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PubMedDate not supplied

Empirical studies assessing the quality of health information for consumers on the world wide web: a systematic review.

CONTEXT: The quality of consumer health information on the World Wide Web is an important issue for medicine, but to date no systematic and comprehensive synthesis of the methods and evidence has been performed. OBJECTIVES: To establish a methodological framework on how quality on the Web is evaluated in practice, to determine the heterogeneity of the results and conclusions, and to compare the methodological rigor of these studies, to determine to what extent the conclusions depend on the methodology used, and to suggest future directions for research. DATA SOURCES: We searched MEDLINE and PREMEDLINE (1966 through September 2001), Science Citation Index (1997 through September 2001), Social Sciences Citation Index (1997 through September 2001), Arts and Humanities Citation Index (1997 through September 2001), LISA (1969 through July 2001), CINAHL (1982 through July 2001), PsychINFO (1988 through September 2001), EMBASE (1988 through June 2001), and SIGLE (1980 through June 2001). We also conducted hand searches, general Internet searches, and a personal bibliographic database search. STUDY SELECTION: We included published and unpublished empirical studies in any language in which investigators searched the Web systematically for specific health information, evaluated the quality of Web sites or pages, and reported quantitative results. We screened 7830 citations and retrieved 170 potentially eligible full articles. A total of 79 distinct studies met the inclusion criteria, evaluating 5941 health Web sites and 1329 Web pages, and reporting 408 evaluation results for 86 different quality criteria. DATA EXTRACTION: Two reviewers independently extracted study characteristics, medical domains, search strategies used, methods and criteria of quality assessment, results (percentage of sites or pages rated as inadequate pertaining to a quality criterion), and quality and rigor of study methods and reporting. DATA SYNTHESIS: Most frequently used quality criteria used include accuracy, completeness, readability, design, disclosures, and references provided. Fifty-five studies (70%) concluded that quality is a problem on the Web, 17 (22%) remained neutral, and 7 studies (9%) came to a positive conclusion. Positive studies scored significantly lower in search (P =.02) and evaluation (P =.04) methods. CONCLUSIONS: Due to differences in study methods and rigor, quality criteria, study population, and topic chosen, study results and conclusions on health-related Web sites vary widely. Operational definitions of quality criteria are needed.

Evaluation Studies as Topic↗
PubMed1992

Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE-3 in breast-cancer prognosis.

Taking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE-3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE-3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin-embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to Kaplan-Meier univariate and Cox proportional-hazards multi-variate analysis. Additionally, traditional prognostic variables for breast-cancer prognosis (grade of differentiation, age, tumor size, axillary-lymph-node involvement and estrogen receptors) were subjected to identical analyses. In uni-variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi-variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary-node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni-variate and multi-variate level. A multi-variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary-node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub-populations of patients with infiltrating breast carcinoma with defined risk functions.

Adolescent↗
PubMedDate not supplied

[Awareness of deficits and anosognosia in Alzheimer's disease].

This article reviews studies concerning unawareness of deficits in Alzheimer's disease. Unawareness of the deficits associated with dementia has frequently been reported in clinical descriptions of the later stages of the disease. Consistent with the literature, we shall use the expressions impaired awareness, unawareness of deficits, anosognosia, and lack of insight interchangeably. Anosognosia can be defined as an impaired ability to recognize the presence or appreciate the severity of deficits in sensory, perceptual, motor, affective, or cognitive functioning. Unawareness has been operationally defined in a variety of ways. Unawareness can be measured as the discrepancy between the patient's self-report and the report of a natural caregiver or the clinical rating of a health care professional. The reports generally concern with several domains, most often memory domain. Discrepancy between subjective ratings and neuropsychological performance during clinical assessment has also been used to measure anosognosia. Advantages, limits and equivalence of these different methods are discussed. The impact of family burden has to be considered as a systematic methodological bias if the natural caregiver is implicated in the assessment. The psychometric properties of the clinical assessment have also to be discussed. The psychological nature of the discrepancy between patient's self-report and cognitive performances has to be analyzed and the necessity of ecological protocols, longitudinal assessment is discussed. The major results concerning prevalence, nature of anosognosia and the associated disorders are analyzed. In particular, the notion of heterogeneity of anosognosia and the correlates with depression, severity of dementia and executive dysfunction are developed. Prevalence is largely function of methodological choices and conceptual definition of anosognosia. Three major researches are compared and the contrast between their results (prevalence from 23% to 75% in AD) is analyzed. Particularly, the hypotheses about anosognosia play a great role in the findings. At first time of research, anosognosia was considered as a general symptom and so, studies were centered on the unawareness related to only one cognitive function. But the 90's findings suggest that patients with AD have impaired awareness for some types of deficits (affective or cognitive functions) but can more accurately appraise other deficits. Currently anosognosia cannot be considered as a unitary entity. It may be that patients with AD are unaware of some types of deficits, but are aware of others, and that nature and intensity of their anosognosia may change during the course of the dementia. It has been proposed that depression is more common when disease is mild and awareness of deficits is retained, and that depression becomes less common when disease increases and awareness declines. Depression is conceived as a psychological reaction. However, the correlations between anosognosia level and depression scores reveal either weak relationships or no relationships. Alternative hypothesis is that anosognosia is related to overall dementia severity and to memory impairment. However, correlations of unawareness of deficits, i.e. the difference between self-report and relative's -rating, with a measure of dementia and with patient's performance on objective memory tasks did not reveal strong, consistent relationships between degree of anosognosia and severity of dementia or of memory impairment. On the other hand, the best neuropsychological predictors of impaired insight are Trail Making Test or Wisconsin Card Sorting Test, i.e. tests that have been shown to be sensitive to a frontal lobe dysfunction. SPECT measures of regional cerebral blood flow have been used in the study of anosognosia. The main findings are that unawareness in AD is associated with hypoperfusion of the right dorsolateral frontal lobe. Anosognosia may result from the disruption of broader cognitive process that is subsumed by the frontal lobes. The mechanisms of unawareness are not well known and studies are essentially descriptive works and try to give information about pre-valence or clinical associated disorders of anosognosia. Several authors have proposed that unawareness is part of a defensive mechanism that would protect demented patients from depressive feelings. Other authors have proposed that anosognosia may result from dysfunction in specific brain areas. It is suggested that anosognosia in AD may result from greater impairment of a central executive system, which is a metacognitive structure that is involved in planning, cognitive resource allocation, and set shifting. The main problem with those both major hypotheses is their incapacity to explain the heterogeneous impairment of awareness. Other authors speculate that the impaired insight of Alzheimer's disease has several components, psychological and neuropsychological. This view doesn't seem convincing and new components have to be taken in account in order to propose a theoretical framework about anosognosia in AD. Environmental and dispositional components and an interactional view could be interesting. Those possible directions for future research and solutions concerning methodological and conceptual problems are outlined. In particular, a neuro-psycho-social view of unawareness is introduced.

Aged↗
PubMedDate not supplied

Patient-based measures of illness severity in the Veterans Health Study.

The Veterans Health Study (VHS) was designed to produce patient-based measures of health status suitable for monitoring the health of men served by the Veterans Health Administration. This article summarizes the objectives, conceptual framework, and results of 6 substudies of the VHS that were designed to develop disease-focused measures of illness severity, that is, patient-perceived, clinically significant manifestations of disease processes that are associated with decrements in health-related quality of life. Developmental psychometric studies used cross-sectional survey data from the baseline comprehensive evaluations conducted in the VHS. Patients who screened positive for the 6 study medical conditions in the VHS (osteoarthritis of the knee, n = 511; type 2 diabetes, n = 425; chronic lung disease, n = 352; hypertension, n = 996; chronic low-back pain, n = 574; and alcohol-related disorder, n = 175) were administered structured interview modules that assessed symptoms and complications of these chronic diseases. Psychometric analyses were conducted to identify internally coherent and reliable indices, which were validated with respect to their correlations with measures of health-related quality of life (eg, Short Form-36) and the utilization of health services. We constructed 6 indices of illness severity. The severities of osteoarthritis of the knee and chronic lung disease were defined by brief (12 and 6 items, respectively) assessments of symptoms (eg, knee pain and dyspnea). Since diabetes and hypertension are largely asymptomatic, illness severity for these conditions was assessed by ascertaining complications such as angina and vascular disorders. Alcohol-related disorder, which involves both behavioral symptoms and physical complications, was assessed by separate scales for these 2 dimensions of its severity. Chronic low-back pain required a unique solution. Rather than assessing the intensity of back pain, it is more productive to construct a measure that focuses on manifestations of radiculopathy, that is, whether back pain radiated down the leg to below the knee. The 5 symptoms or complication indices and the assessment of radiculopathy in chronic low-back pain were significantly correlated with Short Form-36 scores and intensity of recent use of health services. The 6 measures may complement measures of health-related quality of life in providing more comprehensive assessments of health status in Veterans Affairs patients.

Chronic Disease↗
PubMed2001

Establishing prognosis and maximizing functional outcomes after spinal cord injury: a review of current and future directions in rehabilitation management.

STUDY DESIGN: Review article. OBJECTIVES: To review the medical literature and provide a framework for predicting neurorecovery and functional outcomes after spinal cord injury based on injury severity. SUMMARY OF BACKGROUND DATA: The ability to accurately predict the magnitude of neurorecovery and expected functional outcomes after spinal cord injury is of great importance. This information is needed to justify medical and rehabilitation interventions to third party payers as well as to begin the process of planning for postdischarge care. Over the past several decades, significant progress has been made in accurately predicting neurorecovery and its impact on functional outcomes. METHODS: Structured review of published reports obtained through MED-LINE search and texts. RESULTS/CONCLUSION: Within 72 hours to 1 month after a spinal cord injury, it is possible to predict with reasonable accuracy the magnitude of expected recovery based on physical examination. The impact of motor level on long-term functional outcomes is also clear and has remained relatively unchanged for several decades. Functional outcomes are likely to improve in upcoming years as novel interventions, such as drugs and functional neuromuscular stimulation, are developed with the goals of limiting secondary injury and restoring neurologic function. New training methods, such as body weight support, that use activity-dependent neuroplasticity will also have a more prominent role.

Humans↗
PubMed2005

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework.

Schizophrenia has long been thought to be clinically heterogeneous. A range of studies suggests that this is due to genetic heterogeneity. Some clinical features, such as negative symptoms, are associated with a greater risk of illness in relatives. Affected sibling pairs are correlated for clinical and course features as well as subforms of illness, and twin studies suggest that this is due to genetic factors. This is further supported by findings that subjects from families linked to some chromosomal regions may differ clinically from those from unlinked families. Moreover, some genes may affect clinical features without altering susceptibility (ie are modifier genes). High-risk genotypes may have quantitative, rather than categorical effects, and may influence milder or subclinical phenotypes. Another recent finding is that nonpsychotic relatives may have personality features that resemble those of their affected relatives. These findings taken together suggest that there may be several classes of gene action in schizophrenia: some genes may influence susceptibility only, others may influence clinical features only, and still others may have a mixed effect. Furthermore, subsets of these classes may affect personality and other traits in nonpsychotic relatives. Understanding these classes of gene action may help guide the design of linkage and association studies that have increased power. We describe five classes of genes and their predictions of the outcomes of family, twin, and several types of linkage studies. We go on to explore how these predictions can in turn be used to aid in the design of linkage studies.

Genetic Linkage↗
PubMed1999

Point and interval estimates of marker location in radiation hybrid mapping.

Radiation hybrid (RH) mapping is a powerful method for ordering loci on chromosomes and for estimating the distances between them. RH mapping is currently used to construct both framework maps, in which all markers are ordered with high confidence (e.g., 1,000:1 relative maximum likelihood), and comprehensive maps, which include markers with less-confident placement. To deal with uncertainty in the order and location of markers, marker positions may be estimated conditional on the most likely marker order, plausible intervals for nonframework markers may be indicated on a framework map, or bins of markers may be constructed. We propose a statistical method for estimating marker position that combines information from all plausible marker orders, gives a measure of uncertainty in location for each marker, and provides an alternative to the current practice of binning. Assuming that the prior distribution for the retention probabilities is uniform and that the marker loci are distributed independently and uniformly on an interval of specified length, we calculate the posterior distribution of marker position for each marker. The median or mean of this distribution provides a point estimate of marker location. An interval estimate of marker location may be constructed either by using the 100(alpha/2) and 100(1-alpha)/2 percentiles of the distribution to form a 100(1-alpha) % posterior credible interval or by calculating the shortest 100(1-alpha) % posterior credible interval. These point and interval estimates take into account ordering uncertainty and do not depend on the assumption of a particular marker order. We evaluate the performance of the estimates on the basis of results from simulated data and illustrate the method with two examples.

Bayes Theorem↗
PubMed1999

Community-based empowerment programme for families with a brain injured survivor: an outcome study.

Rehabilitation of brain injured persons has been one of the challenges of the modern health care team. Brain injured persons' problems are termed complex and multiple, and may persist long after the acute management stage. Families caring for their brain-injured members are, however, ill prepared to face this long-term rehabilitation process. A previous study of an empowerment framework applicable among these Hong Kong Chinese families resulted in the development of a 52-item empowerment questionnaire with four interpretable factors (efficacy, knowledge, support and aspiration). This can also serve as a valid and reliable outcome measure of their empowerment efforts. As a follow-up of this development, an 8-week community-based empowerment programme was thus designed and implemented for a total of 50 family members in six repeated groups. Outcome indicators including empowerment questionnaire, psychological well-being, self-efficacy, subjective experience of the burdens in care-giving, and support systems were used to monitor changes in empowerment status during the periods of pre- and post-programme, and during the 3 month follow-up. The programmes were found to be effective in empowering family members in the four postulated empowering dimensions, and improving all other outcome measures. The follow-up studies reflect stability in empowerment, though there were no further improvement. From regression analysis, it was suggested that, for optimum empowerment to take place, important predictors included careers' education levels, age ranges and work status.

Adaptation, Psychological↗
PubMed2001

Construction of a high-resolution RH map of the human 2q35 region on TNG panel and comparison with a physical map of the porcine homologous region 15q25.

This article describes the construction of a high-resolution radiation hybrid map of Hsap 2q35 by using the TNG RH panel generated by irradiation with 50,000 rads. We were able to build a framework map of 1300 cR(50,000) including 34 markers ordered with odds higher than 1000:1. The comprehensive map includes 77 loci and describes a region of 3 Mb around the SLC11A1 gene. Because of the very small size of the fragments retained and a reduced retention frequency, it was difficult to build a high-resolution multi-point map of this region by using the TNG RH panel. Nevertheless, this study confirmed the very high potential of this RH panel for constructing a human, high-resolution physical map (2.3 kb/cR(50,000)). Moreover, human ESTs from Hsap 2q35 were hybridized with porcine BAC contigs to establish a porcine transcript map of the homologous region Sscr 15q25 (greater than 2.5 Mb). We identified 17 new genes in this porcine chromosomal region. We were able to compare the location of 26 genes mapped in both species. The gene order was similar except for two possible minor discrepancies in the Desmin sub-region, suggesting the existence of a porcine micro-region between TNP1 and IL8RB with an unknown origin.

Animals↗
PubMed2005

The high prevalence of bipolar spectrum disorders in young adults with recurrent depression: toward an innovative diagnostic framework.

BACKGROUND: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. METHODS: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off > or =8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. RESULTS: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. LIMITATIONS: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi's BSD construct. CONCLUSIONS: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile.

Adult↗
PubMed2026

Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis.

Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single-cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single-cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC-related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand-receptor expression patterns and ligand-associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single-cell-derived inflammatory and remodeling signatures were represented at the tissue-transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine-response, and stress-response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll-like receptor signaling, and inflammasome-associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+ synthetic VSMCs, KRT7+ VSMC-like cells, interferon-responsive VSMCs, pericyte-like mural cells, and osteogenic/modulated VSMCs. Pseudotime analysis showed a broad contractile-to-osteogenic/modulated transcriptional continuum accompanied by increased expression of remodeling-associated genes and selected inflammatory or remodeling-associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand-receptor and ligand-associated target gene expression patterns involving SPP1-CD44, TNF-TNFRSF1A, IL1B-IL1R1/IL1RAP, MIF-ACKR3, PDGFB-PDGFRB, and FN1-SDC1/ITGB1. In GSE28829, inflammatory macrophage-, osteogenic/modulated VSMC-, candidate ligand-receptor expression-, SPP1-CD44 candidate axis-, and NicheNet-prioritized target program-related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrative transcriptomic analysis identified a highly inflammatory macrophage state and a VSMC remodeling continuum in human atherosclerotic plaques. Candidate ligand-receptor and ligand-associated target gene expression patterns linked inflammatory macrophage activation with osteogenic/modulated VSMC remodeling at the computational level. External bulk data further showed coordinated enrichment of inflammatory and remodeling signatures in advanced plaques. These findings provide a descriptive and hypothesis-generating transcriptomic framework for understanding inflammatory macrophage activation and VSMC remodeling in human atherosclerosis.

atherosclerosis↗
PubMed2005

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Animals↗
PubMed2003

Depression after traumatic brain injury: a National Institute on Disability and Rehabilitation Research Model Systems multicenter investigation.

OBJECTIVE: To identify the frequency and manifestations of depression after traumatic brain injury (TBI) and the factors that contribute to developing this mood disorder. DESIGN: A prospective, nationwide, multicenter study; 17 centers supplied data from medical records and patient responses on a standardized criterion instrument. SETTING: Traumatic Brain Injury Model Systems programs. PARTICIPANTS: A demographically diverse sample of 666 outpatients with TBI was evaluated 10 to 126 months after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Depressive symptoms were characterized with the Neurobehavioral Functioning Inventory by using the Diagnostic and Statistical Manual of Mental Disorders (4th ed; DSM-IV) diagnostic framework. Analysis of variance and Pearson correlations were used to identify factors that were significantly related to depression. RESULTS: Fatigue (29%), distractibility (28%), anger or irritability (28%), and rumination (25%) were the most commonly cited depressive symptoms in the sample. Twenty-seven percent of patients with TBI met the prerequisite number (>/=5) of criterion A symptoms for a DSM-IV diagnosis of major depressive disorder. Feeling hopeless, feeling worthless, and difficulty enjoying activities were the 3 symptoms that most differentiated depressed from nondepressed patients. Patients who were unemployed at the time of injury and who were impoverished were significantly more likely to report DSM-IV criterion A symptoms than patients who were employed, were students, or were retired due to age. Time after injury, injury severity, and postinjury marital status were not significantly related to depression. CONCLUSIONS: Patients with TBI are at great risk for developing depressive symptoms. Findings provide empirical support for the inclusion of depression evaluation and treatment protocols in brain injury programs. Unemployment and poverty may be substantial risk factors for the development of depressive symptoms. Future research should develop biopsychosocial predictive models to identify high-risk patients and examine the efficacy of treatment interventions.

Adolescent↗
PubMed1997

A radiation hybrid map of human chromosome 5 with integration of cytogenetic, genetic, and transcript maps.

One of the major goals of the human genome project is to establish a physical map of each human chromosome with a density of sequence-tagged site (STS) markers exceeding one every 100 kb. We report here the generation of a human chromosome 5-specific radiation hybrid (RH) map that includes 556 markers. Of these markers, 132 loci are ordered with a maximum likelihood ratio of >1000:1 compared with the next most likely order. An additional 113 loci were ordered relative to these backbone markers with a maximum likelihood ratio of >10:1 but <1000:1. Together, these 245 loci form an ordered framework map for the chromosome. Using this framework, >300 more markers were localized based on two-point analysis with the ordered set. On average, there are 50 markers in common with the RH map presented here and other chromosome 5 maps included in the current whole genome cytogenetic, genetic, and physical maps. The accuracy of all the maps is evident in that there are no more than two discrepancies between any one of them and these data. All of the maps encompassing chromosome 5 complement each other providing excellent STS coverage with >2200 loci combined. The chromosome 5-specific RH map contains 20% of these independent loci. In addition, our RH map contains STSs derived from clones suitable for fluorescent in situ hybridization, allowing alignment to the cytogenetic map. Together, these maps will assist in the assembly of sequence-ready contigs and will aid in the identification of disease loci on chromosome 5 by positional cloning and positional candidate approaches.

Centromere↗
PubMedDate not supplied

[Characteristics of pregnant women, labor, and the newborn at the Skopje Clinic from 1978 to 1979].

An analysis was made of the first computer data received from the IFRP (International Fertility Research Program) within the framework of the International Study "Maternity Record" -- "Maternity Monitoring Care'. The main findings are the following: The women who were confined at the Skopje University Hospital during 1978--1979 were young, in their twenties. Women over thirty were confined very rarely. Most of the women surveyed had about 12 years of education. Pregnant women had artificial abortions very rarely (1:5.7 in favor of terminating pregnancy). Preventive work on contraception should include women at the time of delivery. Pregnant women in Skopje come to the Consulting Centers for a check-up mostly five times. The higher the parity, the less frequent the visits. More than half of pregnant women during the antenatal period had no complaints. Younger pregnant women had fewer difficulties and complications. The values of haemoglobin under 10 g% were very often in primiparas and over 12 g% in multiparas. The birthweight of women smoker's babies proved lower than that of women non-smokers' babies. In two thirds of women the delivery was induced by drugs and amniotomy. The delivery mostly lasted between 7--12 h, regardless of parity. Prolonged deliveries were the more frequent the younger the women. Primiparas gave birth to babies with a lower birthweight than multiparas. Almost all women (92.4%) were previously using no contraceptive devices. The main method of protection was coitus interruptus.

Adult↗
PubMed2005

Reasonable suspicion: a study of Pennsylvania pediatricians regarding child abuse.

OBJECTIVE: It has long been assumed that mandated reporting statutes regarding child abuse are self-explanatory and that broad consensus exists as to the meaning and proper application of reasonable suspicion. However, no systematic investigation has examined how mandated reporters interpret and apply the concept of reasonable suspicion. The purpose of this study was to identify Pennsylvania pediatricians' understanding and interpretation of reasonable suspicion in the context of mandated reporting of suspected child abuse. Methodology. An anonymous survey was sent (Spring 2004) to all members of the Pennsylvania chapter of the American Academy of Pediatrics (n = 2051). Participants were given several operational frameworks to elicit their understanding of the concept of reasonable suspicion, 2 of which are reported here. Respondents were asked to imagine that they had examined a child for an injury that may have been caused by abuse and that they had gathered as much information as they felt was possible. They then were asked to quantify (in 2 different ways) the degree of likelihood needed for suspicion of child abuse to rise to the level of reasonable suspicion. The physicians were asked to identify (using a differential-diagnosis framework) how high on a rank-order list "abuse" would have to be for it to rise to the level of reasonable suspicion (ie, first on the list, second, third, and so on, down to tenth). The second framework, estimated probability, used a visual analog scale of 0% to 100% to determine how likely suspected abuse would have to be for physicians for them to feel that they had reasonable suspicion. That is, would they need to feel that there was a 99% likelihood that abuse occurred before they felt that they had reasonable suspicion, a 1% likelihood, or something in between? In addition to standard demographic features, respondents were queried regarding their education on child abuse, education on reasonable suspicion, frequency of reporting child abuse, and (self-reported) expertise regarding child abuse. The main outcome measures were physician responses on the 2 scales for interpreting reasonable suspicion. RESULTS: Pediatricians (n = 1249) completed the survey (61% response rate). Their mean age was 43 years; 55% were female; and 78% were white. Seventy-six percent were board certified, and 65% reported being in primary care. There were no remarkable differences in responses based on age, gender, expertise with child abuse, frequency of reporting child abuse, or practice type. The responses of pediatric residents were indistinguishable from experienced physicians, and the responses of primary care pediatricians were no different from pediatric subspecialists. Wide variation was found in the thresholds that pediatricians set for what constituted reasonable suspicion. On the differential-diagnosis scale (DDS), 12% of pediatricians responded that abuse would have to rank first or second on the DDS before the possibility rose to the level of reasonable suspicion, 41% indicated a rank of third or fourth, and 47% reported that a rank anywhere from fifth to as low as tenth still qualified as reasonable suspicion. On the estimated-probability scale (EPS), 35% of pediatricians responded that for reasonable suspicion to exist, the probability of abuse needed to be 10% to 35%. By contrast, 25% of respondents identified a 40% to 50% probability, 25% stipulated a 60% to 70% probability, and 15% required a probability of >or=75%. In comparing individual responses for the 2 scales (ie, paired comparisons between each pediatrician's DDS ranking and the estimated probability he or she identified), 85% were found to be internally inconsistent. To be logically consistent, any score >or=50% on the EPS would need to correspond to a DDS ranking of 1; an EPS score of >or=34% would need to correspond with a DDS ranking no lower than 2; an EPS score of >or=25% no lower than a DDS ranking of 3; and so on. What we found, however, was that pediatricians commonly indicated that reasonable suspicion required a 50% to 60% probability that abuse occurred, but at the same time, they responded that child abuse could rank as low as fourth or fifth on the DDS and still qualify as reasonable suspicion. CONCLUSIONS: The majority of states use the term "suspicion" in their mandated reporting statutes, and according to legal experts, "reasonable suspicion" represents an accurate generalization of most mandated reporting thresholds. Our data show significant variability in how pediatricians interpret reasonable suspicion, with a range of responses so broad as to question the assumption that the threshold for mandated reporting is understood, interpreted, or applied in a coherent and consistent manner. If the variability described here proves generalizable, it will require rethinking what society can expect from mandated reporters and what sort of training will be necessary to warrant those expectations.

Adult↗
PubMed2006

Marlboro UltraSmooth: a potentially reduced exposure cigarette?

AIM: To compare relative toxic emissions scores (RTE) of the carbon filter cigarette Marlboro UltraSmooth (MUS), against regular Marlboro, Holiday, and British Columbian brands. METHOD: MUS cigarettes were purchased in Tampa, Florida; Marlboro regular and Holiday were purchased in Auckland, New Zealand, and all emissions tested by Labstat International Inc, Kitchener, Ontario under Health Canada Intensive (HCI) machine-smoking conditions (55 ml puff per 30 seconds, filter ventilation holes blocked) against: (1) previous same brand emissions tested under ISO (International Organization for Standardization) conditions; (2) ISO and HCI average emissions for 16 regular brands sold in British Columbia (BC), the reference standard. Toxicants, selected by toxicological risk assessment, enabled estimation of an RTE per brand, and RTE per mg of nicotine. RESULTS: The BC standard for RTE in both ISO and HCI test modes, including metals and nitrosamines, was set at 100. Hereafter excluding them, RTE in ISO mode for BC was 97, MUS 4, Marlboro 102, and Holiday regular 99; and in HCI test mode BC was 97, MUS 42, Marlboro regular 107, and Holiday 95. From ISO to HCI, MUS total puff volume increased 50%, from 252 ml to 380 ml; nicotine yield increased 2.6 fold. Normalising for nicotine (RTE per mg nicotine), in ISO test mode, the BC standard was 97, MUS 10, Marlboro regular 124, and Holiday regular 107. In HCI mode, however, MUS/nicotine at 104 exceeded the average BC standard of 97; Marlboro regular was 137, and Holiday regular 97; MUS ranked sixth highest among 18 regular brands. MUS contained 103 mg of carbon in its 304 mg filter, which was 55% ventilated. CONCLUSION: The combined acetate-carbon filter of MUS performed best at low smoke volumes on ISO testing. Under more smoker-realistic intensive machine testing, and correcting for relative nicotine concentration and compensatory smoking, MUS increased the RTE, for all toxicants combined, for carcinogens, and for cardiovascular toxicants, compared with most regular brands. MUS was not a potentially reduced-exposure product (PREP) under smoker-realistic test conditions, and thus would not be expected to reduce overall harm. It is unrealistic to expect that even major design changes, as seen in MUS, or a regulatory framework to enforce such changes, could reduce cigarette smoking mortality risks to acceptable levels.

Environmental Exposure↗
PubMed2005

Quantitative trait locus study design from an information perspective.

We examine the efficiency of different genotyping and phenotyping strategies in inbred line crosses from an information perspective. This provides a mathematical framework for the statistical aspects of QTL experimental design, while guiding our intuition. Our central result is a simple formula that quantifies the fraction of missing information of any genotyping strategy in a backcross. It includes the special case of selectively genotyping only the phenotypic extreme individuals. The formula is a function of the square of the phenotype and the uncertainty in our knowledge of the genotypes at a locus. This result is used to answer a variety of questions. First, we examine the cost-information trade-off varying the density of markers and the proportion of extreme phenotypic individuals genotyped. Then we evaluate the information content of selective phenotyping designs and the impact of measurement error in phenotyping. A simple formula quantifies the information content of any combined phenotyping and genotyping design. We extend our results to cover multigenotype crosses, such as the F(2) intercross, and multiple QTL models. We find that when the QTL effect is small, any contrast in a multigenotype cross benefits from selective genotyping in the same manner as in a backcross. The benefit remains in the presence of a second unlinked QTL with small effect (explaining <20% of the variance), but diminishes if the second QTL has a large effect. Software for performing power calculations for backcross and F(2) intercross incorporating selective genotyping and marker spacing is available from http://www.biostat.ucsf.edu/sen.

Animals↗