Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas

BACKGROUND: Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs. METHODS: Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data. RESULTS: fL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), P_{sNfL} = 0.03; ANOVA, P_{GFAp} = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004). CONCLUSION: sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings

Integration of Data Mining Classification Techniques and Ensemble Learning for Predicting the Type of Breast Cancer Recurrence

Conservative surgery plus radiotherapy is an alternative to radical mastectomy in the early stages of breast cancer, presenting equivalent survival rates. Data mining facilitates to manage the data and provide the useful medical progression and treatment of cancerous conditions as these methods can help to reduce the number of false positive and false negative decisions. Various machine learning techniques can be used to support the doctors in effective and accurate decision making. In this paper, various classifiers have been tested for the prediction of type of breast cancer recurrence and the results show that neural networks outperform others

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved. Discussion In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Does Screening for Pain Correspond to High Quality Care for Veterans?

Routine numeric screening for pain is widely recommended, but its association with overall quality of pain care is unclear. To assess adherence to measures of pain management quality and identify associated patient and provider factors. A cross-sectional visit-based study. One hundred and forty adult VA outpatient primary care clinic patients reporting a numeric rating scale (NRS) of moderate to severe pain (four or more on a zero to ten scale). Seventy-seven providers completed a baseline survey regarding general pain management attitudes and a post-visit survey regarding management of 112 participating patients. We used chart review to determine adherence to four validated process quality indicators (QIs) including noting pain presence, pain character, and pain control, and intensifying pharmacological intervention. The average NRS was 6.7. Seventy-three percent of charts noted the presence of pain, 13.9% the character, 23.6% the degree of control, and 15.3% increased pain medication prescription. Charts were more likely to include documentation of pain presence if providers agreed that “patients want me to ask about pain” and “pain can have negative consequences on patient’s functioning”. Charts were more likely to document character of pain if providers agreed that “patients are able to rate their pain”. Patients with musculoskeletal pain were less likely to have chart documentation of character of pain. Despite routine pain screening in VA, providers seldom documented elements considered important to evaluation and treatment of pain. Improving pain care may require attention to all aspects of pain management, not just screening

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care

Development and preliminary validation of a Greek-language outpatient satisfaction questionnaire with principal components and multi-trait analyses

BACKGROUND: In the recent years there is a growing interest in Greece concerning the measurement of the satisfaction of patients who are visiting the outpatient clinics of National Health System (NHS) general acute hospitals. The aim of this study is therefore to develop a patient satisfaction questionnaire and provide its preliminary validation. METHODS: A questionnaire in Greek has been developed by literature review, researchers' on the spot observation and interviews. Pretesting has been followed by telephone surveys in two short-term general NHS hospitals in Macedonia, Greece. A proportional stratified random sample of 285 subjects and a second random sample of 100 outpatients, drawn on March 2004, have been employed for the analysis. These have resulted in scale creation via Principal Components Analysis and psychometric testing for internal consistency, test-retest and interrater reliability as well as construct validity. RESULTS: Four summated scales have emerged regarding the pure outpatient component of the patients' visits, namely medical examination, hospital environment, comfort and appointment time. Cronbach's alpha coefficients and Pearson, Spearman and intraclass correlations indicate a high degree of scale reliability and validity. Two other scales -lab appointment time and lab experience- capture the apparently distinct yet complementary visitor experience related to the radiographic and laboratory tests. Psychometric tests are equally promising, however, some discriminant validity differences lack statistical significance. CONCLUSION: The instrument appears to be reliable and valid regarding the pure outpatient experience, whereas more research employing larger samples is required in order to establish the apparent psychometric properties of the complementary radiographic and laboratory-testing process, which is only relevant to about 25% of the subjects analysed here

Has Behavioral Science Tumbled Through the Biological Looking Glass? Will Brief, Evidence-Based Training Return It From the Rabbit Hole?

Time constraints and professional demands leave practicing professionals unlikely to enroll in extended training such as a semester-long graduate course. Thus, the three-hour continuing education format has become a standard for those in practice. One may ask what sorts of training strategies optimize that format. To explore that, a three hour training program for seventy-six practicing mental health professionals, most of whom self-identified as psychologists, was devised. It made use of primarily antecedent techniques that have been shown to bring about changed perceptions on a number of topics. Content focused on two areas of importance to behavior analysts, the culture’s increasing acceptance of the biological causation model of disorders such as attentiondeficit hyperactivity disorder (ADHD), unipolar depression, anxiety disorders, and schizophrenia, and the field’s increasing reliance on medications, often to the exclusion of behavioral methods. Pre-post assessment showed that participants had changed their thinking regarding the two content areas. The authors caution that participants’ changed opinions may serve as setting events to changes in practice, but those changes are verbal. One must not assume changes in practice techniques will automatically occur

Quality Measures for the Diagnosis and Non-Operative Management of Carpal Tunnel Syndrome in Occupational Settings

Introduction: Providing higher quality medical care to workers with occupationally associated carpal tunnel syndrome (CTS) may reduce disability, facilitate return to work, and lower the associated costs. Although many workers’ compensation systems have adopted treatment guidelines to reduce the overuse of unnecessary care, limited attention has been paid to ensuring that the care workers do receive is high quality. Further, guidelines are not designed to enable objective assessments of quality of care. This study sought to develop quality measures for the diagnostic evaluation and non-operative management of CTS, including managing occupational activities and functional limitations. Methods: Using a variation of the well-established RAND/UCLA Appropriateness Method, we developed draft quality measures using guidelines and literature reviews. Next, in a two-round modified-Delphi process, a multidisciplinary panel of 11 U.S. experts in CTS rated the measures on validity and feasibility. Results: Of 40 draft measures, experts rated 31 (78%) valid and feasible. Nine measures pertained to diagnostic evaluation, such as assessing symptoms, signs, and risk factors. Eleven pertain to non-operative treatments, such as the use of splints, steroid injections, and medications. Eleven others address assessing the association between symptoms and work, managing occupational activities, and accommodating functional limitations. Conclusions: These measures will complement existing treatment guidelines by enabling providers, payers, policymakers, and researchers to assess quality of care for CTS in an objective, structured manner. Given the characteristics of previous measures developed with these methods, greater adherence to these measures will probably lead to improved patient outcomes at a population level

Coexistence of Chiari 2 malformation and moyamoya syndrome in a 17-year-old girl.

A 17-year-old female with Chiari 2 malformation developed cerebral infarction with angiographically typical bilateral moyamoya vessels manifesting as sudden onset of moderate left hemiparesis. Magnetic resonance imaging revealed multiple infarcts in the right frontal lobe, agenesis of the corpus callosum, upward herniation of the dorsal cerebellum, tectal beak of the midbrain, and downward herniation of the cerebellar vermis. Cerebral angiography demonstrated occlusion of the bilateral internal carotid arteries and basal moyamoya vessels. Single photon emission computed tomography showed significantly reduced regional cerebral blood flow in the right frontoparietal cortex. The cerebral vascular reactivity to acetazolamide was diminished in both cerebral hemispheres. She underwent superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-myo-synangiosis on the right, and on the left 6 months later. Cerebral angiography performed 4 months after the second operation showed good patency of the bypasses and substantial collateral vessels in both cerebral hemispheres. This association may have happened by chance, and a common etiology is uncertain, but a currently undetermined genomic component might have contributed to the disease progression