. Quantitative and qualitative data were collected on IDUs in the city of Marseilles, France, where sterile injection equipment has been legal and officially promoted since 1995. In multivariate analysis on data concerning active users, location in the densest part of a large, interconnected network of IDUs greatly increased the likelihood of risky injection practices, while there was a non-significant tendency for low Acquired Cultural and Economic Capital to predict this behavior. Among the strongest individual-level characteristics to predict this outcome were illicit use of prescribed medication, generally high dose buprenorphine, and unprotected sex. Parental abuse of psychoactive drugs during the subject's childhood, on the other hand, greatly decreased the chances of engaging in risky injection behavior. Additionally, qualitative data analysis suggests that risky injection may be linked to lack of resources to procure drugs, and not simply to inadequate sterile injection equipment. Further research, including ecological models, is needed to better understand how fundamental social conditions are related to "risk for risk". However, public health interventions can already address the need for community-level interventions, while rethinking the consequences of inaccessible drugs and unintended "leakage" from the introduction of buprenorphine and other medicalized treatments for opiate dependency.

Adult↗

Modelling health-related performance indices.

PRIMARY OBJECTIVE: The purpose of the present review is to critically examine the various models used to describe health-related performance indices (e.g. grip-strength, lung function, arterial blood pressure, anaerobic and aerobic power, etc.). MAIN OUTCOMES AND RESULTS: The majority of health-related performance indices are known to increase proportionally with body size and decline with age, although some, for example arterial blood pressure and cholesterol, increase with both age and excessive body weight. Historically, the confounding effects of body size and age have been controlled using multiple linear or polynomial regression models assuming a constant additive error variance. Based on maximum likelihood goodness-of-fit criterion, an alternative class of allometric models with a multiplicative error term arc shown to describe such proportional relationships more adequately in both cross-sectional and longitudinal studies. CONCLUSIONS: When modelling health-related performance indices, multiplicative, allometric models incorporate the concept of a proportional association as an integral part of its model form. Such models guarantee realistic values of health-related response variables both within and beyond the range of observations, ensuring biologically sound estimates of the response variables for subjects of all ages. After a logarithmic transformation, the models can be fitted using ordinary linear regression that will naturally help to overcome the heteroscedasticity observed in such data. However, if the logarithmic transformation fails to provide a constant error variance, an alternative approach is to model the error variance itself using log-linear regression. For longitudinal data, the use of multilevel modelling provides an alternative method of modelling error variation observed in health-related performance indices.

Adolescent↗

Principles of multilevel modelling.

BACKGROUND: Multilevel modelling, also known as hierarchical regression, generalizes ordinary regression modelling to distinguish multiple levels of information in a model. Use of multiple levels gives rise to an enormous range of statistical benefits. To aid in understanding these benefits, this article provides an elementary introduction to the conceptual basis for multilevel modelling, beginning with classical frequentist, Bayes, and empirical-Bayes techniques as special cases. The article focuses on the role of multilevel averaging ('shrinkage') in the reduction of estimation error, and the role of prior information in finding good averages.

Abortion, Spontaneous↗

Ecologic versus individual-level sources of bias in ecologic estimates of contextual health effects.

A number of authors have attempted to defend ecologic (aggregate) studies by claiming that the goal of those studies is estimation of ecologic (contextual or group-level) effects rather than individual-level effects. Critics of these attempts point out that ecologic effect estimates are inevitably used as estimates of individual effects, despite disclaimers. A more subtle problem is that ecologic variation in the distribution of individual effects can bias ecologic estimates of contextual effects. The conditions leading to this bias are plausible and perhaps even common in studies of ecosocial factors and health outcomes because social context is not randomized across typical analysis units (administrative regions). By definition, ecologic data contain only marginal observations on the joint distribution of individually defined confounders and outcomes, and so identify neither contextual nor individual-level effects. While ecologic studies can still be useful given appropriate caveats, their problems are better addressed by multilevel study designs, which obtain and use individual as well as group-level data. Nonetheless, such studies often share certain special problems with ecologic studies, including problems due to inappropriate aggregation and problems due to temporal changes in covariate distributions.

Bias↗

Can school income and racial/ethnic composition explain the racial/ethnic disparity in adolescent physical activity participation?

OBJECTIVE: Our goal was to determine if racial/ethnic disparities in adolescent boys' and girls' physical activity participation exist and persist once the school attended is considered. METHODS: We performed a cross-sectional analysis of 17,007 teens in the National Longitudinal Study of Adolescent Health. Using multivariate linear regression, we examined the association between adolescent self-reported physical activity and individual race/ethnicity stratified by gender, controlling for a wide range of sociodemographic, attitudinal, behavioral, and health factors. We used multilevel analyses to determine if the relationship between race/ethnicity and physical activity varied by the school attended. RESULTS: Participants attended racially segregated schools; approximately 80% of Hispanic and black adolescent boys and girls attended schools with student populations that were <66% white, whereas nearly 40% of the white adolescents attended schools that were >94% white. Black and Hispanic adolescent girls reported lower levels of physical activity than white adolescent girls. There were more similar levels of physical activity reported in adolescent boys, with black boys reporting slightly more activities. Although black and Hispanic adolescent girls were more likely to attend poorer schools with overall lower levels of physical activity in girls; there was no difference within schools between black, white, and Hispanic adolescent girls' physical activity levels. Within the same schools, both black and Hispanic adolescent boys had higher rates of physical activity when compared with white adolescent boys. CONCLUSIONS: In this nationally representative sample, lower physical activity levels in Hispanic and black adolescent girls were largely attributable to the schools they attended. In contrast, black and Hispanic males had higher activity levels than white males when attending the same schools. Future research is needed to determine the mechanisms through which school environments contribute to racial/ethnic disparities in adolescent physical activity and will need to consider gender differences in these racial/ethnic disparities.

Adolescent↗

Characterization of mycobacteria species by HPLC and pattern recognition.

Multivariate methods of analysis are used to characterize 36 mycobacteria species following high-performance liquid chromatography (HPLC) of extracts of mycolic acids. After growth of the bacterial cultures, cell wall mycolic acids are saponified, extracted, then derivatized to the p-bromophenacyl esters. Reversed-phase HPLC with gradient elution separates 38 peaks in 10 min, plus an internal standard. A training set of 276 samples is composed and classification models are developed to predict the mycobacteria species. Classifications during the training phase are 91 and 95% accurate for single-pass and multilevel approaches, respectively. Validation is performed with a 549-sample set; successful classifications of known species are 87 and 92%, respectively. Bunching the predictions of MAIS complex species into one category improves the latter result to 97% correctly classified species. Fourteen of the 27 species (including M. tuberculosis) are classified without error in the validation data set.

Bacterial Typing Techniques↗

The role of individual and contextual socioeconomic circumstances on mortality: analysis of time variations in a city of north west Italy.

STUDY OBJECTIVE: To evaluate the independent and mutual effects of neighbourhood deprivation and of individual socioeconomic conditions on mortality and to assess the trends over the past 30 years and the residual neighbourhood heterogeneity. DESIGN: General and cause specific mortality was analysed as a function of time period, highest educational level achieved, housing conditions, and neighbourhood deprivation, using multilevel Poisson models stratified by gender and age class. SETTING: The study was conducted in Turin, a city in north west Italy with nearly one million inhabitants and consisting of 23 neighbourhoods. PARTICIPANTS: The study population included three cohorts of persons aged 15 years or older, recorded in the censuses of 1971, 1981, and 1991 and followed up for 10 years after each census. MAIN RESULTS: Individual and contextual socioeconomic conditions showed an independent and significant impact on mortality, both among men and women, with significantly higher risks for coronary heart and respiratory diseases among people, aged less than 65 years, residing in deprived neighbourhoods (9% and 15% excess for coronary heart diseases, 20% and 24% for respiratory diseases, respectively for men and women living in deprived neighbourhoods compared with rich). The decreasing time trend in general mortality was less pronounced among men with lower education and poorer housing conditions, compared with their more advantaged counterparts; the same was found in less educated women aged less than 65 years. CONCLUSIONS: These results and further developments in the evaluation of impact and mechanisms of other contextual effects can provide information for both health and non-health oriented urban policies.

Adolescent↗

Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies.

The aim of this study was to encapsulate glutathione (GSH) alone or in combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in Eudragit RS 100 microparticles (MPs), and to evaluate these novel delivery systems for oral administration of the considered tripeptide. The MPs were prepared by an O/O emulsion-solvent evaporation method according to a multilevel experimental design involving the volume of liquid paraffin, the HP-beta-CD amount, and the drug/polymer ratio as independent variables. The effects of these parameters on particle size, entrapment efficiency, and drug release were investigated. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GSH and Eudragit RS 100 polymer and to characterize the physical state of drug within the MPs. The release profiles of GSH from MPs were examined in vitro at pH 1.2, 6.8. and 7.4 using the USP III (BioDis) dissolution apparatus. In general, a slow and zero-order release of GSH from MPs at pH 1.2 occurred, while at higher pH values considerable amounts of glutathione disulfide (i.e., GSSG) were observed. The enzymatic stability and the intestinal permeability of some GSH-containing MPs were assessed by using pepsin, alpha-chymotrypsin, gamma-glutamyl-transpeptidase and everted frog intestinal sac methodology, respectively. The results suggest that GSH-loaded Eudragit RS 100 MPs containing HP-beta-CD represent a new sustained GSH delivery system useful for the oral administration of the examined tripeptide.

2-Hydroxypropyl-beta-cyclodextrin↗

A cross-level units-of-analysis approach to individual differences in skill acquisition.

A recent multiple-stage model posits that the individual-difference factors influencing performance vary depending on skill acquisition stage (P. L. Ackerman, 1989, 1990). In the current study, the authors examine the effect of ability in early skill acquisition and extend earlier research by examining the roles of self-efficacy and task familiarity. Furthermore, learning-curve modeling with multilevel models is used to alleviate prior analytical problems. Subjects (N = 115) performed an air traffic control simulation task. Nonlinear learning-curve parameters were estimated for each subject using a negative exponential model (see D. R. Rogosa & J. B. Willett, 1985). Cognitive ability, self-efficacy, and task familiarity were then used to predict learning-curve parameters: learning-rate constant and asymptotic performance. Results revealed that ability, self-efficacy, and familiarity predicted the learning-rate constant, whereas self-efficacy predicted asymptotic performance.

Adult↗

Phospholipid hydroperoxide glutathione peroxidase.

In acute inflammation the activated leukocytes generate cytotoxic oxygen free radicals. The role of these radical species in the cellular damage following an acute inflammatory reaction is well known. On the other hand the extent of the cellular damage must be dependent on both the rate of the free-radical generation and the scavenging capacity of the tissues. Among the enzymes acting in the inhibition of this damage, a key role seems to be played by the new selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Indeed the reduction of membrane hydroperoxides constitutes a secondary line of defence against lipid peroxidation, preventing the decomposition of hydroperoxides leading to the formation of new radicals. This enzyme inhibits lipid peroxidation and is as active as glutathione peroxidase on phospholipid hydroperoxides, on which no previously known peroxidase is active. Its protective activity for biomembranes, and the kinetic analysis in the presence of detergents, suggest its interfacial character. The inhibition of lipid peroxidation in the membranes apparently requires this enzyme, along with glutathione and vitamin E, in order to reduce the rate of the initiation reactions. This synergism bears out the role of this enzyme in the multilevel defence system against free-radical damage in tissues.

Animals↗

Multilevel growth curve models with covariate effects: application to recovery after stroke.

In measuring the progression of, or recovery from, a disease an individual's outcome may be assessed on a number of occasions. A model of the relationship between outcome and time since disease occurred which accounts for patient characteristics could be used to describe patterns of recovery, to predict outcome for a patient, or to evaluate health interventions. We use multilevel models to analyse such data, focusing on the choice of powers of time both for mean outcome and covariate effects. We give equations for predicted outcome and corresponding standard errors (i) based only on baseline characteristics, and (ii) by conditioning on previous outcomes for an individual. In a study of 331 stroke patients, outcome was measured approximately 0, 2,4,6 and 12 months after stroke. Patient characteristics included age, sex, and pre-stroke handicap, together with stroke-severity indicators (presence of limb deficit, dysphasia, dysarthria or incontinence). Of these, only the effects of age, dysphasia and presence of deficit varied with time. Conditioning on previous observations improved the accuracy of predictions. The outcome variable clearly had a skewed distribution, and the model residuals showed evidence of non-Normality. We discuss alternative models for non-Normal data, and show that, here, the standard (Normal errors) multilevel model gives equivalent parameter estimates and predictions to those obtained from alternative models.

Aged↗

Emerging measurement and statistical methods in physical activity research.

Although many studies have attempted to identify mediators and moderators of changes in physical activity involvement, the literature is inconclusive regarding which variable(s) relate to physical activity behavior change. The Cooper 2001 Conference series dedicated a session to discussing measurement and statistical methods that could contribute to advancing this research agenda. This article focuses on four such methodologic approaches: qualitative; psychometric; latent-variable, structural equation modeling; and multilevel modeling. The article presents a brief overview of these methods and discusses potential advantages and limitations of using them.

Factor Analysis, Statistical↗

Challenges in monitoring the natural attenuation of spatially variable plumes.

Monitored natural attenuation may be applied as a risk-based remediation strategy if it can be established that contaminants are or will be reduced to some acceptable level at or before a compliance point. Contaminant attenuation is often attributed to intrinsic biodegradation, which in some circumstances may occur only at the plume fringes where electron acceptors from the surrounding uncontaminated zones mix by dispersion and diffusion with the plume. However, due to the common spatial and temporal variability exhibited by many plumes, the centreline monitoring approaches advocated in many natural attenuation protocols may be unable to detect natural attenuation occurring primarily by fringe processes. Snapshot data from a multilevel sampling well transect across an MTBE plume at Vandenberg Air Force Base, CA, USA, illustrate the difficulty of centreline monitoring and the challenge of providing sufficient detail to detect attenuation processes that may be occurring primarily at plume fringes. In a study of a phenols plume in Wolverhampton, UK, high-resolution multilevel wells demonstrated that the key biodegradation processes were restricted spatially to the upper fringe of the plume and were rate-limited by transverse dispersion and diffusion of electron acceptors into the plume. Thus the overall extent of biodegradation was considerably less than suggested by a plume-scale analysis of total electron acceptor and contaminant budgets. These examples indicate that more robust and cost-effective MNA assessments can be obtained using monitoring strategies that focus on the location of key biodegradation processes.

Aerobiosis↗

Shifts in archaeal communities associated with lithological and geochemical variations in subsurface Cretaceous rock.

Subsurface microbial community structure in relation to geochemical gradients and lithology was investigated using a combination of molecular phylogenetic and geochemical analyses. Discreet groundwater and substratum samples were obtained from depths ranging from 182 to 190 m beneath the surface at approximately 10-cm intervals using a multilevel sampler (MLS) that straddled Cretaceous shale and sandstone formations at a site in the southern San Juan Basin in New Mexico. DNA and RNA were extracted directly from quartzite sand substratum loaded into individual cells of the MLS and colonized in situ. Polymerase chain reaction (PCR)-mediated T-RFLP analysis of archaeal rRNA genes (rDNA) in conjunction with partial sequencing analysis of archaeal rDNA libraries and quantitative RNA hybridization with oligonucleotide probes were used to probe community structure and function. Although total microbial populations remained relatively constant over the entire depth interval sampled, significant shifts in archaeal populations, predominantly methanogens, were observed. These shifts coincided with the geochemical transition from relatively high methane (26 mM), low sulphate (< 3 mg l(-1)) conditions in the region adjacent to the organic matter-rich shale to relatively low-methane (< 0.5 mM), high-sulphate (48 mg l(-1)) conditions in the organic-poor sandstone beneath the shale. These results indicated that active, phylogenetically diverse archaeal communities were present in the subsurface Cretaceous rock environment at this site and that major archaeal clades shifted dramatically over scales of tens of centimetres, corresponding to changes in the lithology and geochemical gradients.

Archaea↗

An improved micromethod for vancomycin determination by high-performance liquid chromatography.

A micromethod using reversed-phase high-performance liquid chromatography for the analysis of vancomycin in human serum or plasma was developed. Ristocetin was used as the internal standard. Chromatographic conditions included an amino propyl column, a mobile phase with 62% acetonitrile and 38% sodium phosphate buffer (pH 7.0), a total run time of 10 min, and ultraviolet absorbance detection at 225 nm. Multilevel calibration was found to be linear between 1.0 and 100 micrograms/ml with correlation coefficients of the calibration line slope consistently > 0.999. Recovery of vancomycin from serum was nearly complete, and no interference from commonly used drugs was observed. This procedure is simple, sensitive, rapid, precise, selective, and requires only 50 microliters of serum or plasma for completion.

Anti-Bacterial Agents↗

Noninvasive evaluation of mitral regurgitation by analysis of left atrial signal loss in cine magnetic resonance.

Magnetic resonance imaging that uses shallow flip angles, short repetition times, and gradient refocused echoes results in multiple images throughout the cardiac cycle in which the blood pool has high signal intensity. In cine magnetic resonance images, disturbed (high velocity) blood flow produces a loss of signal intensity within the intracavitary blood pool, which makes this technique potentially useful for evaluating valvular disease. Multilevel cine magnetic resonance imaging was performed in 26 patients with mitral regurgitation (MR) documented and graded for severity by Doppler echocardiography or contrast ventriculography. Intracavitary left atrial signal intensity was analyzed in order to derive parameters that reflect the severity of the lesion. Seven normal volunteers were studied for comparison. All regurgitant lesions were visualized in cine magnetic resonance images as discrete regions of systolic signal loss extending from the mitral valve into the left atrium. The extent and degree of signal loss correlated well with severity. In patients with mild MR, signal loss was seen in 3.3 +/- 1.2 (+/- SD) anatomic levels compared to 4.9 +/- 1.4 levels in patients with moderate MR (p = NS), and in 7.0 +/- 1.4 levels in patients with severe MR (p less than 0.001 versus mild MR). The total area of maximal systolic left atrial signal loss seen in all levels was 10 +/- 6 cm2 in mild versus 31 +/- 17 cm2 in moderate (p less than 0.001) and 96 +/- 30 cm2 in severe MR (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High local unemployment and increased mortality in Danish adults; results from a prospective multilevel study.

AIMS: To examine the relation between unemployment rates in area of residence and all-cause mortality, taking the individuals' unemployment experience and a number of social and behavioural factors into account. METHODS: Prospective cohort study with record linkage to mortality and unemployment registers. Data were pooled data from two population studies conducted in Copenhagen, Denmark. The association between unemployment at parish level and mortality was examined in Cox proportional hazard analysis. A total of 15 980 men and women, aged 20-67 years and employed at 1 January 1980, were studied. All-cause mortality was followed from January 1981 to December 1998. RESULTS: The unemployment rate in the area of residence was associated with increased mortality (hazard ratio(highest v lowest quartile) 1.35:0.14-1.60) even after adjustment for individuals' unemployment experience in 1980, which was also a risk factor (hazard ratio(yes/no) 1.38:1.16-1.64). These estimates attenuated somewhat when other social and behavioural covariates were taken into account. The effects were similar in men and women, but the influence of individuals' unemployment experience during one and five years decreased gradually with increasing age. CONCLUSION: This prospective study suggests that high local unemployment and individuals' experience of unemployment increase mortality risk, even after adjustment for other social and behavioural factors.

Adult↗