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Effect of distal occlusions on the assessment of aorto-iliac pathology by analysis of Doppler spectra.

In patients with multilevel arterial obstructive disease, assessment of the severity and location of the pathology is a difficult diagnostic problem. As reported recently, the intra-arterial pressure in the common femoral artery may become normal, although aorto-iliac obstructive disease is present if the superficial femoral artery is occluded. Aorto-iliac obstructive disease can also be assessed by analysis of Doppler spectra obtained from the common femoral artery. In this study, we evaluate if this assessment of aorto-iliac obstructive disease is also harmfully affected by an occlusion in the superficial femoral artery. The results of this study demonstrate that some Doppler parameters (such as acceleration time, slope of the acceleration phase, and the resistance index), which are essential for the assessment of aorto-iliac obstructive disease, are not significantly affected by an occlusion in the superficial femoral artery. Moreover, the study shows that the status of the superficial femoral artery may also be assessed by analysis of Doppler spectra obtained from the common femoral artery.

Adult↗

Estimating effects of latent and measured genotypes in multilevel models.

Multilevel modelling is a data analysis technique for analysing linear models in samples with a hierarchical or clustered structure. Clustered data are often present in genetic research where family members may either be required or serve a methodological purpose to study hereditary factors. These samples imply a natural hierarchy because genetically related individuals are grouped within families. We first demonstrate the use of multilevel modelling to study latent genetic and environmental components of variance in extended families where subjects may be related as twins, full siblings, half siblings, or cousins. Next, measured genotypes are included to estimate locus effects. Because the model accounts for the clustering of observations by estimating a random intercept at the family level, it tests for genotype effects on the phenotype within families so that possible population stratification effects cannot cause false positive results. Several extensions are discussed such as testing for genotype-environment interactions, analysing different types of response scales, or tailoring the model to other sample structures. To illustrate the approach we used birth weight data of 5562 children from 3643 fathers from 3186 mothers in 2873 extended families to which simulated genotypes of a hypothetical locus were added.

Adult↗

A cost analysis of two anterior cervical fusion procedures.

Multilevel anterior cervical discectomy and fusion (ACDF) remains a difficult problem. A recently described surgical technique for multilevel ACDF has eliminated the morbid complications associated with harvesting iliac crest bone graft (ICBG) while maintaining the advantages of using autologous bone graft. A matched-pairs t test was used to compare the estimated costs of 27 ACDFs using titanium surgical mesh, local autologous bone graft, and anterior plate instrumentation with 27 ACDFs using ICBG and plate fixation. The three variables considered were cage cost, operating time (cost), and hospitalization cost. The estimated costs for the two surgical procedures were not significantly different. Thus, the time saved by not harvesting an ICBG was comparable to the cost of the cage. Harvesting ICBG also increased the morbidity rate by 22%.

Bone Transplantation↗

Social disparities in housing and related pediatric injury: a multilevel study.

OBJECTIVES: We conducted an ecologic analysis to determine whether housing characteristics mediate the associations between concentration of poverty and pediatric injury and between concentration of racial minorities and pediatric injury and whether the association between housing conditions and pediatric injury is independent of other risks. METHODS: We created a hierarchical data set by linking individual-level data for pediatric injury with census data. Effect sizes were estimated with a Poisson model. RESULTS: After adjustment for owner occupancy and the percentage of housing built before 1950, the association between concentration of poverty and pediatric injury was attenuated. For concentration of racial minorities, only percentage of owner occupancy had some mediating effect. In hierarchical models, housing characteristics remained independent and significant predictors of pediatric injury. CONCLUSIONS: The association between community characteristics and pediatric injury is partially mediated by housing conditions. Risk of pediatric injury associated with housing conditions is independent of other risks.

Accidental Falls↗

Modified open-door laminoplasty for treatment of neurological deficits in younger patients with congenital spinal stenosis: analysis of clinical and radiographic data.

OBJECT: Multilevel anterior cervical decompressive surgery and fusion effectively treats cervical myeloradiculopathy that is caused by severe cervical spinal stenosis, but degenerative changes at adjacent vertebral levels frequently result in long-term morbidity. The authors performed a modified open-door laminoplasty procedure in which allograft bone and titanium miniplates were used to treat cervical myeloradiculopathy in younger patients with congenital canal stenosis while maintaining functional cervical motion segments. Pre- and postoperative magnetic resonance imaging and/or computerized tomography myelography were performed to assess changes in cervical spinal canal dimensions. Pre- and postoperative flexion-extension radiographs were compared to determine the residual motion of the targeted operative segments. METHODS: Twenty younger patients (average age 37.7 years) underwent modified open-door laminoplasty for treatment of myelopathy or myeloradiculopathy related to significant cervical spinal stenosis with or without associated central or lateral disc herniation or foraminal stenosis. These surgeries were performed during a 2-year period and follow-up review remains ongoing (average follow-up period 21.6 months). Reconstructive procedures were performed on an average of 4.1 levels (range three-six). Operative time averaged 186 minutes (range 93-229 minutes). Average blood loss was 305 ml (range 100-650 ml). No cases were complicated by neurological deterioration, infection, wound breakdown, graft displacement, or hardware failure. The patients' Nurick Scale grade improved from a preoperative average of 1.8 to a postoperative average of 0.5. Pre- and postoperative sagittal spinal diameter averaged 11.2 mm (8-14 mm) and 16.6 mm (13-19 mm), respectively. The sagittal compression ratio (sagittal/lateral x 100%) increased from 48% pre- to 72% postoperatively. The spinal canal area increased an average of 55% (range 19-127%). In patients in whom pre- and postoperative flexion-extension radiographs were obtained, 72.7% residual neck motion was maintained. No patient developed increased neck or shoulder pain. Neurological symptoms improved in all patients, with total relief of myelopathy in 50% and partial improvement in 50%. CONCLUSIONS: Modified open-door laminoplasty with allograft bone and titanium miniplates effectively treats neurological deficits in younger patients with congenital and spinal stenosis. Although long-term results are unknown, short-term results are good and there is a low incidence of complications.

Adult↗

A review of multilevel theory for ecologic analyses.

This paper reviews multilevel and conventional models for the analysis of ecologic (group, aggregate) data. It emphasizes the non-separability of contextual (group-level) effects and individual-level effects that arises from the multilevel structure of the underlying effects. Contrary to common misperceptions, this problem afflicts ecologic studies in which the sole objective is to estimate contextual effects, as well as studies in which the objective is to estimate individual effects. Multilevel effects also severely complicate causal interpretations of model coefficients.

Bias↗

Methodological issues in health human resource planning: cataloguing assumptions and controlling for variables in needs-based modelling.

Health Human Resource Planning (HHRP) models approximate future nursing requirements based on a variety of factors specific to the model being employed. There is an urgent need to develop a better understanding of the sources of bias in statistical modelling in order to ensure that we are guided by accurate and robust formulae. This paper addresses these issues as they apply in the context of needs-based HHRP research for nursing by presenting a review and discussion of the relevant literature as it relates to: (1) the testing of assumptions, (2) avoiding ecological and atomistic fallacies, (3) how need is directly or indirectly related to health care, and (4) alternatives to aggregate analysis for assessing the relationship between health needs and utilization of nursing services. The paper concludes that multilevel modelling is useful for the simulation analysis of individuals and their ecologies, and that small area variation modelling holds promise for assessing the relationship between health needs and utilization of nursing services.

Canada↗

Closed transventricular aortic valvotomy for critical aortic stenosis in neonates: outcomes, risk factors, and reoperations.

BACKGROUND: Critical aortic stenosis (AS) in neonates necessitates urgent intervention for patient survival. The optimal treatment, however, continues to be controversial and still has high morbidity and mortality in many centers. This study examined our late outcome, risks, and reoperations after the treatment of critical AS in neonates. METHODS: Sixty-six neonates (47 boys and 19 girls) underwent closed transventricular aortic valvotomy for critical AS between 1978 and 2000. The mean age at the first intervention was 15.1 +/- 19.6 days (range, 1 to 78). Their weight ranged from 1.4 to 6.2 kg (mean, 3.5 +/- 0.9 kg). Sixteen patients (23%) had isolated critical AS and normal or dilated left ventricles, and 50 neonates (77%) had associated cardiovascular anomalies (ie, aortic annular hypoplasia, hypoplasia of the left ventricle, mitral valve abnormalities, and endocardial fibroelastosis, coarctation, or interruption of aorta). RESULTS: The hospital mortality was 29% (19 of 66). Kaplan-Meier 5- and 15-year survival was 61% and 58%, respectively. The operative mortality rates were 6% in neonates with isolated AS and 36% in patients with complex AS. The five risk factors significant for mortality on univariate analysis were (1) presence of endocardial fibroelastosis (p = 0.05), (2) presence of hypoplastic left ventricle (p = 0.003), (3) presence of associated cardiovascular anomalies (p = 0.04), (4) aortic valve annulus of less than 5.0 mm (p = 0.01), and (5) surgery before 1985 (p = 0.003). Of these five factors, only the presence of hypoplastic left ventricle (p = 0.001) and surgery before 1985 (p = 0.001) remain significant for mortality by multivariate analysis. At last follow-up (mean, 8.2 +/- 6.2 years), 36 of 47 of the long-term survivors were in New York Heart Association functional class I and II. Kaplan-Meier analysis showed 5- and 15-year freedom from aortic valve reoperation to be 83% and 60%, respectively. Univariate and multivariate analysis showed the presence of multilevel stenosis (p = 0.04) as the best preoperative predictor for the need for late reoperation in survivors. CONCLUSIONS: We conclude that critical AS in neonates continues to be associated with significant mortality. Reintervention such as surgical and balloon valvotomy are usually required within 10 years of initial surgery.

Alprostadil↗

Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia.

BACKGROUND: Although liability to psychosis is thought to have its origins in cerebral alterations, expressed as cerebral grey and white matter loss, less is known about the degree to which such vulnerabilities impact on functional parameters, in particular altered stress reactivity. Breier et al. [Breier, A., Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541-550] reported that lower prefrontal cortex volume was associated with altered metabolic stress response, but this finding has never been replicated. METHODS: Thirty-one patients with psychosis underwent structural magnetic resonance imaging scanning and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition versus placebo condition) that yielded information on plasma homovanillic acid (HVA) reactivity. Total cerebral tissue volumes were derived from automated segmentation procedures. Associations between metabolic stress and tissue volumes (as well as their interactions) on the one hand, and plasma HVA level on the other, were investigated using multilevel random regression techniques. RESULTS: Analysis revealed a significant increase in plasma HVA over time in the 2DG condition. The increase in HVA in the stress condition was stronger in patients with lower grey and white matter volumes. There was no significant interaction between metabolic stress and CSF volume. CONCLUSION: Lower grey and white matter volumes in schizophrenia are associated with a dysregulated dopaminergic/noradrenergic mediated stress response. These findings may support the hypothesis that alterations in cortico-subcortical connections affect psychosis susceptibility through an altered stress response.

Adolescent↗

[Optimizing history taking for evaluating the risk of venous thromboembolism: the OPTIMEV study].

UNLABELLED: Venous thromboembolism (VTE) is a frequent disease and remains a major cause of mortality and morbidity among our patients. During the 20 past years, clinical description, diagnostic tools, and treatment have changed dramatically. Most published data describing risk factors for VTE no longer apply to the patients seen in daily practice. We present here the rationale, aims, and methodology of the OPTIMEV Study (OPTimisation de l'Interrogatoire pour la Maladie thromboEmbolique Veineuse). RATIONALE: Risk factors for VTE are numerous, complex and interactions between them and their clinical importance is difficult to measure (table I). For example, odds ratios for VTE recurrence vary greatly across longitudinal studies. We searched the National Library of Medecine (PubMed) and the Amedeo website using the following keywords: "venous thromboembolism", "pulmonary embolism", "deep vein thrombosis", "risk factors". We selected 84 relevant articles published between 1972 and 2005. Based on this literature analysis, we identified the following major risk factors: VTE recurrence, surgery, cancer, immobilization, age, biological factors. For these factors, data are lacking and some questions are proposed. OBJECTIVES: The broad objective of the study is to better evaluate clinical risk factors that fit today's practice against VTE. Specific aims are: 1) to determine whether risk factors are different between proximal and distal deep vein thrombosis (DVT); 2) to develop and prospectively validate a new prediction rule for outpatients. The primary hypothesis is that careful assessment of VTE recurrence, adequate surgical thromboprophylaxis, cancer staging, and varicose vein stratification according to the CEAP classification, is mandatory for accurate evaluation of thromboembolic disease risk. METHODS: We conducted a multicenter, prospective, cohort study of 10000 patients. Enrollees are inpatients and outpatients presenting with a clinical suspicion of VTE in Emergency Departments and outpatient clinics in France. 4173 patients have been enrolled at this time (Figure 2). All eligible patients are enrolled during a selected period of time through different seasons. Data are collected by physicians in charge of the patients using an electronic case recording form. Collected data include baseline characteristics, risk factors, results of diagnostic investigations. Outcome measures obtained through telephone interview at 3 and 12 months include cancer diagnosis, VTE recurrence, haemorrhagic events, treatments, death. Univariate and multivariate analysis will be performed using multilevel logistic regression. The study organization is performed by the Centre d'Investigation Clinique de Grenoble and is sponsored by the French Society of Vascular Medicine. First results, to be published in 2006, will allow development of new prediction rules for VTE diagnosis.

Age Factors↗

Triplet ultrasound growth parameters.

OBJECTIVE: To create ultrasound growth curves for normal growth of fetal triplets using statistical methodology that properly accounts for similarities of growth of fetuses within a mother as well as repeated measurements over time for each fetus. METHODS: In this longitudinal study, all triplet pregnancies managed at a single tertiary center from 1992-2004 were reviewed. Fetuses with major anomalies, prior selective reduction, or fetal demise were excluded. Data from early and late gestation in which there were fewer than 30 fetal measurements available for analysis were excluded. We used multilevel models to account for variation in growth within a single fetus over time, variations in growth between multiple fetuses within a single mother, and variations in fetal growth between mothers. Medians (50th), 10th, and 90th percentiles were estimated by the creation of multiple quadratic growth models from bootstrap samples adapting a previously published method to compute prediction intervals. Estimated fetal weight was derived from Hadlock's formula. RESULTS: One hundred fifty triplet pregnancies were identified. Twenty-seven pregnancies were excluded for the following reasons: missing records (23), fetal demise (3), and fetal anomaly (1). The study group consisted of 123 pregnancies. The gestational age range was restricted to 14-34 weeks. Figures and tables were developed showing medians, 10th and 90th percentiles for estimated fetal weight, femur length, biparietal diameter, abdominal circumference, and head circumference. CONCLUSION: Growth curves for triplet pregnancies were derived. These may be useful for identification of abnormal growth in triplet fetuses. LEVEL OF EVIDENCE: III.

Anthropometry↗

Static and dynamic longitudinal structural analyses of cognitive changes in old age.

BACKGROUND: Among the main data-analytical advances of recent decades are Latent Growth Models (LGM) and Multilevel Models (MLM) for the analysis of longitudinal data. OBJECTIVE: We discuss the relative advantages and disadvantages of the two analytical methods and offer some practical guidelines concerning the choice between LGM and MLM based on (a). completeness and balance of the data, (b). theoretical functional form of change examined, (c). examination of the error structure, (d). theoretical relations among differential level effects and differential change effects, and (e). role of time-invariant covariates. METHODS: To discuss LGM and MLM, we provide illustrations from applications to the Berlin Aging Study (BASE) and the Swiss Interdisciplinary Longitudinal Study on the Oldest Old (SWILSO-O). RESULTS: As predicted by two-component theories of lifespan cognition, performance on a vocabulary test (indicator of broad crystallized intelligence) did not decline over time, while scores on a digit letter test (indicator of broad fluid intelligence) decreased over 6 years. Differential level effects were obtained on both variables, while average and differential change effects were obtained only for the digit letter test. In a second set of analyses, we tested the error-free effect that a broad fluid intelligence indicator exerted on the latent yearly change in a broad crystallized intelligence indicator, and vice versa. In both data sets we obtained strong evidence for a more reliable effect of the fluid indicator on the change in the crystallized indicator. This evidence provided support for the dedifferentiation hypothesis of cognitive abilities in very old age. CONCLUSIONS: New insights into cognitive aging phenomena can be gained with proper applications of LGM and MLM. We posit that the choice between LGM and MLM and their specification rests on theoretical and empirical motives to be defined a priori.

Aging↗

Genetic determinants of C-reactive protein in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with a systemic inflammatory state, marked by elevations in serum inflammatory markers including C-reactive protein (CRP). The present study sought to determine epidemiological predictors of CRP levels, to estimate the genetic influence on CRP levels, and to identify genetic variants that affect CRP in a family-based study of COPD. CRP was measured by a high-sensitivity assay in participants from the Boston Early-Onset COPD Study. Predictors of CRP level were determined using multilevel linear models. Variance component analysis was used to estimate heritability and to perform genome-wide linkage analysis for CRP levels. Two variants in the surfactant protein B (SFTPB) gene were tested for association with CRP levels. Increased age, female sex, higher body mass index, greater smoking pack-yrs and reduced forced expiratory volume in one second were all associated with increased CRP levels. There was a significant genetic influence on CRP (heritability = 0.25). Genome-wide linkage analysis revealed several potentially interesting chromosomal regions, though no significant evidence for linkage was found. A short tandem repeat marker near SFTPB was significantly associated with CRP levels. There is a genetic influence on C-reactive protein levels in chronic obstructive pulmonary disease patients. Preliminary evidence suggests an association of the surfactant protein B gene with systemic inflammation in chronic obstructive pulmonary disease.

C-Reactive Protein↗

Using multilevel modeling in caregiving research.

Recently, caregiving research has moved towards a greater emphasis on the interactive and dynamic processes of the care situation. As a result, many of the questions are multilevel in nature, involving more than one unit of analysis and placing greater focus on the context of the care dyad. Nevertheless, most caregiving studies use methods that fail to address the hierarchical nature of the care dyad and consequently fail to illuminate variation both within and between dyad processes. The focus of this paper is to promote a dyad approach to the analysis of caregiving data and to highlight the advantages and appropriateness of multilevel modeling when dealing with clustered or hierarchical data. In particular, we discuss how multilevel modeling can be adapted to study change in the care dyad over time, improve the way we evaluate interventions, and enhance our understanding of dyad congruence.

Aging↗

Multilevel modelling of the geographical distributions of diseases.

"Multilevel modelling is used on problems arising from the analysis of spatially distributed health data. We use three applications to demonstrate the use of multilevel modelling in this area. The first concerns small area all-cause mortality rates from Glasgow where spatial autocorrelation between residuals is examined. The second analysis is of prostate cancer cases in Scottish counties where we use a range of models to examine whether the incidence is higher in more rural areas. The third develops a multiple-cause model in which deaths from cancer and cardiovascular disease in Glasgow are examined simultaneously in a spatial model. We discuss some of the issues surrounding the use of complex spatial models and the potential for future developments."

Cause of Death↗

The treatment of disabling multilevel lumbar discogenic low back pain with total disc arthroplasty utilizing the ProDisc prosthesis: a prospective study with 2-year minimum follow-up.

STUDY DESIGN: Prospective, longitudinal minimum 2-year follow-up. OBJECTIVE: To assess the efficacy and safety of the Prodisc implant in patients with disabling multilevel discogenic low back pain (LBP). SUMMARY OF BACKGROUND DATA: Few, if any, alternatives have been proposed to treat recalcitrant and debilitating multilevel lumbar discogenic low back pain. To date, a prospective study specifically examining the use of multilevel Prodisc total disc arthroplasty has not been described. METHODS: A prospective analysis was performed on 25 patients (63 prostheses) treated with multilevel lumbar ProDisc total disc arthroplasty. Minimum follow-up was 2 years. Patients 18 to 60 years of age with disabling discogenic low back pain and minimal radicular pain secondary to multiple level lumbar spondylosis from L1 to S1 were included. Preoperative and postoperative disability and pain scores were measured using Oswestry and visual analog scores. Preoperative and postoperative neurologic, radiographic, and pain medication assessments were also performed at similar postoperative intervals. RESULTS: A total of 29 patients (72 prostheses) were enrolled in the prospective analysis. Twenty-five patients (63 prostheses) fulfilled all follow-up criteria and are included for final analysis. Fifteen bisegmental and 10 trisegmental level cases were performed. Visual analog pain, Oswestry, and patient satisfaction scores were significantly reduced at the 3-month as well as at 48-month follow-up. Radiographic analysis revealed an affected disc height increases from 5 mm to 12 mm (P < 0.05) and affected disc motions from 3 degrees to 7 degrees (P < 0.05). No change in adjacent level disc heights was seen. Complications included a single case of subsidence of the inferior endplate of the L4-L5 segment in a bisegmental L4-L5/L5-S1 case. We also report a delayed case of anterior extrusion of a polyethylene component in a patient who had sustained a fall of a bicycle. CONCLUSIONS: Our preliminary data on multisegmental ProDisc lumbar total disc arthroplasty appear to be a safe and efficacious treatment method for debilitating lumbar spondylosis without significant facet arthropathy. In our select (non-Workers Compensation and/or medical legal) cohort of patients, we demonstrate a patient satisfaction rate of 93%. Careful and appropriate patient selection is essential in ensuring optimal surgical outcomes.

Adult↗

Sentinel lymph node biopsy is not accurate in predicting lymph node status for patients with cervical carcinoma.

BACKGROUND: The authors evaluated the accuracy of sentinel lymph node biopsy in predicting lymph node status for patients with early cervical carcinoma. In particular, the authors set out to determine the false-negative rate associated with sentinel lymph node biopsy in this setting. METHODS: Twenty-nine consecutive patients with early cervical carcinoma who were treated with pelvic laparoscopic lymphadenectomy and radical surgery underwent sentinel lymph node biopsy following lymphatic mapping with patent blue dye. All sentinel and nonsentinel lymph nodes were evaluated for micrometastases via multilevel sectioning followed by immunohistochemical staining. RESULTS: At least one sentinel lymph node was identified for each patient. On routine pathologic evaluation, 3 patients (10%) were found to have positive lymph nodes. Among the remaining 26 patients, multilevel sectioning in conjunction with immunohistochemical analysis identified 5 patients (19%) who had micrometastases in the pelvic lymph nodes. Two of these five patients had micrometastases in a sentinel lymph node; however, the more notable finding was that the other three patients had micrometastases in nonsentinel pelvic lymph nodes despite having negative findings on sentinel lymph node biopsy. Thus, the negative predictive value of sentinel lymph node biopsy in the current study was 87.5%. CONCLUSIONS: Multilevel sectioning followed by cytokeratin immunohistochemistry may identify additional patients who have lymph node micrometastases; in the current study, this technique identified cases in which micrometastases were present in nonsentinel lymph nodes even when sentinel lymph nodes were found to be negative for disease on biopsy. This high false-negative rate associated with sentinel lymph node biopsy, raises questions regarding the validity of the sentinel lymph node concept in cervical carcinoma.

Adenocarcinoma↗