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PubMed2004

Clinical and genetic characteristics of hereditary pancreatitis in Europe.

BACKGROUND & AIMS: Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe. METHODS: Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling. RESULTS: There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%). CONCLUSIONS: Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.

Adult↗
PubMed2004

Hindbrain catecholamine neurons mediate consummatory responses to glucoprivation.

Previous work using the retrogradely transported immunotoxin, saporin (SAP) conjugated to a monoclonal antibody against dopamine-beta-hydroxylase (DBH; DSAP), to selectively lesion norepinephrine (NE) and epinephrine (E) neurons projecting to the medial hypothalamus, demonstrated the essential role of these neurons for appetitive ingestive responses to glucoprivation. Here, we again utilized this lesion to assess the importance of these same neurons for the consummatory phase of glucoprivic feeding. To test consummatory responses, milk was infused intraorally through a chronic cheek fistula until rejected. Appetitive responses were tested in the same rats using pelleted food. Feeding responses to insulin-induced hypoglycemia, 2-deoxy-D-glucose (2DG)-induced blockade of glucose utilization, mercaptoacetate (MA)-induced blockade of fatty acid oxidation, 0.9% saline, and 18-h food deprivation were assessed. Unlike unconjugated SAP controls, the DSAP rats did not increase their food intake in response to glucoprivic challenges in either the pelleted food or the intraoral feeding tests. However, the DSAP rats did not differ from SAPs in their ingestive responses to food deprivation and blockade of fatty acid oxidation. The selective impairment of glucoprivic feeding responses indicates that DSAP did not impair the underlying circuitry required for either appetitive or consummatory ingestive responding but eliminated the mechanism for control of this circuitry specifically by glucoprivation. Results suggest that both appetitive and consummatory responses to glucoprivation are controlled and coordinated by multilevel terminations of the same catecholamine neurons.

Analysis of Variance↗
PubMed1999

A general maximum likelihood analysis of variance components in generalized linear models.

This paper describes an EM algorithm for nonparametric maximum likelihood (ML) estimation in generalized linear models with variance component structure. The algorithm provides an alternative analysis to approximate MQL and PQL analyses (McGilchrist and Aisbett, 1991, Biometrical Journal 33, 131-141; Breslow and Clayton, 1993; Journal of the American Statistical Association 88, 9-25; McGilchrist, 1994, Journal of the Royal Statistical Society, Series B 56, 61-69; Goldstein, 1995, Multilevel Statistical Models) and to GEE analyses (Liang and Zeger, 1986, Biometrika 73, 13-22). The algorithm, first given by Hinde and Wood (1987, in Longitudinal Data Analysis, 110-126), is a generalization of that for random effect models for overdispersion in generalized linear models, described in Aitkin (1996, Statistics and Computing 6, 251-262). The algorithm is initially derived as a form of Gaussian quadrature assuming a normal mixing distribution, but with only slight variation it can be used for a completely unknown mixing distribution, giving a straightforward method for the fully nonparametric ML estimation of this distribution. This is of value because the ML estimates of the GLM parameters can be sensitive to the specification of a parametric form for the mixing distribution. The nonparametric analysis can be extended straightforwardly to general random parameter models, with full NPML estimation of the joint distribution of the random parameters. This can produce substantial computational saving compared with full numerical integration over a specified parametric distribution for the random parameters. A simple method is described for obtaining correct standard errors for parameter estimates when using the EM algorithm. Several examples are discussed involving simple variance component and longitudinal models, and small-area estimation.

Adrenergic beta-Antagonists↗
PubMed2007

Multilevel models for estimating incremental net benefits in multinational studies.

Multilevel models (MLMs) have been recommended for estimating incremental net benefits (INBs) in multicentre cost-effectiveness analysis (CEA). However, these models have assumed that the INBs are exchangeable and that there is a common variance across all centres. This paper examines the plausibility of these assumptions by comparing various MLMs for estimating the mean INB in a multinational CEA. The results showed that the MLMs that assumed the INBs were exchangeable and had a common variance led to incorrect inferences. The MLMs that included covariates to allow for systematic differences across the centres, and estimated different variances in each centre, made more plausible assumptions, fitted the data better and led to more appropriate inferences. We conclude that the validity of assumptions underlying MLMs used in CEA need to be critically evaluated before reliable conclusions can be drawn.

Cost-Benefit Analysis↗
PubMedDate not supplied

Vertical cross contamination of trichloroethylene in a borehole in fractured sandstone.

Boreholes drilled through contaminated zones in fractured rock create the potential for vertical movement of contaminated ground water between fractures. The usual assumption is that purging eliminates cross contamination; however, the results of a field study conducted in a trichloroethylene (TCE) plume in fractured sandstone with a mean matrix porosity of 13% demonstrates that matrix-diffusion effects can be strong and persistent. A deep borehole was drilled to 110 m below ground surface (mbgs) near a shallow bedrock well containing high TCE concentrations. The borehole was cored continuously to collect closely spaced samples of rock for analysis of TCE concentrations. Geophysical logging and flowmetering were conducted in the open borehole, and a removable multilevel monitoring system was installed to provide hydraulic-head and ground water samples from discrete fracture zones. The borehole was later reamed to complete a well screened from 89 to 100 mbgs; persistent TCE concentrations at this depth ranged from 2100 to 33,000 microg/L. Rock-core analyses, combined with the other types of borehole information, show that nearly all of this deep contamination was due to the lingering effects of the downward flow of dissolved TCE from shallower depths during the few days of open-hole conditions that existed prior to installation of the multilevel system. This study demonstrates that transfer of contaminant mass to the matrix by diffusion can cause severe cross contamination effects in sedimentary rocks, but these effects generally are not identified from information normally obtained in fractured-rock investigations, resulting in potential misinterpretation of site conditions.

California↗
PubMed2005

Healthy eating and exercising to reduce diabetes: exploring the potential of social determinants of health frameworks within the context of community-based participatory diabetes prevention.

OBJECTIVES: We examined a community-based participatory diabetes intervention to identify facilitators of and barriers to sustained community efforts to address social factors that contribute to health. METHODS: We conducted a case study description and analysis of the Healthy Eating and Exercising to Reduce Diabetes project in the theoretical context of a conceptual model of social determinants of health. RESULTS: We identified several barriers to and facilitators of analysis of social determinants of a community-identified disease priority (in this case, diabetes). Barriers included prevailing conceptual models, which emphasize health behavioral and biomedical paradigms that exclude social determinants of health. Facilitating factors included (1) opportunities to link individual health concerns to social contexts and (2) availability of support from diverse partners with a range of complementary resources. CONCLUSIONS: Partnerships that offer community members tangible resources with which to manage existing health concerns and that integrate an analysis of social determinants of health can facilitate sustained engagement of community members and health professionals in multilevel efforts to address health disparities.

Adult↗
PubMed1998

Carotid atherosclerosis in patients operated for lower extremity ischemia before the age of 50: a case control study.

The purpose of this study was to investigate the presence of, and to identify factors associated with carotid atherosclerosis in patients, previously operated on for lower extremity ischemia before the age of 50. Forty-eight patients were compared to sex- and age-matched controls. All subjects were examined with duplex ultrasonography of the neck arteries and analysis of serum lipoproteins. History including smoking habits, family history of cardiovascular disease, and medication was also obtained. The patients were examined clinically and their preoperative angiograms were reevaluated. Thirty-one patients (64%) and 13 controls (23%) had a carotid lesion (p < 0.0001). Patients with suprainguinal or multilevel disease had a higher proportion of carotid lesions than those with only infrainguinal disease in whom the proportion was similar to the controls. A multiple regression analysis among the patients revealed that age, level of lower extremity arterial disease, presence of family history, and the ratio apolipoproteinB/apolipoproteinA discriminated significantly between those with and without carotid disease. It is concluded that a high proportion of patients operated on for lower extremity suprainguinal arterial occlusive disease at an early age have carotid lesions at follow-up, while patients operated on due to isolated infrainguinal disease have a prevalence similar to controls.

Arteriosclerosis↗
PubMed2005

The relationship between childbearing and transitions from marriage and cohabitation in Britain.

In this article, we describe a general framework for the analysis of correlated event histories, with an application to a study of partnership transitions and fertility among a cohort of British women. Using a multilevel, multistate competing-risks model, we examine the relationship between prior fertility outcomes (the presence and characteristics of children and current pregnancy) and the dissolution of marital and cohabiting unions and movements from cohabitation to marriage. Using a simultaneous-equations model, we model these partnership transitions jointly with fertility, allowing for correlation between the unobserved woman-level characteristics that affect each process. The analysis is based on the partnership and birth histories that were collected for the 1958 birth cohort (National Child Development Study) aged 16-42. The findings indicate that preschool children have a stabilizing effect on their parents 'partnership, whether married or cohabiting, but the effect is weaker for older children. There is also evidence that although pregnancy precipitates marriage among cohabitors, the odds of marriage decline to prepregnancy levels following a birth.

Adolescent↗
PubMed2005

Multilevel orthopaedic surgery in group IV spastic hemiplegia.

Most children with spastic hemiplegia have high levels of function and independence but fixed deformities and gait abnormalities are common. The classification proposed by Winters et al is widely used to interpret hemiplegic gait patterns and plan intervention. However, this classification is based on sagittal kinematics and fails to consider important abnormalities in the transverse plane. Using three-dimensional gait analysis, we studied the incidence of transverse-plane deformity and gait abnormality in 17 children with group IV hemiplegia according to Winters et al before and after multilevel orthopaedic surgery. We found that internal rotation of the hip and pelvic retraction were consistent abnormalities of gait in group-IV hemiplegia. A programme of multilevel surgery resulted in predictable improvement in gait and posture, including pelvic retraction. In group IV hemiplegia pelvic retraction appeared in part to be a compensating mechanism to control foot progression in the presence of medial femoral torsion. Correction of this torsion can improve gait symmetry and function.

Adolescent↗
PubMed1988

Sectional and segmental variability of left ventricular function: experimental and clinical studies using ultrafast computed tomography.

In this study, ultrafast computed tomography, a new high spatial and temporal resolution imaging system, was employed to define the range of sectional (tomographic) and segmental left ventricular function in 11 normal anesthetized dogs and 11 normal human volunteers. After intravenous infusion of contrast agent, multilevel tomographic images of the left ventricle (apex to base) were acquired at a rate of 17 frames/s. Analysis of these studies demonstrated substantial but predictable heterogeneity in left ventricular contraction from apex to base. In dogs and humans, for example, the average tomographic ejection fraction of the most basal level of the left ventricle was 40% less than that of the most apical level (p less than 0.05). In humans, circumferential segmental cavity contraction at the mid-papillary muscle level was relatively homogeneous (range 50 to 92% for 12 wedge-shaped segments around the tomographic circumference) if the reference system employed an endocardial centroid, but was less uniform if it used an epicardial centroid (range 22 to 98%). It is concluded that contraction of the normal left ventricle in dogs and humans is heterogeneous both between levels (apex to base) and within a single level (circumferential cavity contraction). However, the patterns of cavity contraction from apex to base and circumferential segmental cavity contraction within a given level as defined by ultrafast computed tomography are sufficiently narrow and predictable in normal individuals that these variables may be useful to define regional contraction abnormalities in pathologic conditions.

Adult↗
PubMed2006

Internal rotation gait in spastic diplegia--critical considerations for the femoral derotation osteotomy.

The purpose of this study was to assess under- and overcorrection following femoral derotation osteotomy (FDO) in spastic diplegic children with functionally compromising internally rotated gait, especially with respect to asymmetry. A total of 30 children with spastic diplegia and internally rotated gait underwent multilevel surgery including FDO and were assessed pre- and 1 year postoperatively by clinical examination and instrumented gait analysis. The amount of derotation was determined intra-operatively based on the neutral midpoint between passive internal and external hip rotation and was controlled with K-wires. Sixteen patients showed an asymmetry in mean hip rotation in stance of more than 10 degrees preoperatively. Accordingly, all legs were classified as the more or the less involved side. Improvement parameters were established for the evaluation of over- and undercorrection. For the clinical midpoint, no significant difference in change and improvement was found between the sides. The mean hip rotation in stance improved significantly in the more involved side with few incidences of mal-correction (13%). The less involved side, however, got worse due to a high occurrence of over- and undercorrections (59%). Hence the clinical midpoint as indication criterion does not give sufficient information about the functional alignment of the distal femur during gait, especially in legs with mild involvement. The study underlines the importance of gait analysis for indication in addition to the clinical midpoint. Taking into account the precision of gait analysis data and derotation amount, we suggest FDO to be carried out if the mean internal hip rotation in stance exceeds 15 degrees .

Adult↗
PubMed2003

The association between state income inequality and worse health is not confounded by race.

BACKGROUND: The relationship between income inequality and health across US states has been challenged recently on grounds that this relationship may be confounded by the effect of racial composition, measured as the proportion of the state's population who are black. METHODS: Using multilevel statistical models, we examined the association between state income inequality and poor self-rated health. The analysis was based on the pooled 1995 and 1997 Current Population Surveys, comprising 201 221 adults nested within 50 US states. RESULTS: Controlling for the individual effects of age, sex, race, marital status, education, income, health insurance coverage, and employment status, we found a significant effect of state income inequality on poor self-rated health. For every 0.05-increase in the Gini coefficient, the odds ratio (OR) of reporting poor health increased by 1.39 (95% CI: 1.26, 1.51). Additionally controlling for the proportion of the state population who are black did not explain away the effect of income inequality (OR = 1.30; 95% CI: 1.15, 1.45). While being black at the individual level was associated with poorer self-rated health, no significant relationship was found between poor self-rated health and the proportion of black residents in a state. CONCLUSION: Our finding demonstrates that neither race, at the individual level, nor racial composition, as measured at the state level, explain away the previously reported association between income inequality and poorer health status in the US.

Adult↗
PubMed2003

Effectiveness of titanium mesh cylindrical cages in anterior column reconstruction after thoracic and lumbar vertebral body resection.

STUDY DESIGN: A retrospective cohort study with cross-sectional outcome analysis of patients who underwent anterior column reconstruction with a titanium mesh cage after single-level or multilevel thoracic or lumbar vertebrectomy. OBJECTIVES: To radiographically evaluate the ability of titanium mesh cages to maintain alignment and facilitate osseous fusion after thoracolumbar vertebrectomy. Secondary objectives assessed complications and patient outcome. SUMMARY OF BACKGROUND DATA: Titanium mesh cages with cancellous autograft bone for postvertebrectomy reconstruction of the thoracolumbar spine avoid some of the potential problems associated with the acquisition or use of structural autograft or allograft. There is little in the literature that describes the efficacy or outcomes of using cylindrical mesh titanium cages for postvertebrectomy reconstruction. METHODS: The degree of kyphosis and the subsidence of the cage in relation to the vertebral endplates were measured in 43 of 57 (75%) patients available at a minimum of 2 years following titanium mesh cage reconstruction. Health-related quality of life and disability were assessed with various cross-sectional outcome measures. RESULTS: The average kyphosis of 25.4 degrees before surgery was reduced to 7.5 degrees immediately after surgery, and at final follow-up was measured to be 10.4 degrees. Cage subsidence averaged 0.28 and 0.20 cage fenestrations at the cephalad and caudal endplates, respectively. Osseous union (Grade 1 or 2) was identified in 93% of radiographs at the final follow-up. Thoracic reconstructions were significantly more likely to require surgical revision because of mechanical failure than thoracolumbar or lumbar reconstructions. CONCLUSION: The cylindrical mesh titanium cage is a successful adjunct in restoring and maintaining sagittal plane alignment after thoracolumbar vertebrectomy and, in this context, provides an effective method for anterior column reconstruction.

Adolescent↗
PubMed2006

Lengthening and transfer of hamstrings for a flexion deformity of the knee in children with bilateral cerebral palsy: technique and preliminary results.

Between July 2000 and April 2004, 19 patients with bilateral spastic cerebral palsy who required an assistive device to walk had combined lengthening-transfer of the medial hamstrings as part of multilevel surgery. A standardised physical examination, measurement of the Functional Mobility Scale score and video or instrumented gait analysis were performed pre- and post-operatively. Static parameters (popliteal angle, flexion deformity of the knee) and sagittal knee kinematic parameters (knee flexion at initial contact, minimum knee flexion during stance, mean knee flexion during stance) were recorded. The mean length of follow-up was 25 months (14 to 45). Statistically significant improvements in static and dynamic outcome parameters were found, corresponding to improvements in gait and functional mobility as determined by the Functional Mobility Scale. Mild hyperextension of the knee during gait developed in two patients and was controlled by adjustment of their ankle-foot orthosis. Residual flexion deformity > 10 degrees occurred in both knees of one patient and was treated by anterior distal femoral physeal stapling. Two children also showed an improvement of one level in the Gross Motor Function Classification System.

Adolescent↗
PubMed1997

"We decide, you carry it out": a social network analysis of multidisciplinary long-term care teams.

The purpose of this study was to describe the structure of multidisciplinary long-term care teams by identifying the pattern of relationships that develop amongst staff as they go about their work. Using a social network analysis approach, team members were classified as occupying the same structural position based on their patterns of relationships with other team members. The analysis was based on the results of a self-administered survey of 93 health care workers on three teams in the same multilevel geriatric care facility in Metropolitan Toronto. A common structure of the teams was identified consisting of two sub-teams: a multiprofessional sub-team and a nursing sub-team, each of which has a different structure indicating differential involvement in different types of teamwork. The multiprofessional sub-team has an "organic" structure and is mainly involved in teamwork that involves decision-making and problem-solving, whereas the nursing sub-team has a "mechanistic" structure and is mainly involved in task oriented work. The findings of this analysis indicate that while teamwork may be increasing the participation in decision-making by health professionals other than medicine, rather than flattening the hierarchical structure throughout the health care division of labour, its effects are limited to a group of higher status professionals. The clearly defined hierarchy remains for the lower status subdisciplines, and "I decide, you carry it out" has simply become "We decide, you carry it out".

Adult↗
PubMed2006

A comparative analysis of the use of maternal health services between teenagers and older mothers in sub-Saharan Africa: evidence from Demographic and Health Surveys (DHS).

This paper uses Demographic and Health Surveys data from 21 countries in sub-Saharan Africa to examine the use of maternal health services by teenagers. A comparison of maternal health care between teenagers and older women, based on bivariate analysis shows little variation in maternal health care by age. However, after controlling for the effect of background factors such as parity, premarital births, educational attainment and urban/rural residence in a multivariate analysis, there is evidence that teenagers have poorer maternal health care than older women with similar background characteristics. The results from multilevel logistic models applied to pooled data across countries show that teenagers are generally more likely to receive inadequate antenatal care and have non-professional deliveries. An examination of country-level variations shows significant differences in the levels of maternal health care across countries. However, there is no evidence of significant variations across countries in the observed patterns of maternal health care by maternal age. This suggests that the observed patterns by maternal age are generalizable across the sub-Saharan Africa region.

Adolescent↗
PubMed2001

Computer-based intraoral image analysis of the clinical plaque removing capacity of 3 manual toothbrushes.

BACKGROUND: (I) Introducing an intraoral camera system with a special positioner to allow computer-based analysis of reproducible images on lingual tooth surfaces and (II) comparing plaque removal by three manual toothbrushes with different brushhead designs (convex, multilevel and flat trimmed) on lingual mandibular tooth surfaces. METHOD: In a clinical single-blind, crossover, 24-h plaque-regrowth study on 25 subjects, a computer-based index (PPI) was used to evaluate pre- and postbrushing plaque on lingual surfaces of mandibular premolars and molars. Subjects brushed their teeth under standardized conditions at three visits, each time with a different, randomly assigned toothbrush. RESULTS: The intraoral camera system allowed a reproducible and relatively convenient access to the lingual surfaces of the mandibular teeth and provided an increase in objectivity. Overall, each brush achieved statistically significant plaque removal, however, none reached clinical relevance. The multilevel brush was superior at specific sites, but failed to show statistically significant superiority in terms of overall plaque reduction. Without regard of the toothbrush used, the right handed subjects were less efficient in removing plaque from the right side compared to the left. CONCLUSIONS: The method is able to detect even small differences in plaque reduction. None of the different brushhead designs was able to compensate an insufficient brushing techniques.

Adult↗