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Choosing Wisely began at a time when a polarized national debate on healthcare reform stymied effective conversation on effective and efficient resource use. The ABIM Foundation sought to change attitudes and culture and promote the idea that removing waste is an integral component of providing high quality care by using an approach of constructive engagement to persuade specialty societies to identify five wasteful tests or treatments within their field., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several targeted therapies have been approved for treatment of solid tumors. Identification of gene mutations that indicate response to these therapies is rapidly progressing. A 34-gene next-generation sequencing (NGS) panel, developed and validated by us, was evaluated to detect additional mutations in community-based cancer specimens initially sent to our reference laboratory for routine molecular testing., Methods: Consecutive de-identified clinical specimens (n = 121) from melanoma cases (n = 31), lung cancer cases (n = 27), colorectal cancer cases (n = 33), and breast cancer cases (n = 30) were profiled by NGS, and the results were compared with routine molecular testing., Results: Upon initial mutation testing, 20 % (24/121) were positive. NGS detected ≥1 additional mutation not identified by routine testing in 74 % of specimens (90/121). Of the specimens with additional mutations, 16 harbored mutations in National Comprehensive Cancer Network guideline genes. These various additional mutations were in gene regions not routinely covered, in genes not routinely tested, and/or present at low allele frequencies. Moreover, NGS yielded no false negatives. Overall, NGS detected mutations in 59 % of the genes (20/34) included in the panel, 75 % of which (15/20) were detected in multiple tumor types. Mutations in TP53 were found in 51 % of tumors tested (62/121). Mutations in at least one other (non-TP53) gene present in the panel were detected in 64 % of cases (77/121)., Conclusion: This assay provides improved breadth and sensitivity for profiling clinically relevant genes in these prevalent solid tumor types.

Three-dimensional (3D) multicellular spheroids of human adipose tissue-derived stem cells (hASCs) are an attractive system for basic science studies and tissue engineering applications, as they can resemble cellular condensations present in developmental and healing processes. The purpose of this study was to engineer a hydrogel-based microwell platform by capitalizing on the differential swelling behavior of micropatterned dual-crosslinked oxidized, methacrylated alginate (OMA)/multi-arm polyethylene glycol (PEG) hydrogels for rapid formation of uniform multicellular hASC spheroids with controllable size and evaluation of the capacity of the system to be used to drive osteogenic differentiation of the spheroids. By changing the micropattern size, the size of the hydrogel microwells was easily controllable. Microwell-seeded hASCs generated spheroids of relatively uniform size and high cell viability. hASC spheroids exhibited rapid mineralization in osteogenic media, which was faster than that of conventional two-dimensionally cultured hASCs. This new hydrogel microwell system has great potential for controlled multicellular spheroid formation and defined signal presentation from the hydrogel material to the cell aggregates to regulate tissue formation.

Experimental testing of orthopaedic implants requires simplifications concerning load application and activities being analyzed. This computational study investigated how these simplifications affect micromotions at the bone-implant interface of an uncemented femoral knee implant. As a basis, validated in vivo loads of the stance phase of gait and a deep knee bend were adopted. Eventually, three configurations were considered: (i) simulation of the complete loading cycle; (ii) inclusion of only tibiofemoral loads (ignoring patellofemoral loads); and (iii) applying only a single peak tibiofemoral force. For all loading conditions the largest micromotions found at the proximal anterior flange. Without the patellofemoral force, peak micromotions increased 6% and 22% for gait and deep knee bend, respectively. By applying a single peak tibiofemoral force micromotions were overestimated. However, the peak micromotions corresponded to the maximum tibiofemoral force, and strong micromotion correlations were found between a complete loading cycle and a single peak load (R(2)  = 0.73 and R(2)  = 0.89 for gait and deep knee bend, respectively). Deep knee bend resulted in larger micromotions than gait. Our study suggests that a simplified peak force can be used to assess the stability of cementless femoral components. For more robust testing, implants should be subjected to different loading modes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:812-819, 2016., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Fetoscopic laser surgery aims to treat Twin-to-Twin Transfusion Syndrome with a single procedure. In rare cases, missed or recanalized anastomoses lead to recurrent disease, either postlaser Twin Anemia Polycythemia Sequence (TAPS) or recurrent Twin-to-Twin Transfusion Syndrome (TTTS). Repeat laser surgery is one possible treatment., Objectives: To describe our diagnostic and treatment criteria for recurrent disease along with technical strategies to perform repeat laser. We explore the clinical implications of repeat laser surgery by comparing characteristics and outcomes to patients matched for TTTS disease severity that was successfully treated by a single laser surgery., Study Design: We performed a single-center, matched-case, retrospective analysis. Patients who underwent repeat laser surgery for disease recurrence are described in detail and were matched in a ratio of 1:3 to patients whose TTTS was treated with a single fetoscopic laser surgery. Patients were matched for disease stage, co-existing fetal growth restriction, and gestational age (GA) epoch at first laser (<18, 18-23.9, and ≥24). Gestational age at delivery was the primary outcome measure. Demographics, pregnancy characteristics, procedure details, complications, obstetric, and twin survival outcomes were compared. Continuous data were analyzed using Student's t or Wilcoxon Rank-Sum test and categorical data were analyzed using Chi squared or Fisher's exact test., Results: Sixteen (4.8%) of 334 patients met our criteria for recurrent disease after Solomon laser for TTTS: 12 had postlaser TAPS, three had recurrent TTTS, and two had both postlaser TAPS and recurrent TTTS. Repeat laser was performed in 11 (69%) patients. Techniques for repeat laser included carbon dioxide insufflation (2/11), amnioexchange (2/11), contralateral trochar entry (8/11), intentional septostomy (4/11), and entry into the opposite sac (2/11). There was no difference in median gestational age at delivery (31 vs 32.5 weeks, p  = 0.228), double birth survival (72.7% vs 87.9%, p  = 0.34), or overall perinatal survival (86% vs 91%, p  = 0.89) between patients who underwent repeat laser and matched controls., Conclusions: We suggest a standardized approach to diagnosis of postlaser TAPS and recurrent TTTS and technical considerations for performing repeat laser. In patients eligible for repeat laser surgery, it is possible to achieve acceptable outcomes that are comparable to outcomes after single laser in patients matched for TTTS disease severity. These findings should be corroborated in a larger multicenter study, but may be useful to help patient counseling and management when repeat laser surgery is considered for recurrent disease.

We demonstrate an approach to rapidly characterize living suspension cells in 4 dimensions while they are immobilized and manipulated within optical traps. A single, high numerical aperture objective lens is used to separate the imaging plane from the trapping plane. This facilitates full control over the position and orientation of multiple trapped cells using a spatial light modulator, including directed motion and object rotation, while also allowing rapid 4D imaging. This system is particularly useful in the handling and investigation of the behavior of non-adherent immune cells. We demonstrate these capabilities by imaging and manipulating living, fluorescently stained Jurkat T cells., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Much attention has been paid to the inappropriate underuse of tests and treatments but until recently little attention has focused on the overuse that does not add value for patients and may even cause harm. Choosing Wisely is a campaign to engage physicians and patients in conversations about unnecessary tests, treatments and procedures. The campaign began in the United States in 2012, in Canada in 2014 and now many countries around the world are adapting the campaign and implementing it. This article describes the present status of Choosing Wisely programs in 12 countries. It articulates key elements, a set of five principles, and describes the challenges countries face in the early phases of Choosing Wisely. These countries plan to continue collaboration including developing metrics to measure overuse., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We investigated the effect of surface morphology on the mechanical performance of uncemented femoral knee prosthesis. Eighteen implants were implanted on nine paired femurs and then pushed-off (left legs: a novel surface morphology; right legs: Porocoat as baseline). Bone mineral density (BMD) and anteroposterior dimension were not significantly different between groups. The insertion force was not significantly different, however, the loosening force was significantly higher in the novel group (P=0.007). BMD had a direct relationship with the insertion and loosening force (P<0.001). The effect of surface morphology on implant alignment was very small. We conclude that the surface properties create a higher frictional resistance, thereby providing a better inherent stability of implants featuring the novel surface morphology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Initial fixation of press-fit implants depends on interference fit, surface morphology, and bone material properties. To understand the biomechanical effect of each factor and their interactions, the pull-out strength of seven types of CoCrMo tapered implants, with four different interference fits, three different surface morphologies (low, medium and high roughness), and at two time points (0 and 30 min) were tested in trabecular bone with varying density. The effect of interference fit on pull-out strength depended on the surface morphology and time. In contrast with our expectations, samples with a higher roughness had a lower pull-out strength. We found a similar magnitude of bone damage for the different surface morphologies, but the type of damage was different, with bone compaction versus bone abrasion for low and high frictional surfaces, respectively. This explains a reduced sensitivity of fixation strength to bone mineral density in the latter group. In addition, a reduction in fixation strength after a waiting period only occurred for the low frictional specimens. Our study demonstrates that it is essential to evaluate the interplay between different factors and emphasizes the importance of testing in natural bone in order to optimize the initial stability of press-fit implants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community., Methods: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire., Results/conclusions: The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization., (© 2015 S. Karger AG, Basel.)

Wise management of health care resources is a core tenet of medical professionalism. To support physicians in fulfilling this responsibility and to engage patients in discussions about unnecessary care, tests, and procedures, in April 2012 the American Board of Internal Medicine Foundation, Consumer Reports, and nine medical specialty societies launched the Choosing Wisely campaign. The authors describe the rationale for and history of the campaign, its structure and approach in terms of engaging both physicians and patients, lessons learned, and future steps.In developing the Choosing Wisely campaign, the specialty societies each developed lists of five tests and procedures that physicians and patients should question. Over 50 specialty societies have developed more than 250 evidence-based recommendations, some of which Consumer Reports has "translated" into consumer-friendly language and helped disseminate to tens of millions of consumers. A number of delivery systems, specialty societies, state medical societies, and regional health collaboratives are also advancing the campaign's recommendations. The campaign's success lies in its unique focus on professional values and patient-physician conversations to reduce unnecessary care. Measurement and evaluation of the campaign's impact on attitudinal and behavioral change is needed.

Study Objective: In rural settings, long distances and transport times pose a challenge for achieving early reperfusion goals in patients with ST-elevation myocardial infarction (STEMI). This study investigated the association between the method of pre-hospital 12-lead ECG transmission (radio transmission vs. cellular phone transmission) and the success of transmission and legibility of 12-lead ECGs in a rural setting., Methods: Observational study of pre-hospital 12-lead ECG transmission to the emergency department (ED) in a predominantly rural area. Success of transmission and the legibility of the 12-lead ECG were analyzed to identify barriers to 12-lead ECG transmission and reasons for failed transmission., Results: Emergency medical services performed ECGs on 1140 patients, 917 of which they attempted to transmit, including 43 cases requiring emergent catheterization. Twelve-lead ECG transmission was successful in 236 (70%) of 337 radio attempts and 441 (76%) of 580 cellular attempts (difference 6.0%, 95% CI 1.1-12.1). Legibility increased from 164 (49%) of 337 radio attempts to 389 (67%) of 580 cellular attempts (difference 18.4%, 95% CI 11.8-24.9)., Conclusion: The success of transmission and legibility of 12-lead ECGs was significantly higher with cellular technology by emergency medical service agencies in comparison to radio transmission. In rural settings with lengthy transport times, utilization of cellular technology for transmission of pre-hospital 12-lead ECGs may improve door-to-balloon times for STEMI patients., (© 2013.)

The aim of this study was to investigate the accuracy of imprint cytology (IC) of breast core biopsy under ultrasound guidance and to assess the value of a rapid on-site preliminary diagnosis of breast lesions. A total of 437 breast core needle biopsies under ultrasound guidance with touch imprint cytology, histology, and final diagnosis were reviewed. These cases were collected from archived files at our institution. Of 437 core biopsies, IC classified 241 (55%) as benign; 22 (5%) as probably benign; 28 (6%) as probably malignant; 107 (25%) as malignant; and 39 (9%) as inadequate for IC diagnosis. Histological classifications for the 437 cases were: 285 (65%) benign; 132 (30%) malignant; 16 (4%) atypical hyperplasia; and 4 (1%) inadequate specimen. The overall sensitivity and specificity indices of IC were 95% and 96%, respectively, for benign and probably benign lesions vs malignant and probably malignant breast lesions. The overall positive and negative predictive values were 91% and 97%, respectively. The overall accuracy was 95% (379 of 398 cases, excluding specimens inadequate for IC diagnosis). IC of ultrasound-guided core needle biopsy provides a rapid and reliable preliminary diagnosis for breast lesions; it also serves as a means to verify the adequacy of biopsy specimens and to optimize the biopsy procedure. Use of IC may reduce anxiety in patients with benign lesions and expedite the diagnosis and assessment of treatment options in patients with breast cancer.

Papillary thyroid carcinoma with metastasis to the frontal skull is extremely rare. We report a case of unsuspected papillary thyroid carcinoma with frontal skull metastasis. The patient was a 62-year-old African American woman with presentation of a 4-cm firm, painless, immobile, ill-defined mass at the right forehead. Ultrasound and computer tonography detected a hypervascular and osteolytic tumor involving the skull and overlying skin. Fine-needle aspiration was performed followed by surgical biopsy. Cytologic examination revealed the presence of hypercellular and bloody material. The neoplasm showed glandular features and was composed of clusters of round to oval cells with pinkish squamoid cytoplasm, oval nuclei and inconspicuous nucleoli on smears and sections of cell block. With immunocytochemical stain, the neoplastic cells were positive for pancytokeratin and vimentin and focally positive for EMA, while they were negative for S100, HMB45, Melan-A, CD34, GFAP, CD10, LCA, RCC and CD138. The diagnosis was a metastatic carcinoma. Clinical follow up with surgical biopsy was recommended. Surgical biopsy demonstrated histological and cytological features of papillary thyroid carcinoma including prominent papillae, nuclear overlapping, grooves, and intranuclear pseudoinclusions. Thus, a diagnosis of metastatic papillary thyroid carcinoma was rendered. Though skull metastasis of thyroid carcinoma is rare, it should be considered in the differential diagnosis when a skull mass lesion is encountered., (2009 Wiley-Liss, Inc.)

Sensation and perception, as well as motor functions, have played an important role in the history of psychology. Although tests of these abilities are sometimes included in neuropsychological assessments, comparisons of intraindividual performances on the two sides of the body (as a basis for drawing conclusions and comparisons about the functional status of the two cerebral hemispheres) are in many instances neglected or considered only casually. This study, utilizing several motor and sensory-perceptual tests, compared intraindividual differences on the two sides of the body in a group of controls and a group of persons with brain damage. The results indicated that the sensory-perceptual tests were particularly effective in differentiating the groups. More than 60% of the group with brain damage had greater differences on the two sides of the body than did any of the controls. These findings suggest that a substantial proportion of persons with cerebral disease or damage may be subject to unequivocal identification using sensory-perceptual tests that take only about 20 minutes to administer. These tests may serve a valuable role as an adjunct to comprehensive neuropsychological evaluation and should be further evaluated in this respect.

This study was designed to use a short, two-phase testing procedure to predict the outcome of a comprehensive neuropsychological examination among young children (aged 5-8 years). Phase 1, requiring less than 10 minutes to administer, predicted Phase 2 results and results of comprehensive testing with acceptable accuracy. Phase 2 testing evaluated both lower-level (sensory-motor) and higher-level functions, required about 45 minutes to administer, and also closely predicted the outcome of comprehensive testing. Cutoff scores for individual tests, areas of function, and the total score for preliminary testing were determined, and accuracy rates were identified. The results suggest that preliminary testing, as described in this article, may serve to identify young children who need a comprehensive neuropsychological examination.

Neuropsychological tests that produce continuous distributions routinely show some degree of overlap between groups with and without brain damage, and there is an inevitable degree of uncertainty in group differentiation when using statistical inferential methods. Recognizing these circumstances, Pliskin, Ramati, and Sweeney (2007) recently stated that neuropsychological testing alone does not address the underlying basis (or brain damage) for cognitive changes that may be inferred from test results. The present study proposed that brain-based specific deficits, evaluated on a "present" or "absent" basis, might prove to be a valuable resource in supplementing interpretation of tests based on continuous distributions by providing, in many instances, unequivocal evidence of brain damage. Comparisons of controls with a group of brain-damaged persons, as reported in this study, strongly supported this proposal.

The aim of this study was to develop a short screening battery that would predict whether older children would show significant impairment on comprehensive neuropsychological testing. The screening battery was subdivided into two phases. Phase 1 was intended as a broad catchment effort; Phase 2 was designed to be a more detailed and selective procedure. Administration of the full set of screening tests requires about 45 minutes. Their predictive validity was assessed using the Neuropsychological Deficit Scale (NDS), which summarizes results in the entire Halstead-Reitan Neuropsychological Test Battery for Older Children. Cutoff scores and guidelines for interpretation of the screening tests were developed, and the results were substantially correct in identifying children who performed normally versus children who were impaired on the testing and therefore required comprehensive testing to evaluate their neuropsychological status and deficits.

The aim of this study was to develop brief neuropsychological testing procedures that would identify adults (aged 15 and older) who need comprehensive neuropsychological evaluation. The tests used for screening were selected to (1) initially provide a broad catchment procedure followed by (2) a more diversified basis for prediction. The total time required to administer the screening measures is about 45 minutes. The criterion for the need for comprehensive testing was based on the General Neuropsychological Deficit Scale (GNDS), which summarizes 42 variables derived from the complete Halstead-Reitan Battery. The results indicated that the brief testing battery permitted accurate identification of persons who showed neuropsychological impairment based on comprehensive testing. Cutoff points were determined and guidelines were provided for use of the brief testing results.

The clinical course of Crohn's disease (CD) is characterized by unpredictable phases of disease activity and quiescence. The majority of CD patients experience mild to moderate disease or are in clinical remission over significant periods during the course of their disease. These patients can be treated conservatively with 5-aminosalicylates or budesonide depending on the disease location. Those patients with more severe forms of the disease who require corticosteroids should be treated more aggressively with early introduction of immunomodulator and/or biologic therapy, which may help to prevent the complications associated with CD. It has been suggested that therapies directed at mucosal healing may favorably modify the natural history of CD. As newer, more effective medications become available and new therapeutic approaches are introduced (top-down therapy), mucosal healing, and not solely clinical remission, may well become the preferred treatment objective.

There is a well-recognized association between dysontogenetic tumors of the spinal cord (including teratomas and enterogenous cysts) and dysraphic congenital spinal malformations. The authors present a case of an adult with an intramedullary mature teratoma (IMMT) at the level of C1-2 of the cord associated with dysraphic congenital spinal malformations. Intramedullary mature teratomas of the cervical region of the spinal cord are very rare in adults; only four such lesions have been reported, two of which involved upper cervical segments. Despite the potentially critical location of the tumor, monitored microsurgery resulted in complete removal of the tumor with an intact surrounding capsule, associated fibrous tract, and ellipse of skin with a central dimple. There was an excellent postoperative neurological outcome. The clinical features, imaging studies, treatment options, postoperative outcome, and plausible pathological correlations of IMMTs are discussed.

Boerhaave's syndrome is the spontaneous transmural rupture of the esophagus. A high degree of clinical suspicion is a prerequisite for its prompt diagnosis, and early therapeutic intervention reduces its associated morbidity and mortality. Factors that influence the outcome are location and extent of perforation and the timing of medical or surgical treatment. Boerhaave's syndrome is the most lethal perforation of the gastrointestinal tract. Delay in intervention relates directly to increased mortality. Despite advances in surgical techniques and endoscopic therapies, this disorder still has high morbidity and mortality rates. The outcome of patients with this disorder is dependent upon the prompt and accurate diagnosis. Initial stabilization of the patient with intravenous fluids and antibiotics is of key importance, with subsequent decisive therapy initiated using either a conservative medical or endoscopic or surgical approach. Boerhaave's syndrome often occurs in otherwise-relatively healthy patients. This postemetic perforation of the esophagus can result in a devastating injury that usually is exacerbated by delayed diagnosis. This article will focus on its clinical presentations and review its potentially applicable therapies.

Heaton, Grant, and Matthews (1991) published procedures for adjusting raw scores on various neuropsychological tests according to the individual's age and education. Despite rather widespread use of these score conversions in both clinical work and research publications, there have been very few investigations to evaluate the accuracy or limitations of these score transformations. This study was based on 52 persons with brain damage who had a range of verified brain injuries or disease. Raw scores were transformed according to the Heaton, Grant, and Matthews (HGM) procedure and also according to Reitan and Wolfson's Neuropsychological Deficit Scale (RW NDS) score procedure. The latter method is a straightforward transformation of raw scores and does not adjust for age or education. The number of normal (vs. impaired) scores was 1.74 times greater using the Heaton, Grant, and Matthews method than when using the Reitan and Wolfson method, yielding a chi2 value of 32.66 (p < .001). These results suggest that impairment in this brain-damaged group was identified less often when using the Heaton, Grant, and Matthews procedure than when using a method that represented the raw scores directly. The clinical and forensic implications of these findings are discussed. More research on this issue is needed.

This paper presents a review and critique of the Houston Conference on Specialty Education and Training in Clinical Neuropsychology, together with an informal summary of opinions of a number of neuropsychologists. Issues regarding the role of the Clinical Neuropsychology Synarchy (CNS) and the applicability of the conference policies are offered. Several deficiencies and limitations of the policy statement are discussed. An informal survey of neuropsychologists interested in the Houston Conference indicates rather different opinions concerning the training and education of neuropsychologists. It is our contention that the results of the Houston Conference can only be considered controversial at best and that there is still much diversity of opinion in the field regarding the proper training of neuropsychologists. We hope to stimulate further discussion and greater involvement of the profession before final criteria for education and training are developed and adopted.

This study was designed to explore the possibility of using a brief neuropsychological test for broad-band initial screening of children with academic problems who might have neuropsychological deficits that should be more completely evaluated. Part B of the Trail Making Test was selected as the instrument for investigation. Three groups of children, aged 9-14 years, were composed for this study to represent (1) children with diagnosed brain damage or disease, (2) children who were medically normal but who were of serious concern to parents and teachers because of inadequate academic progress, and (3) a normal control group. The Brain-Damaged group required more than three times the number of seconds needed by the controls to complete the test, and the group with academic difficulties required more than twice the time of the controls. Using the limits set by the distributions of the Brain-Damaged and control groups, it was possible to identify a cutoff point that may be used for preliminary identification of children with academic difficulties who might benefit from further neuropsychological evaluation. The results of this study stand in need of cross-validation and, obviously, much additional outcome research is necessary to evaluate the efficacy and validity of the findings for screening purposes.

This study explores the use of the Progressive Figures Test as an instrument for broad initial screening of children in the 6- through 8-year age range with respect to the possible need for more definitive neuropsychological evaluation. Considering earlier results obtained in comparison of brain-damaged and control children [Clinical Neuropsychology: Current Applications, Hemisphere Publishing Corp., Washington, DC, 1974, p. 53; Proceedings of the Conference on Minimal Brain Dysfunction, New York Academy of Sciences, New York, 1973, p. 65], the Progressive Figures Test seemed potentially useful as a first step in determining whether a comprehensive neuropsychological evaluation is indicated. In this investigation, three groups were studied: (1) children with definitive evidence of brain damage or disease who, when compared with normal controls, help to establish the limits of neuropsychological functioning, (2) a group of children who had normal neurological examinations but also had academic problems of significant concern to both parents and teachers, and (3) a normal control group. Statistically significant differences were present in comparing each pair of groups, with the brain-damaged children performing most poorly and the controls performing best. Score distributions for the three groups make it possible to identify a score-range that represented a borderline or "gray" area and to suggest a cutting score that identified children whose academic problems might have a neurological basis and for whom additional neuropsychological evaluation appeared to be indicated.

Background: Dementia shortens life expectancy; estimates of median survival after the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people with existing dementia, however, may have underestimated the deleterious effects of dementia on survival by failing to consider persons with rapidly progressive illness who died before they could be included in a study (referred to as length bias)., Methods: We used data from the Canadian Study of Health and Aging to estimate survival from the onset of symptoms of dementia; the estimate was adjusted for length bias. A random sample of 10,263 subjects 65 years old or older from throughout Canada was screened for cognitive impairment. For those with dementia, we ascertained the date of onset and conducted follow-up for five years., Results: We analyzed data on 821 subjects, of whom 396 had probable Alzheimer's disease, 252 had possible Alzheimer's disease, and 173 had vascular dementia. For the group as a whole, the unadjusted median survival was 6.6 years (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias, the estimated median survival was 3.3 years (95 percent confidence interval, 2.7 to 4.0). The median survival was 3.1 years for subjects with probable Alzheimer's disease, 3.5 years for subjects with possible Alzheimer's disease, and 3.3 years for subjects with vascular dementia., Conclusions: Median survival after the onset of dementia is much shorter than has previously been estimated.

This article presents a critical evaluation of a Special Article, provided as an "educational service" and prepared by an Expert Panel under the direction of the Technology and Therapeutic Assessment Subcommittee of the American Academy of Neurology. The chief author of the Special Article was Jeffrey L. Cummings, M.D.

Reports in the literature have suggested that the neuropsychological effects of mild head injury are selective, represented by impairment of attention, information processing, and memory, and that evaluations with comprehensive and standard test batteries are likely to miss such deficits. The present study compared groups of individuals with mild head injuries, more severe head injuries, and non-brain-damaged controls using 19 tests from the Halstead-Reitan Battery. The results indicated that the group with mild head injuries performed significantly poorer than the controls, and that the group with more severe head injuries scored significantly more poorly than either of the other groups. Comparisons of the pattern of test scores for the two head-injured groups were remarkably similar across the 19 tests, yielding a rank difference correlation of 0.87. The findings yielded no evidence of selective or delimited impairment in the group with mild head injuries, but instead, showed them to have test results that were very similar, though showing less neuropsychological impairment, to the group of subjects with more severe head injuries. These findings suggest that a comprehensive neuropsychological test battery is necessary to detect the broad range of deficits that may result from mild head injury.

Conation, which involves the ability to apply oneself diligently and productively to the completion of a task over time, was compared in groups with and without evidence of brain damage. Both groups were administered tests that ranged from tasks that were presented by an examiner one item at a time (minimal conation), to a task that required the subject to work independently for 30 minutes, with instructions to work as quickly and as accurately as possible. In this study it was not possible to control test content perfectly, but all tasks were primarily verbal in nature. The subjects with brain damage, compared to the controls, showed progressive impairment in accordance with the degree to which the tasks were judged to require conative ability. Conation, which has been a neglected dimension of behavior in neuropsychological assessment, may be the missing link between cognitive ability and prediction of performance capabilities in everyday life. Additional research is needed to investigate further this apparently significant aspect of neuropsychological functioning.

The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.

The research literature indicates that the great majority of persons who sustain any initial neuropsychological impairment from a mild head injury recover in 1 to 3 months. Nevertheless, clinicians report that some persons with a mild head injury demonstrate signs and report symptoms suggesting that they have sustained permanent brain damage. Although this latter group contains the participants of principal clinical interest, our literature review did not identify any research that provided a comprehensive description of the neuropsychological characteristics of this important subgroup of mild head-injured persons. The present investigation compared four groups: (1) controls, (2) persons with definite traumatic brain tissue damage, (3) persons with mild head injuries routinely accessed into a research study, and (4) persons with mild head injuries who had persisting clinical signs and symptoms. The same comprehensive neuropsychological test battery was used to evaluate all four groups. All pairs of groups differed significantly in neuropsychological status, with Group 3 showing only mild impairment (approaching the level of the controls) and Group 4 showing significant impairment (approaching the level of the group with definite brain tissue damage). The results emphasize the need for a comprehensive neuropsychological examination of persons with mild head injuries who have persisting clinical problems.

In many medical experiments, data are collected across time, over a number of similar trials, or over a number of experimental units. As is the case of neuron spike train studies, these data may be in the form of counts of events per unit of time. These counts may be correlated within each trial. It is often of interest to know if the introduction of an intervention, such as the application of a stimulus, affects the distribution of the counts over the course of the experiment. In such investigations, each trial generates a sequence of data that may or may not contain a change in distribution at some point in time. Each sequence of integer counts can be viewed as arising from a Poisson process and are therefore independently distributed or as an integer-valued time series that allows for correlations between these counts. The main aim of this paper is to show how the ensemble of sample paths may be used to make inference about the distribution of the instantaneous times of change in a given population. This will be accomplished using a Bayesian hierarchical model for these change-points in time. A bonus of these models is they also allow for inference about the probability of a change in each unit and the magnitude of the effects, if any. The use of such change-point models on integer-valued time series is illustrated on neuron spike train data, although the methods can be applied to other situations where integer-valued processes arise.

The interaction and relationships between neuropsychological tests (which are principally oriented to intellectual and cognitive abilities) and tests of personality and emotional status are complex, but nevertheless important in the clinical assessment of brain-damaged persons. Are indications of emotional disturbances to be expected as a direct consequence of brain damage? If so, how can the indications of emotional disturbances be differentiated from results obtained with psychiatrically disturbed (non-brain-damaged) subjects? Some authors have presumed that emotional disturbances, such as depression, acute anxiety, etc., in their own right cause impaired performances on neuropsychological tests, whereas other authors have proposed that brain damage predisposes the individual to demonstrate evidence of emotional disturbances. If emotional disturbances cause impairment on neuropsychological tests, why is it that so many emotionally disturbed persons without brain damage tend to perform normally on neuropsychological tests? This review of relevant publications considers (1) different general approaches to these questions and their implications for neuropsychology, (2) evidence of differential sensitivity to brain damage of neuropsychological and emotional instruments, (3) the sensitivity and specificity of self-assessments and complaints of head-injured subjects, (4) MMPI findings among head-injured subjects and in interaction with neuropsychological measurements, and (5) principles and guidelines that may be of value in clinical application of findings reported in the literature.

Recent reports in the literature have explored differential relations between age and education and psychological test results in groups with brain damage and groups without brain damage. In several investigations, both adults and children have been studied, using Wechsler Adult Intelligence Scale values and subtest scores as welt as tests that are particularly sensitive to brain damage. The findings have consistently indicated that the relations between age and education and test scores are diminished or essentially absent among groups with brain damage and groups with learning disabilities, even though a strong relation (especially for education) emerged among the control groups. In this study we examined the relations between age and education and the General Neuropsychological Deficit Scale (Reitan & Wolfson, 1988) for groups with mild head injury and found that the attribute variables had minimal correlations, similar to the correlations found with participants who have sustained frank traumatic cerebral tissue damage. The results raise serious questions about the validity of adjusting neuropsychological or intellectual test scores for participants with brain damage using results for normal participants when the rational bases for making such adjustments are limited or absent.

Prior research demonstrated that the relationships between age and neuropsychological test scores are much weaker in brain-damaged adults and children than in non-brain-damaged subjects It appears that the effects of brain damage on test scores are sufficiently strong to diminish the influence of age and education Similar results have been found with learning-disabled children The present study evaluated the effect of age adjustments on WISC-R IQ values and subtest scores The results suggest that conventional scoring of the WISC-R, which requires an age adjustment to obtain the IQ, underestimates the IQs especially of older LD children, apparently reflecting the learning-disabled child's limited rate of acquisition of intellectual abilities with advancing age.

The 11 subtests of the WAIS were compared to the attribute variables of age and education in a brain-damaged group and a non-brain-damaged (control) group. Because of the validity information available for the WAIS, the subtests for the WAIS rather than the WAIS-R were studied. Data analyses compared the level of age and education (each group subdivided at the median) on WAIS subtest scores and the correlations between attribute variables and subtest scores. The results revealed a number of differences between the two groups, with age and education having a weaker and less consistent relation to WAIS subtest scores in the brain-damaged group than in the control group. The findings suggest that the relationships between attribute variables and psychological test scores are complex, and that adjusting or transforming raw scores for brain-damaged subjects according to tables based upon non-brain-damaged subjects may produce erroneous data.

Two groups of 20 head-injured subjects were studied. One group was involved in litigation related to the head injury and the other group was not involved in litigation. Every subject had been tested twice, with the intertest mean interval for the two groups ranging from 12.00 to 14.45 months, a statistically insignificant difference. Two indexes of consistency of test-retest performance, which have been reported previously (Reitan Dissimulation Index. Comparison of the distributions for the two groups on the Dissimulation Index revealed no overlap; in fact, a gap of several points separated the groups. Every litigation subject performed with less consistency than any nonlitigation subject. Using an approach based on intra-individual test comparisons shows promise of alleviating the vexing problem of invalidity of neuropsychological test results.

The consistency of responses to individual items of the Wechsler Information, Comprehension, Arithmetic, Similarities, and Vocabulary subtests on two separate testings were compared for two groups of 20 head-injured subjects. One group of subjects was involved in litigation to recover damages for deficits allegedly resulting from the head injury; the other group was not involved in any litigation. A scoring system was devised to reflect responses that were different on the second testing, and this raw score was converted to a scaled score. The Response Consistency Index represents the sum of the scaled scores for the five subtests. The Response Consistency Index scores showed that retest responses were less consistent in the litigation group than in the non-litigation group. The best cutoff point separated the groups with accuracies of 90% (litigation group) and 100% (non-litigation group). These results suggest that the approach described in this study provides an objective method that significantly differentiates between litigants and non-litigants among head-injured subjects. It would appear that litigants, either deliberately or for other reasons, fail to produce consistent responses on successive examinations.

Sherer and Adams (1993) reported "limited support" for the validity of Reitan and Wolfson's (1988) Neuropsychological Deficit Scales. The present study was designed to cross-validate one of these scales--the General Neuropsychological Deficit Scale (GNDS). The results were in relatively close agreement with the findings originally reported by Reitan and Wolfson, and indicate that the findings of Sherer and Adams also generally support the validity of the GNDS.

Asthma continues to be a leading cause for pediatric hospitalizations. A study using high-dose intravenous (i.v.) steroids early in the emergency department (ED) care of adults with acute asthma reported a 60% reduction in hospitalization rate. Limited data are available for children. We hypothesized that the addition of early administration of high-dose methylprednisolone (MP) in routine ED care of asthmatic children would reduce the need for hospitalization by 50%. Eighty-eight children with asthma, aged four to 18 years, were enrolled into a prospective, randomized, double-blind, placebo-controlled study of MP given within 45 (mean 23) minutes of arrival to the ED. After initial evaluation, children received either 2 mg/kg of MP IV or an equivalent amount of placebo (P). Patients then received the usual ED management of their acute exacerbation. Groups were similar in age, sex, and severity of illness (by asthma scoring, respiratory rate, and peak flow). ED treatment (number of aerosols and the use of theophylline) was similar for both groups. The mean time to disposition was 2.9 hours. Sixty-four percent of the children were discharged from the ED. No significant differences were found between the admission rates of the MP and P groups (41% MP vs 33% P, P = 0.44, chi 2, 95% CI for decrease in MP vs P groups -28 to +12%). The average hospital stay was shorter for those children treated with MP (79 hours vs 90 hours). We conclude that IV methylprednisolone given as an adjunct to routine ED care of children with acute asthma is unlikely to markedly reduce hospitalization rates.