Factors other than the Duke criteria associated with infective endocarditis among injection drug users.

PubMed

Palepu, Anita; Cheung, Stephen S; Montessori, Valentina; Woods, Ryan; Thompson, Christopher R

2002-08-01

Modified Duke criteria were applied to consecutive injection drug users (IDUs) who were admitted to an inner-city hospital with a clinical suspicion of infective endocarditis, and the presence of any other clinical variables that were predictive of the presence of infective endocarditis was determined. Clinical data on consecutive IDUs who were hospitalized over 15 months in Vancouver were collected. Data included the admission history, and findings on physical examination and on initial laboratory investigations. Each subject's course in hospital was followed until discharge or death during the index hospitalization. Follow-up data collected included culture results, the interpretation of the echocardiogram and the discharge diagnosis. The modified Duke criteria were used for the diagnosis of infective endocarditis (definite, possible or rejected). Multiple logistic regression was used to determine what clinical variables (exclusive of the Duke criteria) available within 48 hours of presentation were independent predictors of infective endocarditis. One hundred IDUs were enrolled. Fifty-one were female, and 58 were HIV-positive. Twenty-three met the modified Duke criteria for definite infective endocarditis, and 25 had possible infective endocarditis. IDUs with definite infective endocarditis were more commonly noted to have evidence of vascular phenomena (arterial embolism, septic pulmonary infarction, mycotic aneurysm, intracranial hemorrhage or Janeway lesions) (6 [26%]) than those who had possible endocarditis (1 [4%]). Those with definite infective endocarditis more often had multiple opacities on chest radiography (56% v. < 12%), and fewer had an obvious source of infection (52% v. 72% and 81% of possible and rejected infective endocarditis, respectively). Among febrile IDUs, definite endocarditis was highly associated with having no obvious source of infection (odds ratio 3.1 [95% confidence interval 1.1-8.7]) compared with febrile IDUs with an obvious source of infection. In similarly compared groups, the presence of hematuria, proteinuria or pyuria was also predictive of definite endocarditis (odds ratio 2.9 [95% CI 1.1-8.6]). Among IDUs, the modified Duke criteria are useful for classifying cases with definite infective endocarditis and rejecting cases without infective endocarditis. The classification of possible infective endocarditis is suitable for this population.

Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.

PubMed

Filippi, Massimo; Preziosa, Paolo; Meani, Alessandro; Ciccarelli, Olga; Mesaros, Sarlota; Rovira, Alex; Frederiksen, Jette; Enzinger, Christian; Barkhof, Frederik; Gasperini, Claudio; Brownlee, Wallace; Drulovic, Jelena; Montalban, Xavier; Cramer, Stig P; Pichler, Alexander; Hagens, Marloes; Ruggieri, Serena; Martinelli, Vittorio; Miszkiel, Katherine; Tintorè, Mar; Comi, Giancarlo; Dekker, Iris; Uitdehaag, Bernard; Dujmovic-Basuroski, Irena; Rocca, Maria A

2018-02-01

In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria. Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis. Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 [0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 [0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 [0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 [0·58-0·69]). The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria. UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a case definition for clinical feline herpesvirus infection in cheetahs (Acinonyx jubatus) housed in zoos.

PubMed

Witte, Carmel L; Lamberski, Nadine; Rideout, Bruce A; Fields, Victoria; Teare, Cyd Shields; Barrie, Michael; Haefele, Holly; Junge, Randall; Murray, Suzan; Hungerford, Laura L

2013-09-01

The identification of feline herpesvirus (FHV) infected cheetahs (Acinonyx jubatus) and characterization of shedding episodes is difficult due to nonspecific clinical signs and limitations of diagnostic tests. The goals of this study were to develop a case definition for clinical FHV and describe the distribution of signs. Medical records from six different zoologic institutions were reviewed to identify cheetahs with diagnostic test results confirming FHV. Published literature, expert opinion, and results of a multiple correspondence analysis (MCA) were used to develop a clinical case definition based on 69 episodes in FHV laboratory confirmed (LC) cheetahs. Four groups of signs were identified in the MCA: general ocular signs, serious ocular lesions, respiratory disease, and cutaneous lesions. Ocular disease occurred with respiratory signs alone, with skin lesions alone, and with both respiratory signs and skin lesions. Groups that did not occur together were respiratory signs and skin lesions. The resulting case definition included 1) LC cheetahs; and 2) clinically compatible (CC) cheetahs that exhibited a minimum of 7 day's duration of the clinical sign groupings identified in the MCA or the presence of corneal ulcers or keratitis that occurred alone or in concert with other ocular signs and skin lesions. Exclusion criteria were applied. Application of the case definition to the study population identified an additional 78 clinical episodes, which represented 58 CC cheetahs. In total, 28.8% (93/322) of the population was identified as LC or CC. The distribution of identified clinical signs was similar across LC and CC cheetahs. Corneal ulcers and/or keratitis, and skin lesions were more frequently reported in severe episodes; in mild episodes, there were significantly more cheetahs with ocular-only or respiratory-only disease. Our results provide a better understanding of the clinical presentation of FHV, while presenting a standardized case definition that can both contribute to earlier diagnoses and be used for population-level studies.

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

PubMed Central

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

PubMed Central

Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Access block in NSW hospitals, 1999-2001: does the definition matter?

PubMed

Forero, Roberto; Mohsin, Mohammed; Bauman, Adrian E; Ieraci, Sue; Young, Lis; Phung, Hai N; Hillman, Kenneth M; McCarthy, Sally M; Hugelmeyer, C David

2004-01-19

To estimate the magnitude of access block and its trend over time in New South Wales hospitals, using different definitions of access block, and to explore its association with clinical and non-clinical factors. An epidemiological study using the Emergency Department Information System datasets (1 January 1999 to 31 December 2001) from a sample of 55 NSW hospitals. Prevalence of access block measured by four different definitions; strength of association between access block, type of hospital, year of presentation, mode and time of arrival, triage category (an indicator of urgency), age and sex. Rates of access block (for all four definitions) increased between 1999 and 2001 by 1%-2% per year. There were increases across all regions of NSW, but urban regions in particular. Patients presenting to Principal Referral hospitals and those who arrived at night were more likely to experience access block. After adjusting for triage category and year of presentation, the mode of arrival, time of arrival, type of hospital, age and sex were significantly associated with access block. Access block continues to increase across NSW, whatever the definition used. We recommend that hospitals in NSW and Australia move to the use of one standard definition of access block, as our study suggests there is no significant additional information emerging from the use of multiple definitions.

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

PubMed

Chapman, J; Rand, J H; Brey, R L; Levine, S R; Blatt, I; Khamashta, M A; Shoenfeld, Y

2003-01-01

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Empirical Derivation and Validation of a Clinical Case Definition for Neuropsychological Impairment in Children and Adolescents.

PubMed

Beauchamp, Miriam H; Brooks, Brian L; Barrowman, Nick; Aglipay, Mary; Keightley, Michelle; Anderson, Peter; Yeates, Keith O; Osmond, Martin H; Zemek, Roger

2015-09-01

Neuropsychological assessment aims to identify individual performance profiles in multiple domains of cognitive functioning; however, substantial variation exists in how deficits are defined and what cutoffs are used, and there is no universally accepted definition of neuropsychological impairment. The aim of this study was to derive and validate a clinical case definition rule to identify neuropsychological impairment in children and adolescents. An existing normative pediatric sample was used to calculate base rates of abnormal functioning on eight measures covering six domains of neuropsychological functioning. The dataset was analyzed by varying the range of cutoff levels [1, 1.5, and 2 standard deviations (SDs) below the mean] and number of indicators of impairment. The derived rule was evaluated by bootstrap, internal and external clinical validation (orthopedic and traumatic brain injury). Our neuropsychological impairment (NPI) rule was defined as "two or more test scores that fall 1.5 SDs below the mean." The rule identifies 5.1% of the total sample as impaired in the assessment battery and consistently targets between 3 and 7% of the population as impaired even when age, domains, and number of tests are varied. The NPI rate increases in groups known to exhibit cognitive deficits. The NPI rule provides a psychometrically derived method for interpreting performance across multiple tests and may be used in children 6-18 years. The rule may be useful to clinicians and scientists who wish to establish whether specific individuals or clinical populations present within expected norms versus impaired function across a battery of neuropsychological tests.

Public voices in pharmaceutical deliberations: negotiating "clinical benefit" in the FDA's Avastin Hearing.

PubMed

Teston, Christa B; Graham, S Scott; Baldwinson, Raquel; Li, Andria; Swift, Jessamyn

2014-06-01

This article offers a hybrid rhetorical-qualitative discourse analysis of the FDA's 2011 Avastin Hearing, which considered the revocation of the breast cancer indication for the popular cancer drug Avastin. We explore the multiplicity of stakeholders, the questions that motivated deliberations, and the kinds of evidence presented during the hearing. Pairing our findings with contemporary scholarship in rhetorical stasis theory, Mol's (2002) construct of multiple ontologies, and Callon, Lascoumes, and Barthe's (2011) "hybrid forums," we demonstrate that the FDA's deliberative procedures elides various sources of evidence and the potential multiplicity of definitions for "clinical benefit." Our findings suggest that while the FDA invited multiple stakeholders to offer testimony, there are ways that the FDA might have more meaningfully incorporated public voices in the deliberative process. We conclude with suggestions for how a true hybrid forum might be deployed.

Detection and Prevention of Learning Disorders.

ERIC Educational Resources Information Center

Yahraes, Herbert; Prestwich, Sherry

The document provides an overview of learning disabilities and described are various approaches to the detection and prevention of these handicapping conditions. Discussed in the introduction are definitions of learning disorders, the multiple nature of the handicap, and maturational lag as a cause. A section on clinical approaches covers research…

Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.

PubMed

Vergouwen, Mervyn D I; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J E; Wijdicks, Eelco F; Muizelaar, J Paul; Mendelow, A David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G; Macdonald, R Loch; Diringer, Michael N; Broderick, Joseph P; Dreier, Jens P; Roos, Yvo B W E M

2010-10-01

In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2) functional outcome. Secondary outcome measure should be clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration. Vasospasm on angiography or transcranial Doppler can also be used as an outcome measure to investigate proof of concept but should be interpreted in conjunction with DCI or functional outcome. The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.

Current Concepts in Orthopedic Management of Multiple Trauma

PubMed Central

Kucukdurmaz, Fatih; Alijanipour, Pouya

2015-01-01

Multiple trauma patients frequently present challenging clinical scenarios with musculoskeletal injuries being the most common indications for surgical procedures in these patients. Despite our substantial knowledge, a universally approved objective definition for “multiple trauma” is yet to be delineated. Several controversial aspects of economics, pathophysiology, animal models, diagnosis, management and outcome of patients with multiple trauma have recently been explored and although some progress has been made, it seems that the available evidence is still inconclusive in some occasions. This manuscript revisits several current concepts of multiple trauma that have been the focus of recent investigation. We aim to provide the reader with an updated perspective based on the most recently published literature in the field of multiple trauma. PMID:26312111

Benign multiple sclerosis: a need for a consensus.

PubMed

Glad, S B; Aarseth, J H; Nyland, H; Riise, T; Myhr, K-M

2010-01-01

To investigate the impact of different definitions on the frequency of benign multiple sclerosis (MS) in patients with a long follow-up, and to study the presence of non-motor symptoms and employment across the definitions. All patients alive (n = 188) with disease onset during 1976-1986 in Hordaland County, Norway, were clinically examined including the Expanded Disability Status Scale (EDSS) in 2003. Non-motor symptoms which included depression, cognitive impairment, fatigue and pain, and employment status were also registered. Three definitions of benign MS were used based on the following EDSS cut-off values: 2.0, 3.0 and 4.0. Two additional definitions were added using an EDSS

Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia

PubMed Central

Kim, Kyoung Min; Jang, Hak Chul; Lim, Soo

2016-01-01

Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective. PMID:27334763

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening.

PubMed

Phillips, Glenn A; Wyrwich, Kathleen W; Guo, Shien; Medori, Rossella; Altincatal, Arman; Wagner, Linda; Elkins, Jacob

2014-11-01

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective. To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing-remitting MS (RRMS) participating in a clinical trial. Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS. © The Author(s), 2014.

Rare inflammatory diseases of the white matter and mimics of multiple sclerosis and related disorders.

PubMed

Tardieu, Marc; Deiva, Kumaran

2013-12-01

The spectra of white matter neuroinflammatory diseases and pathological processes inducing inflammatory lesions in the white matter of the central nervous system are wider in children than in adults. The definitions of multiple sclerosis (MS) and of the related clinically isolated syndromes (CIS) and acute disseminated encephalomyelitis (ADEM) have been recently revised leading to a new consensus definition. However, other entities with similarities to these diseases may also develop with monophasic or relapsing white matter inflammation. These conditions include congenital immunogenetic diseases (such as hemophagocytic lymphohistiocytosis), vasculitis, and autoantibody-mediated encephalopathies (Hashimoto encephalopathy, encephalitis with anti-N-methyl-D-aspartate receptor antibodies and neuromyelitis optica). Moreover, infectious diseases, such as Lyme disease, tumors (oligodendroglioma and lymphoma), and even genetic or metabolic diseases should also be considered if the clinical course of the disease does not follow the typical pattern for ADEM or MS. This short review describes these different entities and provides information for the differential diagnosis of inflammatory diseases of the white matter. Georg Thieme Verlag KG Stuttgart · New York.

Clinical and economic burden of idiopathic pulmonary fibrosis in Quebec, Canada.

PubMed

Tarride, Jean-Eric; Hopkins, Robert B; Burke, Natasha; Guertin, Jason R; O'Reilly, Daria; Fell, Charlene D; Dion, Genevieve; Kolb, Martin

2018-01-01

Idiopathic pulmonary fibrosis (IPF), although rare, is a severe and costly disease. To estimate the clinical and economic burden of IPF over multiple years before and after diagnosis using comprehensive administrative databases for the province of Quebec, Canada. Several administrative databases from Quebec, providing information on hospital care, community care, and pharmaceuticals, were linked over a 5-year period ending March 31, 2011, which was before approval of antifibrotic drugs in Canada. Prevalent and incident IPF cases were defined using International Classification Disease-10-CA codes and International Classification Disease-9-CM codes. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases and a narrow definition that required further diagnostic testing to confirm IPF diagnosis. Incident cases had an IPF code in a particular year without any IPF code in the 2 previous years. Health care resource utilization before and after the index diagnosis date was determined and costs calculated. Costs were expressed in 2016 Canadian dollars. Over 5-years, 10,579 (mean age: 76.4; 58% male) satisfied the broad definition of IPF and 8,683 (mean age: 74.5; 57% male) satisfied the narrow definition (82% of broad). Incidences of IPF overall were 25.8 and 21.7/100,000 population for broad and narrow definitions, respectively. Three-year survival was 40% and 37% in broad and narrow cohorts, respectively. For both cohorts, health care resource utilization and costs increased several years before diagnosis ($2,721 and $7,049/patient 5 years and 2 years prior to diagnosis using a broad definition, respectively) and remained elevated for multiple years post diagnosis ($12,978 and $8,267 at 2 and 3 years postdiagnosis). Health care resource utilization and costs of IPF increase many years prior to diagnosis. Incorporating multiyear annual costs before and after diagnosis results in a higher estimate of the economic burden of IPF than previous studies using a 1-year time frame.

Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler

2011-11-15

Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001),more » salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.« less

High-risk multiple myeloma: a multifaceted entity, multiple therapeutic challenges.

PubMed

Muchtar, Eli; Magen, Hila; Gertz, Morie A

2017-06-01

The term high-risk multiple myeloma is aimed to identify a heterogeneous group of patients who are more likely to progress and die early of their disease. Therefore, recognition of these patients is crucial. With the increase in the number of treatment options, the outcome for high-risk patients has probably improved, although the true extent of this improvement remains unknown, due to both the heterogeneous components of high-risk disease and its under-representation in clinical trials. In this article, we review the definitions of high-risk disease, emphasizing the fact that no single definition can represent the entire high-risk population. In the second part, we review the treatment options available for the management of high-risk myeloma as well as our general approach for high-risk disease. In light of the poor prognosis associated with high-risk myeloma, even in the current era, new approaches for the management of this subset of patients are needed.

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

PubMed Central

Dhib-Jalbut, Suhayl; Dowling, Peter; Durelli, Luca; Ford, Corey; Giovannoni, Gavin; Halper, June; Harris, Colleen; Herbert, Joseph; Li, David; Lincoln, John A.; Lisak, Robert; Lublin, Fred D.; Lucchinetti, Claudia F.; Moore, Wayne; Naismith, Robert T.; Oehninger, Carlos; Simon, Jack; Sormani, Maria Pia

2012-01-01

It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5 to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. PMID:24453741

Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites

PubMed Central

Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Deloria Knoll, Maria; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; O’Brien, Katherine L.; Thea, Donald M.; Awori, Juliet O.; Bunthi, Charatdao; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Goswami, Doli; Hidgon, Melissa M.; Karron, Ruth A.; Kazungu, Sidi; Kourouma, Nana; Mackenzie, Grant; Moore, David P.; Mudau, Azwifari; Mwale, Magdalene; Nahar, Kamrun; Park, Daniel E.; Piralam, Barameht; Seidenberg, Phil; Sylla, Mamadou; Feikin, Daniel R.; Scott, J. Anthony G.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey

2017-01-01

Abstract Background. Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods. Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. Results. MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62–0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. Conclusions. Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection. PMID:28575355

[Chronic pancreatitis: new definition and perspectives.

PubMed

Conti Bellocchi, Maria Cristina; De Pretis, Nicolò; Amodio, Antonio; Zerbi, Alessandro; Frulloni, Luca

2018-01-01

Chronic pancreatitis has been considered over the past years as a single disease, alcohol-induced and different from acute pancreatitis, in terms of etiology and prognosis. Actually, the introduction of a new concept of chronic pancreatitis, now considered as a fibroinflammatory process caused by multiple factors (toxic-metabolic, genetic, immunologic, obstructive), allow to better understand the pathogenesis of this complex disease. Furthermore, the discover of peculiar forms of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations), different in term of clinical aspects, findings at imaging, prognosis and therapy, radically changed the concept of the disease. In this brief review, we described the impact of this new concept in the comprehension of pathogenesis, in the definition of peculiar forms of chronic pancreatitis, and in the clinical and therapeutic approach of chronic pancreatitis.

Evaluation of the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) Semantic Structure as a Terminology Model for Standardized Assessment Measures

PubMed Central

Bakken, Suzanne; Cimino, James J.; Haskell, Robert; Kukafka, Rita; Matsumoto, Cindi; Chan, Garrett K.; Huff, Stanley M.

2000-01-01

Objective: The purpose of this study was to test the adequacy of the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) semantic structure as a terminology model for standardized assessment measures. Methods: After extension of the definitions, 1,096 items from 35 standardized assessment instruments were dissected into the elements of the Clinical LOINC semantic structure. An additional coder dissected at least one randomly selected item from each instrument. When multiple scale types occurred in a single instrument, a second coder dissected one randomly selected item representative of each scale type. Results: The results support the adequacy of the Clinical LOINC semantic structure as a terminology model for standardized assessments. Using the revised definitions, the coders were able to dissect into the elements of Clinical LOINC all the standardized assessment items in the sample instruments. Percentage agreement for each element was as follows: component, 100 percent; property, 87.8 percent; timing, 82.9 percent; system/sample, 100 percent; scale, 92.6 percent; and method, 97.6 percent. Discussion: This evaluation was an initial step toward the representation of standardized assessment items in a manner that facilitates data sharing and re-use. Further clarification of the definitions, especially those related to time and property, is required to improve inter-rater reliability and to harmonize the representations with similar items already in LOINC. PMID:11062226

Clinical application of a light-pen computer system for quantitative angiography

NASA Technical Reports Server (NTRS)

Alderman, E. L.

1975-01-01

The important features in a clinical system for quantitative angiography were examined. The human interface for data input, whether an electrostatic pen, sonic pen, or light-pen must be engineered to optimize the quality of margin definition. The computer programs which the technician uses for data entry and computation of ventriculographic measurements must be convenient to use on a routine basis in a laboratory performing multiple studies per day. The method used for magnification correction must be continuously monitored.

A 26-year-old man with dyspnea and chest pain.

PubMed

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation.

A 26-year-old man with dyspnea and chest pain

PubMed Central

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation. PMID:29099006

Analysis of underlying and multiple-cause mortality data: the life table methods.

PubMed

Moussa, M A

1987-02-01

The stochastic compartment model concepts are employed to analyse and construct complete and abbreviated total mortality life tables, multiple-decrement life tables for a disease, under the underlying and pattern-of-failure definitions of mortality risk, cause-elimination life tables, cause-elimination effects on saved population through the gain in life expectancy as a consequence of eliminating the mortality risk, cause-delay life tables designed to translate the clinically observed increase in survival time as the population gain in life expectancy that would occur if a treatment protocol was made available to the general population and life tables for disease dependency in multiple-cause data.

Perspectives of rural and remote primary healthcare services on the meaning and goals of clinical governance.

PubMed

Kwedza, Ruyamuro K; Larkins, Sarah; Johnson, Julie K; Zwar, Nicholas

2017-10-01

Definitions of clinical governance are varied and there is no one agreed model. This paper explored the perspectives of rural and remote primary healthcare services, located in North Queensland, Australia, on the meaning and goals of clinical governance. The study followed an embedded multiple case study design with semi-structured interviews, document analysis and non-participant observation. Participants included clinicians, non-clinical support staff, managers and executives. Similarities and differences in the understanding of clinical governance between health centre and committee case studies were evident. Almost one-third of participants were unfamiliar with the term or were unsure of its meaning; alongside limited documentation of a definition. Although most cases linked the concept of clinical governance to key terms, many lacked a comprehensive understanding. Similarities between cases included viewing clinical governance as a management and administrative function. Differences included committee members' alignment of clinical governance with corporate governance and frontline staff associating clinical governance with staff safety. Document analysis offered further insight into these perspectives. Clinical governance is well-documented as an expected organisational requirement, including in rural and remote areas where geographic, workforce and demographic factors pose additional challenges to quality and safety. However, in reality, it is not clearly, similarly or comprehensively understood by all participants.

The increasing influence of medical image processing in clinical neuroimaging.

PubMed

Barillot, Christian

2007-01-20

This paper review the evolution of clinical neuroinformatics domain in the passed and gives an outlook how this research field will evolve in clinical neurology (e.g. Epilepsy, Multiple Sclerosis, Dementia) and neurosurgery (e.g. image guided surgery, intra-operative imaging, the definition of the Operation Room of the future). These different issues, as addressed by the VisAGeS research team, are discussed in more details and the benefits of a close collaboration between clinical scientists (radiologist, neurologist and neurosurgeon) and computer scientists are shown to give adequate answers to the series of problems which needs to be solved for a more effective use of medical images in clinical neurosciences.

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening

PubMed Central

Wyrwich, Kathleen W; Guo, Shien; Medori, Rossella; Altincatal, Arman; Wagner, Linda; Elkins, Jacob

2014-01-01

Background: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient’s perspective. Objective: To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing–remitting MS (RRMS) participating in a clinical trial. Methods: Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results: Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). Conclusion: These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS. PMID:24740371

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

PubMed Central

Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

2016-01-01

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID:26903338

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

2016-02-23

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Putting the puzzle together: the role of 'problem definition' in complex clinical judgement.

PubMed

Cristancho, Sayra; Lingard, Lorelei; Forbes, Thomas; Ott, Michael; Novick, Richard

2017-02-01

We teach judgement in pieces; that is, we talk about each aspect separately (patient, plan, resources, technique, etc.). We also let trainees figure out how to put the pieces together. In complex situations, this might be problematic. Using data from a drawing-based study on surgeons' experiences with complex situations, we explore the notion of 'problem definition' in real-world clinical judgement using the theoretical lens of systems engineering. 'Emergence', the sensitising concept for analysis, is rooted in two key systems premises: that person and context are inseparable and that what emerges is an act of choice. Via a 'gallery walk' we used these premises to perform analysis on individual drawings as well as cross-comparisons of multiple drawings. Our focus was to understand similarities and differences among the vantage points used by multiple surgeons. In this paper we challenge two assumptions from current models of clinical judgement: that experts hold a fixed and static definition of the problem and that consequently the focus of the expert's work is on solving the problem. Each situation described by our participants revealed different but complementary perspectives of what a surgical problem might come to be: from concerns about ensuring standard of care, to balancing personal emotions versus care choices, to coordinating resources, and to maintaining control while in the midst of personality clashes. We suggest that it is only at the situation and system level, not at the individual level, that we are able to appreciate the nuances of defining the problem when experts make judgements during real-world complex situations. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis.

PubMed

Wattjes, Mike P; Harzheim, Michael; Lutterbey, Götz G; Bogdanow, Manuela; Schmidt, Stephan; Schild, Hans H; Träber, Frank

2008-02-01

The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS.

How Important are the Laws of Definite and Multiple Proportions in Chemistry and Teaching Chemistry? A History and Philosophy of Science Perspective

NASA Astrophysics Data System (ADS)

Niaz, Mansoor

The main objectives of this study are:(1) to elaborate a framework based on a rational reconstruction of developments that led to the formulation of the laws of definite and multiple proportions; (2) to ascertain students' views of the two laws; (3) to formulate criteria based on the framework for evaluating chemistry textbooks' treatment of the two laws; and (4) to provide a rationale for chemistry teachers to respond to the question: Can we teach chemistry without the laws of definite and multiple proportions? Results obtained show that most of the textbooks present the laws of definite and multiple proportions within an inductivist perspective, characterized by the following sequence: experimental findings showed that chemical elements combined in fixed/multiple proportions, followed by the formulation of the laws of definite and multiple proportions, and finally Dalton's atomic theory was postulated to explain the laws. Students were found to be reluctant to question the laws that they learnt as the building blocks of chemistry. It is concluded that by emphasizing the laws of definite and multiple proportions, textbooks inevitably endorse the dichotomy between theories and laws, which is questioned by philosophers of science (Lakatos 1970; Giere 1995a, b). An alternative approach is presented which shows that we can teach chemistry without the laws of definite and multiple proportions.

The Impact of Family Violence on Children and Adolescents. Developmental Clinical Psychology and Psychiatry, Volume 37.

ERIC Educational Resources Information Center

Kashani, Javad H.; Allan, Wesley D.

Violence in the family is being increasingly identified as a societal problem that has multiple short- and long-term effects on children. This book focuses on the relationship between different types of family violence and the resulting impact of violence on the child. Chapter One discusses the definition, history, and societal costs of family…

Subclinical visual involvement in multiple sclerosis: a study by MRI, VEPs, frequency-doubling perimetry, standard perimetry, and contrast sensitivity.

PubMed

Sisto, Dario; Trojano, Maria; Vetrugno, Michele; Trabucco, Tiziana; Iliceto, Giovanni; Sborgia, Carlo

2005-04-01

To evaluate the effectiveness of visual evoked potentials (VEPs), frequency-doubling perimetry (FDP), standard achromatic perimetry (SAP), contrast sensitivity (CS) test, and magnetic resonance imaging (MRI), isolated or in combination, in detecting subclinical impairment of visual function in multiple sclerosis (MS). Twenty-two eyes of 11 patients affected by clinically definite MS, without a history of optic neuritis and asymptomatic for visual disturbances, underwent full ophthalmic examination and, in addition, VEPs, FDP, SAP, CS, and MRI. Abnormal results were taken to be as follows: for VEPs, a P100 latency >115 ms; for FDP, abnormal mean deviation (MD) or pattern SD (PSD); for SAP, abnormal MD or PSD; for CS, abnormal CS at one spatial frequency, at least; and for MRI, evidence of at least one demyelinating plaque along the visual pathway. VEPs showed abnormal results in 12 eyes (54.4%), FDP in 11 (50%), SAP in 14 (63.6%), CS in 17 (77.1%), and MRI in 16 (72.7%). In only two (9.1%) eyes of the same patient was no abnormality found. No single test detected all the abnormal eyes. Four (18.2%) eyes had pure optic nerve involvement and the remaining 16 (72.7%) had both pre- and postchiasmal involvement. In patients affected by clinically definite MS without history of optic neuritis and no visual symptoms, there is a large prevalence of visual pathway involvement that can be diagnosed only by performing multiple tests. The comparison of the tests is also useful to detect the presence of multiple lesions in the same patient.

Multimodality Tumor Delineation and Predictive Modelling via Fuzzy-Fusion Deformable Models and Biological Potential Functions

NASA Astrophysics Data System (ADS)

Wasserman, Richard Marc

The radiation therapy treatment planning (RTTP) process may be subdivided into three planning stages: gross tumor delineation, clinical target delineation, and modality dependent target definition. The research presented will focus on the first two planning tasks. A gross tumor target delineation methodology is proposed which focuses on the integration of MRI, CT, and PET imaging data towards the generation of a mathematically optimal tumor boundary. The solution to this problem is formulated within a framework integrating concepts from the fields of deformable modelling, region growing, fuzzy logic, and data fusion. The resulting fuzzy fusion algorithm can integrate both edge and region information from multiple medical modalities to delineate optimal regions of pathological tissue content. The subclinical boundaries of an infiltrating neoplasm cannot be determined explicitly via traditional imaging methods and are often defined to extend a fixed distance from the gross tumor boundary. In order to improve the clinical target definition process an estimation technique is proposed via which tumor growth may be modelled and subclinical growth predicted. An in vivo, macroscopic primary brain tumor growth model is presented, which may be fit to each patient undergoing treatment, allowing for the prediction of future growth and consequently the ability to estimate subclinical local invasion. Additionally, the patient specific in vivo tumor model will be of significant utility in multiple diagnostic clinical applications.

Temporomandibular joint disorder in a patient with multiple sclerosis--review of literature with a clinical report.

PubMed

Badel, Tomislav; Carek, Andreja; Podoreski, Dijana; Pavicin, Ivana Savić; Lovko, Sandra Kocijan

2010-09-01

Temporomandibular disorders are a form of musculoskeletal disorders, which reduce the function of stomatognathic system and they are related to some other diseases causing painful conditions and disorders of oral function. The aim of this paper is to describe a one year follow up clinical case of a female patient with comorbid multiple sclerosis and a relatively rare form of articular disc disorder. Primary clinical diagnostics encompassed manual methods of TMJ examination. Definite diagnosis included radiologic examination. Clinical hyperextensive condyle position was palpated bilaterally and subsequently confirmed by a functional panoramic radiograph of TMJ. The anterior displacement of disc with reduction was diagnosed by magnetic resonance and in the right joint there was a disc displacement upon excursive movement. From relevant literature, the relationship of a number of diseases that can be related to functional disorder of the orofacial system, such as multiple sclerosis, has been described from many aspects. Also, apart from the standard classification of one form of anterior displacement of the disc, made primarily by magnetic resonance, cases of disc displacement upon excursive mandibular movement can rarely be found in literature.

[Nosology and etiologies of acute longitudinally extensive transverse myelitis].

PubMed

Collongues, N; Papeix, C; Zéphir, H; Audoin, B; Cotton, F; Durand-Dubief, F; Vukusic, S; Brassat, D; Laplaud, D; Marignier, R

2014-01-01

Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Searching for a relevant definition of sarcopenia: results from the cross-sectional EPIDOS study

PubMed Central

Dupuy, Charlotte; Lauwers-Cances, Valérie; Guyonnet, Sophie; Gentil, Catherine; Abellan Van Kan, Gabor; Beauchet, Olivier; Schott, Anne-Marie; Vellas, Bruno; Rolland, Yves

2015-01-01

Background The diversity of definitions proposed for sarcopenia has been rarely tested in the same population, and so far, their clinical utilities for predicting physical difficulties could not be clearly understood. Our objective is to report the prevalence of sarcopenia and the characteristics of sarcopenic community-dwelling older women according to the different definitions of sarcopenia currently proposed. We also assessed these definitions for their incremental predictive value over currently standard predictors for some self-reported difficulties in physical function and knee extension strength. Methods Cross-sectional analysis included data from 3025 non-disabled women aged 75 years or older without previous history of hip fracture from the inclusion visit of the EPIDémiologie de l'OStéoporose study. A total body composition evaluation was available for 2725 women. Sarcopenia was defined using six different definitions of sarcopenia based on different muscle mass, gait speed, and grip strength cut-offs. Self-reported difficulties in physical function and knee extension strength were collected. Logistic regression and multiple linear regression models were built for each physical dysfunction, and the predictive capacity of sarcopenia (one model for each definition) was studied using the C-statistic, the net reclassification index, or adjusted R2. Results The estimated prevalence of sarcopenia ranged from 3.3–20.0%. Only 85 participants (3.1%) were identified having sarcopenia according to all definitions. All definitions were, to some degree, associated with self-reported difficulties in physical function and knee extension strength, but none improved the predictive ability of the self-reported difficulties in physical function. Conversely, all definitions accounted for a small but significant amount of explained variation for predicting knee extension strength. Conclusions Prevalence of sarcopenia varies widely depending on the definition adopted. Based on this research, the current definitions for sarcopenia does not substantially increment the predictive value of clinical characteristics of patients to predict self-reported physical difficulties and knee extension strength. PMID:26136190

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Transformation of Follicular Lymphoma

PubMed Central

Lossos, Izidore S.; Gascoyne, Randy D.

2011-01-01

Histological transformation of follicular lymphoma (FL) to a more aggressive non-Hodgkin's lymphomas is a pivotal event in the natural history of FL and is associated with poor outcome. While commonly observed in clinical practice and despite multiple studies designed to address its pathogenesis, the biology of this process represents an enigma. In this chapter we present a state of the art review summarizing the definition of histologic transformation, its incidence, pathogenesis, clinical manifestations, treatment and outcome. Furthermore, we specifically emphasize gaps in our knowledge that should be addressed in future studies. PMID:21658615

Identification of appropriate patients for cardiometabolic risk management.

PubMed

Peters, Anne L

2007-01-01

Patients at increased risk for cardiovascular disease have a wide array of clinical features that should alert practitioners to the need for risk reduction. Some, but not all, of these features relate to insulin resistance. Multiple approaches exist for diagnosing and defining this risk, including the traditional Framingham risk assessment, various definitions of the metabolic syndrome, and assessment of risk factors not commonly included in the standard criteria. This article reviews the many clinical findings that should alert healthcare providers to the need for aggressive cardiovascular risk reduction.

Multifocal Neuropathy: Expanding the Scope of Double Crush Syndrome.

PubMed

Cohen, Brian H; Gaspar, Michael P; Daniels, Alan H; Akelman, Edward; Kane, Patrick M

2016-12-01

Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms. This paper examines the history of DCS and multifocal neuropathy, including the epidemiology and pathophysiology in addition to principles of evaluation and management. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial.

PubMed

Leist, Thomas P; Comi, Giancarlo; Cree, Bruce A C; Coyle, Patricia K; Freedman, Mark S; Hartung, Hans-Peter; Vermersch, Patrick; Casset-Semanaz, Florence; Scaramozza, Matthew

2014-03-01

Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5.0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Of 903 participants assessed for eligibility, 616 patients received cladribine 5.25 mg/kg (n=204), cladribine 3.5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5.25 mg/kg=0.38, 95% CI 0.25-0.58, p<0.0001; HR for 3.5 mg/kg=0.33, 0.21-0.51, p<0.0001). Adverse events were reported in 165 (81%) patients in the cladribine 5.25 mg/kg group, 168 (82%) patients in the cladribine 3.5 mg/kg group, and 162 (79%) patients in the placebo group. We noted no increase in risk of adverse events with active treatment versus placebo apart from lymphopenia, which was a severe event in 10 (5%) patients in the 5.25 mg/kg group and four (2%) patients in the 3.5 mg/kg group. Both doses of cladribine significantly delayed MS diagnosis compared with placebo. The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS. Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS. Merck Serono SA Geneva, a subsidiary of Merck KGaA, Darmstadt, Germany. Copyright © 2014 Elsevier Ltd. All rights reserved.

Periodontal disease and oral health-related behavior as factors associated with preterm birth: a case-control study in south-eastern Brazil.

PubMed

Macedo, J F; Ribeiro, R A; Machado, F C; Assis, N M S P; Alves, R T; Oliveira, A S; Ribeiro, L C

2014-08-01

Several studies have suggested a link between periodontal disease and preterm birth, but the mechanism of how this occurs remains controversial. Therefore, this study aimed to investigate whether periodontal disease, defined according to two commonly used clinical definitions, is associated with preterm birth and to examine the association regarding oral health-related behaviors during pregnancy. This case-control study included women 18-40 years of age. Demographic and socio-economic data, information on current and previous pregnancies, and data on dental health-related behaviors and periodontal clinical parameters were collected within 48 h postpartum. Periodontal disease was assessed according to two definitions: four or more teeth with at least one site showing a probing depth of ≥ 4 mm and clinical attachment level of ≥ 3 mm (Definition 1); or at least one site with probing depth and clinical attachment level of ≥ 4 mm (Definition 2). The chi-square test was used to examine differences in the proportion of categorical variables. Bivariate analysis was performed to analyze the proportion of preterm births with respect to independent variables. Multiple logistic regression analyses were used to assess the association between periodontal disease and preterm birth. Odds ratios (ORs) were calculated with a 95% confidence interval (95% CI). A total of 296 postpartum women met the inclusion criteria. The case group included 74 women who delivered a preterm neonate (< 37 wk of gestation) and the control group included 222 women with deliveries at term (≥ 37 wk). Periodontal disease according to Definition 1 was not associated with fewer weeks of gestation (adjusted OR (OR adjusted ) = 1.62; 95% CI = 0.80-3.29; p = 0.178). However, a significant association was found between periodontal disease, according to Definition 2, and preterm birth (OR adjusted = 1.98; 95% CI = 1.14-3.43; p = 0.015). Increased appetite and a low number of daily toothbrushings were associated with preterm birth, regardless of the definition of periodontal disease used. Periodontal disease defined according to Definition 2 and unfavorable oral health-related behavior were factors associated with preterm birth. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Accuracy of Digital vs Conventional Implant Impression Approach: A Three-Dimensional Comparative In Vitro Analysis.

PubMed

Basaki, Kinga; Alkumru, Hasan; De Souza, Grace; Finer, Yoav

To assess the three-dimensional (3D) accuracy and clinical acceptability of implant definitive casts fabricated using a digital impression approach and to compare the results with those of a conventional impression method in a partially edentulous condition. A mandibular reference model was fabricated with implants in the first premolar and molar positions to simulate a patient with bilateral posterior edentulism. Ten implant-level impressions per method were made using either an intraoral scanner with scanning abutments for the digital approach or an open-tray technique and polyvinylsiloxane material for the conventional approach. 3D analysis and comparison of implant location on resultant definitive casts were performed using laser scanner and quality control software. The inter-implant distances and interimplant angulations for each implant pair were measured for the reference model and for each definitive cast (n = 20 per group); these measurements were compared to calculate the magnitude of error in 3D for each definitive cast. The influence of implant angulation on definitive cast accuracy was evaluated for both digital and conventional approaches. Statistical analysis was performed using t test (α = .05) for implant position and angulation. Clinical qualitative assessment of accuracy was done via the assessment of the passivity of a master verification stent for each implant pair, and significance was analyzed using chi-square test (α = .05). A 3D error of implant positioning was observed for the two impression techniques vs the reference model, with mean ± standard deviation (SD) error of 116 ± 94 μm and 56 ± 29 μm for the digital and conventional approaches, respectively (P = .01). In contrast, the inter-implant angulation errors were not significantly different between the two techniques (P = .83). Implant angulation did not have a significant influence on definitive cast accuracy within either technique (P = .64). The verification stent demonstrated acceptable passive fit for 11 out of 20 casts and 18 out of 20 casts for the digital and conventional methods, respectively (P = .01). Definitive casts fabricated using the digital impression approach were less accurate than those fabricated from the conventional impression approach for this simulated clinical scenario. A significant number of definitive casts generated by the digital technique did not meet clinically acceptable accuracy for the fabrication of a multiple implant-supported restoration.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

PubMed

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-09-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). © 2015 British Society for Immunology.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

PubMed Central

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-01-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; http://www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; http://www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). PMID:25959571

From problem solving to problem definition: scrutinizing the complex nature of clinical practice.

PubMed

Cristancho, Sayra; Lingard, Lorelei; Regehr, Glenn

2017-02-01

In medical education, we have tended to present problems as being singular, stable, and solvable. Problem solving has, therefore, drawn much of medical education researchers' attention. This focus has been important but it is limited in terms of preparing clinicians to deal with the complexity of the 21st century healthcare system in which they will provide team-based care for patients with complex medical illness. In this paper, we use the Soft Systems Engineering principles to introduce the idea that in complex, team-based situations, problems usually involve divergent views and evolve with multiple solution iterations. As such we need to shift the conversation from (1) problem solving to problem definition, and (2) from a problem definition derived exclusively at the level of the individual to a definition derived at the level of the situation in which the problem is manifested. Embracing such a focus on problem definition will enable us to advocate for novel educational practices that will equip trainees to effectively manage the problems they will encounter in complex, team-based healthcare.

A comparison of multiple imputation methods for incomplete longitudinal binary data.

PubMed

Yamaguchi, Yusuke; Misumi, Toshihiro; Maruo, Kazushi

2018-01-01

Longitudinal binary data are commonly encountered in clinical trials. Multiple imputation is an approach for getting a valid estimation of treatment effects under an assumption of missing at random mechanism. Although there are a variety of multiple imputation methods for the longitudinal binary data, a limited number of researches have reported on relative performances of the methods. Moreover, when focusing on the treatment effect throughout a period that has often been used in clinical evaluations of specific disease areas, no definite investigations comparing the methods have been available. We conducted an extensive simulation study to examine comparative performances of six multiple imputation methods available in the SAS MI procedure for longitudinal binary data, where two endpoints of responder rates at a specified time point and throughout a period were assessed. The simulation study suggested that results from naive approaches of a single imputation with non-responders and a complete case analysis could be very sensitive against missing data. The multiple imputation methods using a monotone method and a full conditional specification with a logistic regression imputation model were recommended for obtaining unbiased and robust estimations of the treatment effect. The methods were illustrated with data from a mental health research.

Accuracy of Zika virus disease case definition during simultaneous Dengue and Chikungunya epidemics.

PubMed

Braga, José Ueleres; Bressan, Clarisse; Dalvi, Ana Paula Razal; Calvet, Guilherme Amaral; Daumas, Regina Paiva; Rodrigues, Nadia; Wakimoto, Mayumi; Nogueira, Rita Maria Ribeiro; Nielsen-Saines, Karin; Brito, Carlos; Bispo de Filippis, Ana Maria; Brasil, Patrícia

2017-01-01

Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barré syndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic. We evaluated the accuracy of various Zika case definitions in a scenario where Dengue and Chikungunya viruses co-circulate. Signs and symptoms that best discriminated PCR confirmed Zika from other laboratory confirmed febrile or exanthematic diseases were identified to propose and test predictive models for Zika infection based on these clinical features. Our derived score prediction model had the best performance because it demonstrated the highest sensitivity and specificity, 86·6% and 78·3%, respectively. This Zika case definition also had the highest values for auROC (0·903) and R2 (0·417), and the lowest Brier score 0·096. In areas where multiple arboviruses circulate, the presence of rash with pruritus or conjunctival hyperemia, without any other general clinical manifestations such as fever, petechia or anorexia is the best Zika case definition.

Revised surveillance case definition for HIV infection--United States, 2014.

PubMed

2014-04-11

Following extensive consultation and peer review, CDC and the Council of State and Territorial Epidemiologists have revised and combined the surveillance case definitions for human immunodeficiency virus (HIV) infection into a single case definition for persons of all ages (i.e., adults and adolescents aged ≥13 years and children aged <13 years). The revisions were made to address multiple issues, the most important of which was the need to adapt to recent changes in diagnostic criteria. Laboratory criteria for defining a confirmed case now accommodate new multitest algorithms, including criteria for differentiating between HIV-1 and HIV-2 infection and for recognizing early HIV infection. A confirmed case can be classified in one of five HIV infection stages (0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV test within 6 months of HIV diagnosis, is classified as stage 0, and acquired immunodeficiency syndrome (AIDS) is classified as stage 3. Criteria for stage 3 have been simplified by eliminating the need to differentiate between definitive and presumptive diagnoses of opportunistic illnesses. Clinical (nonlaboratory) criteria for defining a case for surveillance purposes have been made more practical by eliminating the requirement for information about laboratory tests. The surveillance case definition is intended primarily for monitoring the HIV infection burden and planning for prevention and care on a population level, not as a basis for clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection using this revised surveillance case definition.

Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study.

PubMed

Wyller, Vegard B; Helland, Ingrid B

2013-02-07

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.

The ISMAAR proposal on terminology for ovarian stimulation for IVF.

PubMed

Nargund, G; Fauser, B C J M; Macklon, N S; Ombelet, W; Nygren, K; Frydman, R

2007-11-01

IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient-centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients.

Validating archetypes for the Multiple Sclerosis Functional Composite.

PubMed

Braun, Michael; Brandt, Alexander Ulrich; Schulz, Stefan; Boeker, Martin

2014-08-03

Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions.This case study provides evidence that both community- and tool-enabled review processes, structured in the Clinical Knowledge Manager, ensure archetype quality. It offers a pragmatic but feasible way to reduce variation in the representation of clinical information models towards a more unified and interoperable model.

Validating archetypes for the Multiple Sclerosis Functional Composite

PubMed Central

2014-01-01

Background Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. Methods A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Results Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. Conclusions The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions. This case study provides evidence that both community- and tool-enabled review processes, structured in the Clinical Knowledge Manager, ensure archetype quality. It offers a pragmatic but feasible way to reduce variation in the representation of clinical information models towards a more unified and interoperable model. PMID:25087081

Fusion Simulation Program Definition. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cary, John R.

2012-09-05

We have completed our contributions to the Fusion Simulation Program Definition Project. Our contributions were in the overall planning with concentration in the definition of the area of Software Integration and Support. We contributed to the planning of multiple meetings, and we contributed to multiple planning documents.

Pain clinic definitions in the medical literature and U.S. state laws: an integrative systematic review and comparison.

PubMed

Andraka-Christou, Barbara; Rager, Joshua B; Brown-Podgorski, Brittany; Silverman, Ross D; Watson, Dennis P

2018-05-22

In response to widespread opioid misuse, ten U.S. states have implemented regulations for facilities that primarily manage and treat chronic pain, called "pain clinics." Whether a clinic falls into a state's pain clinic definition determines the extent to which it is subject to oversight. It is unclear whether state pain clinic definitions model those found in the medical literature, and potential differences lead to discrepancies between scientific and professionally guided advice found in the medical literature and actual pain clinic practice. Identifying discrepancies could assist states to design laws that are more compatible with best practices suggested in the medical literature. We conducted an integrative systematic review to create a taxonomy of pain clinic definitions using academic medical literature. We then identified existing U.S. state pain clinic statutes and regulations and compared the developed taxonomy using a content analysis approach to understand the extent to which medical literature definitions are reflected in state policy. In the medical literature, we identified eight categories of pain clinic definitions: 1) patient case mix; 2) single-modality treatment; 3) multidisciplinary treatment; 4) interdisciplinary treatment; 5) provider supervision; 6) provider composition; 7) marketing; and 8) outcome. We identified ten states with pain clinic laws. State laws primarily include the following definitional categories: patient case mix; single-modality treatment, and marketing. Some definitional categories commonly found in the medical literature, such as multidisciplinary treatment and interdisciplinary treatment, rarely appear in state law definitions. This is the first study to our knowledge to develop a taxonomy of pain clinic definitions and to identify differences between pain clinic definitions in U.S. state law and medical literature. Future work should explore the impact of different legal pain clinic definitions on provider decision-making and state-level health outcomes.

Management of status epilepticus.

PubMed

Pichler, M; Hocker, S

2017-01-01

Status epilepticus is a neurologic and medical emergency manifested by prolonged seizure activity or multiple seizures without return to baseline. It is associated with substantial medical cost, morbidity, and mortality. There is a spectrum of severity dependent on the type of seizure, underlying pathology, comorbidities, and appropriate and timely medical management. This chapter discusses the evolving definitions of status epilepticus and multiple patient and clinical factors which influence outcome. The pathophysiology of status epilepticus is reviewed to provide a better understanding of the mechanisms which contribute to status epilepticus, as well as the potential long-term effects. The clinical presentations of different types of status epilepticus in adults are discussed, with emphasis on the hospital course and management of the most dangerous type, generalized convulsive status epilepticus. Strategies for the evaluation and management of status epilepticus are provided based on available evidence from clinical trials and recommendations from the Neurocritical Care Society and the European Federation of Neurological Societies. © 2017 Elsevier B.V. All rights reserved.

Halitosis: a new definition and classification.

PubMed

Aydin, M; Harvey-Woodworth, C N

2014-07-11

There is no universally accepted, precise definition, nor standardisation in terminology and classification of halitosis. To propose a new definition, free from subjective descriptions (faecal, fish odour, etc), one-time sulphide detector readings and organoleptic estimation of odour levels, and excludes temporary exogenous odours (for example, from dietary sources). Some terms previously used in the literature are revised. A new aetiologic classification is proposed, dividing pathologic halitosis into Type 1 (oral), Type 2 (airway), Type 3 (gastroesophageal), Type 4 (blood-borne) and Type 5 (subjective). In reality, any halitosis complaint is potentially the sum of these types in any combination, superimposed on the Type 0 (physiologic odour) present in health. This system allows for multiple diagnoses in the same patient, reflecting the multifactorial nature of the complaint. It represents the most accurate model to understand halitosis and forms an efficient and logical basis for clinical management of the complaint.

The development of platinum compounds and their possible combination.

PubMed

Pasetto, Lara Maria; D'Andrea, Mario Rosario; Brandes, Alba Ariela; Rossi, Elena; Monfardini, Silvio

2006-10-01

Cisplatin plays a central role in cancer chemotherapy in spite of its toxicity. To circumvent this toxicity and to enhance its therapeutic index a lot of preclinical and clinical studies have been conducted and several thousand analogues have been synthesized. Much more analysis remains to be done, but nowadays, the absence of any definitive, biologically interpretable molecular predictor of activity is consistent with the idea that platinum compounds have multiple intracellular targets and that cells can have multiple mechanisms of resistance. This review analyses a part of these platinum compounds analyzed to date, their mechanism of action, resistance and the future trends in this sector.

The Importance of Clinical Phenotype in Understanding and Preventing Spontaneous Preterm Birth.

PubMed

Esplin, M Sean

2016-02-01

Spontaneous preterm birth (SPTB) is a well-known cause of maternal and neonatal morbidity. The search for the underlying pathways, documentation of the genetic causes, and identification of markers of spontaneous PTB have been marginally successful due to the fact that it is highly complex, with numerous processes that lead to a final common pathway. There is a great need for a comprehensive, consistent, and uniform classification system, which will be useful in identifying mechanisms, assigning prognosis, aiding in clinical management, and can identify areas of interest for intervention and future study. Effective classification systems must overcome obstacles including the lack of widely accepted definitions and uncertainty about inclusion of classifying features (e.g., presentation at delivery and multiple gestations) and levels of detail of these features. The optimal classification system should be based on the clinical phenotype, including characteristics of the mother, fetus, placenta, and the presentation for delivery. We present a proposed phenotyping system for spontaneous PTB. Future classification systems must establish a universally accepted set of definitions and a standardized clinical workup for all PTBs including the minimum clinical data to be collected and the laboratory and pathologic evaluation that should be completed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Interpretation on Chinese surgeons' consensus opinion for the definition of gastric stump cancer (version 2018)].

PubMed

Gao, Zhidong; Jiang, Kewei; Ye, Yingjiang; Wang, Shan

2018-05-25

Gastric stump cancer(GSC) is defined as newly developed remnant stomach cancer following gastrectomy. This definition initially referred to carcinoma detected in the remnant stomach more than 5 years after the primary surgery for a benign disease. Subsequently, this timeframe was extended to 10 years after the primary surgery for a malignant disease. Recently, the concept of "carcinoma in the remnant stomach(CRS)" proposed by the Japanese Gastric Cancer Association was introduced in China. The new definition encompasses all carcinomas arising in the remnant stomach following gastrectomy, irrespective of the histology of the primary lesion, extent of resection, or reconstruction method. It includes all carcinoma types that have developed in the remnant stomach, such as newly developed cancer, recurrent cancer, remaining cancer, and multiple cancers. Considering the current diagnosis and treatment status of gastric cancer in China, if CRS is to be used as a direct equivalent to GSC in clinical practice, confusion may arise concerning disease identification and diagnosis. Following several discussion rounds, a meta-analysis of the literatures at home and abroad, and a multicenter national retrospective study with a large sample population, the "Chinese surgeons' consensus opinion for the definition of gastric stump cancer (version 2018)" was completed. By reviewing the detailed evidence-based medicine supporting the consensus document, this paper aims to assist clinical diagnosis and enhance future academic exchange.

The interpretation of physical activity, exercise, and sedentary behaviours by persons with multiple sclerosis.

PubMed

Kinnett-Hopkins, Dominique; Learmonth, Yvonne; Hubbard, Elizabeth; Pilutti, Lara; Roberts, Sarah; Fanning, Jason; Wójcicki, Thomas; McAuley, Edward; Motl, Robert

2017-11-07

This study adopted a qualitative research design with directed content analysis and examined the interpretations of physical activity, exercise, and sedentary behaviour by persons with multiple sclerosis. Fifty three persons with multiple sclerosis who were enrolled in an exercise trial took part in semi-structured interviews regarding personal interpretations of physical activity, exercise, and sedentary behaviours. Forty three percent of participants indicated a consistent understanding of physical activity, 42% of participants indicated a consistent understanding of exercise, and 83% of participants indicated a consistent understanding of sedentary behaviour with the standard definitions. There was evidence of definitional ambiguity (i.e., 57, 58, and 11% of the sample for physical activity, exercise, and sedentary behaviour, respectively); 6% of the sample inconsistently defined sedentary behaviour with standard definitions. Some participants described physical activity in a manner that more closely aligned with exercise and confused sedentary behaviour with exercise or sleeping/napping. Results highlight the need to provide and utilise consistent definitions for accurate understanding, proper evaluation and communication of physical activity, exercise, and sedentary behaviours among persons with multiple sclerosis. The application of consistent definitions may minimise ambiguity, alleviate the equivocality of findings in the literature, and translate into improved communication about these behaviours in multiple sclerosis. Implications for Rehabilitation The symptoms of multiple sclerosis can be managed through participation in physical activity and exercise. Persons with multiple sclerosis are not engaging in sufficient levels of physical activity and exercise for health benefits. Rehabilitation professionals should use established definitions of physical activity, exercise, and sedentary behaviours when communicating about these behaviours among persons with multiple sclerosis.

Congenital malformations of the skull and meninges.

PubMed

Kanev, Paul M

2007-02-01

The surgery and management of children who have congenital malformations of the skull and meninges require multidisciplinary care and long-term follow-up by multiple specialists in birth defects. The high definition of three-dimensional CT and MRI allows precise surgery planning of reconstruction and management of associated malformations. The reconstruction of meningoencephaloceles and craniosynostosis are challenging procedures that transform the child's appearance. The embryology, clinical presentation, and surgical management of these malformations are reviewed.

Effects of Test Expectation on Multiple-Choice Performance and Subjective Ratings

ERIC Educational Resources Information Center

Balch, William R.

2007-01-01

Undergraduates studied the definitions of 16 psychology terms, expecting either a multiple-choice (n = 132) or short-answer (n = 122) test. All students then received the same multiple-choice test, requiring them to recognize the definitions as well as novel examples of the terms. Compared to students expecting a multiple-choice test, those…

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

PubMed

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-08

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation

PubMed Central

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-01

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a ‘false-negative’ result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death. PMID:23302550

A squamous cell lung carcinoma with abscess-like distant metastasis.

PubMed

Dursunoğlu, Neşe; Başer, Sevin; Evyapan, Fatma; Kiter, Göksel; Ozkurt, Sibel; Polat, Bahattin; Karabulut, Nevzat

2007-01-01

This is a metastatic spread of squamous cell lung carcinoma to lungs, liver, lymph node, bone and subcutanous region as multiple abscess-like lesions. A fifty-five years old man admitted to the out-patient clinic with fever, cough, hemopthysis, night sweats, chest pain, abdominal pain and weight loss. In a short period of time abcess like lesions developed in his lungs, liver, lymph node, bone and subcutanous region. Though the clinical presentation is suggestive for an infectious condition, no success to antimicrobial treatment and negative results of microbiological studies have arised a need to further investigations. Histopathological studies of the abscess wall ultimately gave the definitive diagnosis as metastatic squamous cell carcinoma. We believe that case report is interesting because of the uncommon metastatic lesions masquerading the abscesses and also wide-spread multiple distant invasions of a squamous cell lung carcinoma in a short time period.

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

PubMed Central

Cooney, Rachel M; Warren, Bryan F; Altman, Douglas G; Abreu, Maria T; Travis, Simon PL

2007-01-01

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached. PMID:17592647

[Clinical judgment is a schema. Conceptual proposals and training perspectives.

PubMed

Nagels, Marc

2017-06-01

Clinical judgment is a critical concept for the development of nursing and nursing education. Its theoretical origins are multiple and its definition is not yet consensus. The analysis of the scientific and professional literature shows heterogeneous and dispersed points of views, notably on the role of intuition, on its cognitive and metacognitive dimensions, and on its proximity to other concepts. Between professional stakes and epistemological constructions, clinical judgment is still an emerging concept.To overcome the obstacle and contribute to the theoretical effort, we will argue that clinical judgment must be analyzed as a schema. It presents all the characteristics : diagnosis and information necessary for reasoning, rational decision-making process, metacognitive control and evaluation of decision-making. Perspectives then open to better understand the nursing activity.In conclusion, recommendations for developing clinical judgment in training will be presented.

Univariate Analysis of Multivariate Outcomes in Educational Psychology.

ERIC Educational Resources Information Center

Hubble, L. M.

1984-01-01

The author examined the prevalence of multiple operational definitions of outcome constructs and an estimate of the incidence of Type I error rates when univariate procedures were applied to multiple variables in educational psychology. Multiple operational definitions of constructs were advocated and wider use of multivariate analysis was…

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

Clinical case definition for the diagnosis of acute intussusception.

PubMed

Bines, Julie E; Ivanoff, Bernard; Justice, Frances; Mulholland, Kim

2004-11-01

Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.

Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort.

PubMed

Williams, Mitchel T; Tapos, Daniela O; Juhász, Csaba

2014-12-01

Pediatric-onset multiple sclerosis represents around 3-5% of all patients with multiple sclerosis. Both the 2005 and 2010 McDonald criteria for multiple sclerosis have been suggested for the possible use in pediatric-onset multiple sclerosis. Modifications incorporated into the 2010 criteria enabled the fulfillment of dissemination in time to be met with the initial magnetic resonance imaging. The present study was designed to compare the diagnostic sensitivity of these criteria at initial presentation, the time to fulfilling them, and secondary effects of ethnicity in pediatric-onset multiple sclerosis. Twenty-five children with clinically definite multiple sclerosis (mean age, 14.6 ± 3.1 years; 15 girls) from a single center between 2005 and 2012 were analyzed using both the 2005 and 2010 McDonald criteria based on initial clinical presentation and neuroimaging findings comparing diagnostic sensitivity, time interval to meet diagnosis, and ethnicity. Initial multiple sclerosis diagnosis rates applying the 2005 McDonald criteria were 32% compared with 92% for the 2010 criteria (P = 0.0003). The mean time after initial signs until the 2005 and 2010 McDonald criteria for multiple sclerosis were met was 5.0 vs 0.7 months, respectively (P = 0.001). Time to diagnosis using the 2010 criteria was shorter in black children than the European white (P = 0.005). The 2010 McDonald criteria are an appropriate tool for the timely diagnosis of pediatric multiple sclerosis, especially in black children, potentially allowing an earlier initiation of disease-modifying therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Fractured condyle in a 3-month-old infant.

PubMed

Cambell, R L; Moore, R F

1975-07-01

A 3-month-old infant sustained trauma to the mandibular symphysis resulting in radiographic evidence of a fracture of the right condylar head. This presented the diffculty of performing a clinical examination and total reliance on history of a trauma and subsequent swelling. Multiple radiographs of the condyles were used to establish the diagnosis and rule out a film artifact. No definitive treatment was required other than muscle exercises and parental instruction as to potential problems.

Brown-Sequard Syndrome

MedlinePlus

... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. × Definition Brown-Sequard syndrome (BSS) is a rare ... infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. View Full Definition Treatment Generally treatment for individuals ...

Taylor spatial frame fixation in patients with multiple traumatic injuries: study of 57 long-bone fractures.

PubMed

Sala, Francesco; Elbatrawy, Yasser; Thabet, Ahmed M; Zayed, Mahmoud; Capitani, Dario

2013-08-01

To evaluate the Taylor spatial frame (TSF) for primary and definitive fixation of lower limb long-bone fractures in patients with multiple traumatic injuries. Retrospective. Level I trauma center. Consecutive series of 52 patients, 57 fractures (25 femoral and 32 tibial), treated between 2005 and 2009. Forty-nine fractures (86%) were open. Injury Severity Score ≥16 for all patients. Fifty-four fractures (95%) underwent definitive fixation with the TSF and 3 were treated primarily within 48 hours of injury. In 22 cases (39%), fractures were acutely reduced with the TSF, fixed to bone and the struts in sliding mode without further adjustment, and in 35 cases (61%), the total residual deformity correction program was undertaken. Clinical and radiological. Complete union was obtained in 52 fractures (91%) without additional surgery at an average of 29 weeks. Four nonunions and 1 delayed union occurred. Results based on Association for the Study and Application of the Method of Ilizarov criteria: 74% excellent, 16% good, 4% fair, and 7% poor for bone outcomes and 35% excellent, 47% good, and 18% fair for functional outcomes. Eighty-eight percent of patients returned to preinjury work activities. Primary and definitive fixation with the TSF is effective. Advantages include continuity of device until union, reduced risk of infection, early mobilization, restoration of primary defect caused by bone loss, easy and accurate application, convertibility and versatility compared with a monolateral fixator, and improved union rate and range of motion for lower extremity long-bone fractures in patients with multiple traumatic injuries.

Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study.

PubMed

Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil W; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Hicking, Christine; Vermersch, Patrick

2018-04-01

In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Sponsorship in non-commercial clinical trials: definitions, challenges and the role of Good Clinical Practices guidelines.

PubMed

Ravinetto, Raffaella; De Nys, Katelijne; Boelaert, Marleen; Diro, Ermias; Meintjes, Graeme; Adoke, Yeka; Tagbor, Harry; Casteels, Minne

2015-12-30

Non-commercial clinical research plays an increasingly essential role for global health. Multiple partners join in international consortia that operate under the limited timeframe of a specific funding period. One organisation (the sponsor) designs and carries out the trial in collaboration with research partners, and is ultimately responsible for the trial's scientific, ethical, regulatory and legal aspects, while another organization, generally in the North (the funder), provides the external funding and sets funding conditions. Even if external funding mechanisms are key for most non-commercial research, the dependence on an external funder's policies may heavily influence the choices of a sponsor. In addition, the competition for accessing the available external funds is great, and non-commercial sponsors may not be in a position to discuss or refuse standard conditions set by a funder. To see whether the current definitions adequately address the intricacies of sponsorship in externally-funded trials, we looked at how a "sponsor" of clinical trials is defined in selected international guidelines, with particular focus on international Good Clinical Practices codes, and in selected European and African regulations/legislations. Our limited analysis suggests that the sponsors definition from the 1995 WHO Good Clinical Practices code has been integrated as such into many legislations, guidelines and regulations, and that it is not adequate to cover today's reality of funding arrangements in global health, where the legal responsibility and the funding source are de facto split. In agreement with other groups, we suggest that the international Good Clinical Practices codes should be updated to reflect the reality of non-commercial clinical research. In particular, they should explicitly include the distinction between commercial and non-commercial sponsors, and provide guidance to non-commercial sponsors for negotiating with external funding agencies and other research counterparts. Non-commercial sponsors of clinical trials should surely invest in the development of adequate legal, administrative and management skills. By acknowledging their role and specificities, and by providing them with adapted guidance, the international Good Clinical Practices codes would provide valuable guidance and support to non-commercial clinical research, whose relevance for global health is increasingly evident.

The optimal definition of contrast-induced acute kidney injury for prediction of inpatient mortality in patients undergoing percutaneous coronary interventions.

PubMed

Parsh, Jessica; Seth, Milan; Briguori, Carlo; Grossman, Paul; Solomon, Richard; Gurm, Hitinder S

2016-05-01

It is unknown which definition of contrast-induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions is best associated with inpatient mortality and whether this association is stable across patients with various preprocedural serum creatinine (SCr) values. We applied logistic regression models to multiple CI-AKI definitions used by the Kidney Disease Improving Global Outcomes guidelines and previously published studies to examine the impact of preprocedural SCr on a candidate definition's correlation with the adverse outcome of inpatient mortality. We used likelihood ratio tests to examine candidate definitions and identify those where association with inpatient mortality remained constant regardless of preprocedural SCr. These definitions were assessed for specificity, sensitivity, and positive and negative predictive values to identify an optimal definition. Our study cohort included 119,554 patients who underwent percutaneous coronary intervention in Michigan between 2010 and 2014. Most commonly used definitions were not associated with inpatient mortality in a constant fashion across various preprocedural SCr values. Of the 266 candidate definitions examined, 16 definition's association with inpatient mortality was not significantly altered by preprocedural SCr. Contrast-induced acute kidney injury defined as an absolute increase of SCr ≥0.3 mg/dL and a relative SCr increase ≥50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for inpatient mortality. We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥0.3 mg/dL and a relative SCr increase ≥50%. Further work is needed to validate this definition in independent studies and to establish its utility for clinical trials and quality improvement efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

Spontaneous hemothorax caused by ruptured multiple mycotic aortic aneurysms: a case report and literature review.

PubMed

Li, Po-Sung; Tsai, Chung-Lin; Hu, Sung-Yuan; Lin, Tzu-Chieh; Chang, Yao-Tien

2017-12-02

Mycotic aortic aneurysm (MAA) is a rare clinical entity with an incidence of 1-3%, but it is a life-threatening infection of aorta characterized by dilatation of aorta with false lumen. Multiple MAAs have been reported rarely with an incidence of 0.03% and associated with a high mortality rate of 80% if ruptured. A hypertensive and diabetic 78-year-old man visited our emergency department complaining intermittent dull and tingled pain over the left flank region for 1 week. Chest X-ray showed left pleural effusion and hemothorax was confirmed by thoracocentesis. Computed tomography (CT) of chest demonstrated multiple thoracic aortic aneurysms and the pathological findings disclosed the diagnosis of multiple MAAs. He was discharged under an uneventful condition post-surgical aortic repair with adequate intravenous antibiotics for 4 weeks. CT scan may make a definite diagnosis of multiple MAAs and management with surgical debridement, aortic repair and full-course antibiotics for Gram-positive coccus and/or Gram-negative bacillus is recommended.

Connected health and multiple sclerosis.

PubMed

Cohen, M

2018-06-01

There is as yet no consensual definition of "connected health". In general, the term refers to the growing use of technology and, in particular, mobile technology in medicine. Over the past 10 years, there have been an increasing number of published reports on the wide-ranging and heterogeneous fields involving the application of technology in medicine, ranging from telemedicine to tools to improve patients' evaluation and monitoring by physicians, as well as a multitude of patient-centered applications. They also represent promising tools in the field of clinical research. This report is a review of the importance of using this technology in the management of multiple sclerosis patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

PubMed

Aggarwal, Rohit; Rider, Lisa G; Ruperto, Nicolino; Bayat, Nastaran; Erman, Brian; Feldman, Brian M; Oddis, Chester V; Amato, Anthony A; Chinoy, Hector; Cooper, Robert G; Dastmalchi, Maryam; Fiorentino, David; Isenberg, David; Katz, James D; Mammen, Andrew; de Visser, Marianne; Ytterberg, Steven R; Lundberg, Ingrid E; Chung, Lorinda; Danko, Katalin; García-De la Torre, Ignacio; Song, Yeong Wook; Villa, Luca; Rinaldi, Mariangela; Rockette, Howard; Lachenbruch, Peter A; Miller, Frederick W; Vencovsky, Jiri

2017-05-01

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute percent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (P < 0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement. © 2017, American College of Rheumatology.

Dupuytren disease: on our way to a cure?

PubMed

Degreef, Ilse; De Smet, Luc

2013-06-01

Despite its high prevalence, the clinical presentation and severity of Dupuytren disease is extremely variable. The disease features a broad spectrum of symptoms, from simple nodules without the slightest clinical impact towards an extremely disabling form requiring multiple surgical procedures, sometimes even partial hand amputations. Recurrence after surgery is considered a failure for both patient and surgeon, but its definition is vague. The term 'recontracture' was coined by a patient and reflects the disappointment of recurrent disease. Wether or not a treatment option will insure a definite result, may depend more on the severity of the disease, which is patient specific, than on the treatment method itself. If a patient presents with Dupuytren disease, one should not merely evaluate his hands. Different clinical and personal history features may uncover a severe fibrosis diathesis and both correct information to the patient and an individualized treatment plan are needed. In the near future, a simple genetic test may help to identify patients at risk. Similar to the evolving knowledge and treatment modalities seen in rheumatoid arthritis, treatment of Dupuytren disease is likely to advance in the direction of disease control with pharmacotherapy and single shot minimal invasive enzymatic fasciotomy with collagenase to correct established contractures.

Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

PubMed

Voortman, Margarete M; Stojakovic, Tatjana; Pirpamer, Lukas; Jehna, Margit; Langkammer, Christian; Scharnagl, Hubert; Reindl, Markus; Ropele, Stefan; Seifert-Held, Thomas; Archelos, Juan-Jose; Fuchs, Siegrid; Enzinger, Christian; Fazekas, Franz; Khalil, Michael

2017-10-01

Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

Familial risks of breast and prostate cancers: does the definition of the at risk period matter?

PubMed

Brandt, Andreas; Bermejo, Justo Lorenzo; Sundquist, Jan; Hemminki, Kari

2010-03-01

'Being at familial risk' may have different connotations in studies on familial risk of cancer. The register-based definition of a family history considers individuals with an affected relative at familial risk independently of the family member's diagnostic time. Alternatively, the individuals are classified to be at familial risk only after the diagnosis date of their relative, relevant to clinical counselling and screening situations. The aim of this study was to compare familial breast and prostate cancer risks according to the two definitions. The nationwide Swedish Family-Cancer Database with information on cancers from 1958 to 2006 was used to calculate the hazard ratio of breast and prostate cancers according to family history using Cox regression. Family history was defined considering the number and type of affected relatives and the relative's diagnostic age, respectively. Individuals were considered at familial risk from their entry to the study or, alternatively, from the diagnostic time of the relative. Hazard ratios were equal whether individuals were considered at risk independent of the relative's diagnostic date or only after the relative's diagnostic date. These results indicate that studies on familial breast or prostate cancer risk which do not take the relative's diagnosis date into account are applicable to screening and clinical counselling situations. The estimates according to the register-based definition are based on larger numbers of patients, which may be crucial for analysis of small groups such as families of multiple cases. Copyright 2009 Elsevier Ltd. All rights reserved.

Quantitative assessment of upper extremities motor function in multiple sclerosis.

PubMed

Daunoraviciene, Kristina; Ziziene, Jurgita; Griskevicius, Julius; Pauk, Jolanta; Ovcinikova, Agne; Kizlaitiene, Rasa; Kaubrys, Gintaras

2018-05-18

Upper extremity (UE) motor function deficits are commonly noted in multiple sclerosis (MS) patients and assessing it is challenging because of the lack of consensus regarding its definition. Instrumented biomechanical analysis of upper extremity movements can quantify coordination with different spatiotemporal measures and facilitate disability rating in MS patients. To identify objective quantitative parameters for more accurate evaluation of UE disability and relate it to existing clinical scores. Thirty-four MS patients and 24 healthy controls (CG) performed a finger-to-nose test as fast as possible and, in addition, clinical evaluation kinematic parameters of UE were measured by using inertial sensors. Generally, a higher disability score was associated with an increase of several temporal parameters, like slower task performance. The time taken to touch their nose was longer when the task was fulfilled with eyes closed. Time to peak angular velocity significantly changed in MS patients (EDSS > 5.0). The inter-joint coordination significantly decreases in MS patients (EDSS 3.0-5.5). Spatial parameters indicated that maximal ROM changes were in elbow flexion. Our findings have revealed that spatiotemporal parameters are related to the UE motor function and MS disability level. Moreover, they facilitate clinical rating by supporting clinical decisions with quantitative data.

Pulmonary function and dysfunction in multiple sclerosis.

PubMed

Smeltzer, S C; Utell, M J; Rudick, R A; Herndon, R M

1988-11-01

Pulmonary function was studied in 25 patients with clinically definite multiple sclerosis with a range of motor impairment. Forced vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted; FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively). Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and expiratory muscle weakness occurred most frequently. These findings demonstrate that marked expiratory weakness develops in severely paraparetic patients with multiple sclerosis and the weakness increases as the upper extremities become increasingly involved.

Self-Efficacy as a Predictor of Self-Reported Physical, Cognitive and Social Functioning in Multiple Sclerosis

PubMed Central

Schmitt, Margaret M.; Goverover, Yael; DeLuca, John; Chiaravalloti, Nancy

2014-01-01

Objective Investigate whether self-efficacy is associated with physical, cognitive and social functioning in individuals with Multiple Sclerosis (MS) when controlling for disease-related characteristics and depressive symptomatology. Participants 81 individuals between the ages of 29 and 67 with a diagnosis of clinically definite MS. Method Hierarchical regression analysis was employed to examine the relationships between self-efficacy and self-reported physical, cognitive, and social functioning. Results Self-efficacy is a significant predictor of self-reported physical, cognitive and social functioning in MS after controlling for variance due to disease related factors and depressive symptomatology. Conclusions Self-efficacy plays a significant role in individual adjustment to MS across multiple areas of functional outcome, beyond that which is accounted for by disease related variables and symptoms of depression. PMID:24320946

The use of gaming technology for rehabilitation in people with multiple sclerosis.

PubMed

Taylor, M J D; Griffin, M

2015-04-01

Gaming technology - exergaming - is a novel tool to facilitate exercise, improve balance, and encourage rehabilitation training. This review will describe some of the key exergame research to promote physical activity and its use in rehabilitation in other diseases or clinical populations. We will then describe the current state of research in exergaming in people with multiple sclerosis and describe the theories for the mechanism behind some of the improvements in outcomes seen after using exergaming. Lastly, we will identify gaps in the literature and provide directions for future work in this growing area. The current work is contradictory and there is no consensus with regards to training duration/intensity and the outcomes used to assess the clinical effectiveness. This in part is due to the off-the-shelf nature of the games used. A more satisfactory approach would be the development of bespoke games which match a clinical need. Exergames are seen as enjoyable and could be effective in enhancing adherence to rehabilitation. However, the definitive RCT has yet to be carried out comparing exergaming to traditional exercise. © The Author(s), 2014.

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

PubMed

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Person-Centered Care: A Definition and Essential Elements.

PubMed

2016-01-01

Improving healthcare safety, quality, and coordination, as well as quality of life, are important aims of caring for older adults with multiple chronic conditions and/or functional limitations. Person-centered care is an approach to meeting these aims, but there are no standardized, agreed-upon parameters for delivering such care. The SCAN Foundation charged a team from the American Geriatrics Society (AGS) in collaboration with a research and clinical team from the Keck School of Medicine of the University of Southern California to provide the evidence base to support a definition of person-centered care and its essential elements. An interprofessional panel of experts in person-centered care principles and practices that the AGS convened developed this statement. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Management Approaches for Enterocutaneous Fistulas.

PubMed

Heimroth, Jamie; Chen, Eric; Sutton, Erica

2018-03-01

There are very few clinical studies that highlight a definitive and comprehensive guideline for the management of enterocutaneous fistulas. Most accepted guidelines are found in textbooks and are taken from expert advice and case reports. The goal of this review is to highlight advancements relevant to the management of enterocutaneous fistulas from the recent two to three years. Although strong evidence-based guidelines are lacking, the consensus is that a multidisciplinary team working with a clear treatment plan targeting multiple aspects of management can maximize patient outcomes.

A case of acute generalized exanthematous pustulosis due to amoxicillin-clavulanate with multiple positivity to beta-lactam patch testing.

PubMed

Bomarrito, L; Zisa, G; Delrosso, G; Farinelli, P; Galimberti, M

2013-09-01

We present a case of acute generalized exanthematous pustolosis (AGEP) induced by amoxicillin-clavulanate. Clinical diagnosis was confirmed by symptoms presentation and  histological features (Euroscar score point compatible with definite diagnosis). Patch testing performer six months later confirmed sensitization to the culprit drug and showed positivity also to other beta-lactam antibiotics (penicillin G and cephalexin). We believe that a T cell delayed response to betalactams common ring could be involved.

Randomized, controlled, two-arm, interventional, multicenter study on risk-adapted damage control orthopedic surgery of femur shaft fractures in multiple-trauma patients.

PubMed

Rixen, Dieter; Steinhausen, Eva; Sauerland, Stefan; Lefering, Rolf; Maegele, Marc G; Bouillon, Bertil; Grass, Guido; Neugebauer, Edmund A M

2016-01-25

Long bone fractures, particularly of the femur, are common in multiple-trauma patients, but their optimal management has not yet been determined. Although a trend exists toward the concept of "damage control orthopedics" (DCO), current literature is inconclusive. Thus, a need exists for a more specific controlled clinical study. The primary objective of this study was to clarify whether a risk-adapted procedure for treating femoral fractures, as opposed to an early definitive treatment strategy, leads to an improved outcome (morbidity and mortality). The study was designed as a randomized controlled multicenter study. Multiple-trauma patients with femur shaft fractures and a calculated probability of death of 20 to 60 % were randomized to either temporary fracture fixation with external fixation and defined secondary definitive treatment (DCO) or primary reamed nailing (early total care). The primary objective was to reduce the extent of organ failure as measured by the maximum sepsis-related organ failure assessment (SOFA) score. Thirty-four patients were randomized to two groups of 17 patients each. Both groups were comparable regarding sex, age, injury severity score, Glasgow Coma Scale, prothrombin time, base excess, calculated probability of death, and other physiologic variables. The maximum SOFA score was comparable (nonsignificant) between the groups. Regarding the secondary endpoints, the patients with external fixation required a significantly longer ventilation period (p = 0.049) and stayed on the intensive care significantly longer (p = 0.037), whereas the in-hospital length of stay was balanced for both groups. Unfortunately, the study had to be terminated prior to reaching the anticipated sample size because of unexpected low patient recruitment. Thus, the results of this randomized study reflect the ambivalence in the literature. No advantage of the damage control concept could be detected in the treatment of femur fractures in multiple-trauma patients. The necessity for scientific evaluation of this clinically relevant question remains. Current Controlled Trials ISRCTN10321620 Date assigned: 9 February 2007.

Drawing Boundaries: The Difficulty in Defining Clinical Reasoning.

PubMed

Young, Meredith; Thomas, Aliki; Lubarsky, Stuart; Ballard, Tiffany; Gordon, David; Gruppen, Larry D; Holmboe, Eric; Ratcliffe, Temple; Rencic, Joe; Schuwirth, Lambert; Durning, Steven J

2018-01-23

Clinical reasoning is an essential component of a health professional's practice. Yet clinical reasoning research has produced a notably fragmented body of literature. In this article, the authors describe the pause-and-reflect exercise they undertook during the execution of a synthesis of the literature on clinical reasoning in the health professions. Confronted with the challenge of establishing a shared understanding of the nature and relevant components of clinical reasoning, members of the review team paused to independently generate their own personal definitions and conceptualizations of the construct. Here, the authors describe the variability of definitions and conceptualizations of clinical reasoning present within their own team. Drawing on an analogy from mathematics, they hypothesize that the presence of differing "boundary conditions" could help explain individuals' differing conceptualizations of clinical reasoning and the fragmentation at play in the wider sphere of research on clinical reasoning. Specifically, boundary conditions refer to the practice of describing the conditions under which a given theory is expected to hold, or expected to have explanatory power. Given multiple theoretical frameworks, research methodologies, and assessment approaches contained within the clinical reasoning literature, different boundary conditions are likely at play. Open acknowledgment of different boundary conditions and explicit description of the conceptualization of clinical reasoning being adopted within a given study would improve research communication, support comprehensive approaches to teaching and assessing clinical reasoning, and perhaps encourage new collaborative partnerships among researchers who adopt different boundary conditions.Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

An empirical definition of clinical supervision.

PubMed

Milne, Derek

2007-11-01

The growing recognition of clinical supervision as the basis for high-quality mental health services is apparent in policy, research and clinical practice, but an empirical definition is required to progress research and practice. A logical analysis was used to draft a working definition, and then a systematic review of 24 empirical studies of clinical supervision produced a best evidence synthesis, which was used to test and improve this definition. The logical analysis indicated that the most popular definition (Bernard & Goodyear, 1992) failed all four necessary tests of a good definition: precision, specification, operationalization and corroboration. The systematic review synthesis was then used to test the working definition, which passed these tests (with two amendments). These two complementary review approaches created a firmer basis for advancing research and practice.

A Conceptual and Empirical Review of the Meaning, Measurement, Development, and Teaching of Intervention Competence in Clinical Psychology

PubMed Central

Barber, Jacques P.

2009-01-01

Through the course of this paper we discuss several fundamental issues related to the intervention competence of psychologists. Following definitional clarification and proposals for more strictly distinguishing competence from adherence, we interpret Dreyfus and Dreyfus’s (1986) five stage theory of competence development (from novice to expert) within a strictly clinical framework. Existing methods of competence assessment are then evaluated, and we argue for the use of new and multiple assessment modalities. Next, we utilize the previous sections as a foundation to propose methods for training and evaluating competent psychologists. Lastly, we discuss several potential impediments to large scale competence assessment and education, such as the heterogeneity of therapeutic orientations and what could be termed a lack of transparency in clinical training. PMID:18952334

Racial and ethnic disparity in food allergy in the United States: a systematic review.

PubMed

Greenhawt, Matthew; Weiss, Christopher; Conte, Marisa L; Doucet, Marlie; Engler, Amy; Camargo, Carlos A

2013-01-01

The prevalence of food allergy is rising among US children. Little is known about racial/ethnic disparities in food allergy. We performed a systematic literature review to understand racial/ethnic disparities in food allergy in the United States. We searched PubMed/MEDLINE, Embase, and Scopus for original data about racial/ethnic disparities in the diagnosis, prevalence, treatment, or clinical course of food allergy or sensitization, with a particular focus on black (African American) race. Articles were analyzed by study methodology, racial/ethnic composition, food allergy definition, outcomes, summary statistic used, and covariate adjustment. Twenty of 645 identified articles met inclusion criteria. The studies used multiple differing criteria to define food allergy, including self-report, sensitization assessed by serum food-specific IgE to selected foods without corroborating history, discharge codes, clinic chart review, and event-reporting databases. None used oral food challenge. In 12 studies, black persons (primarily children) had significantly increased adjusted odds of food sensitization or significantly higher proportion or odds of food allergy by self-report, discharge codes, or clinic-based chart review than white children. Major differences in study methodology and reporting precluded calculation of a pooled estimate of effect. Sparse and methodologically limited data exist about racial/ethnic disparity in food allergy in the United States. Available data lack a common definition for food allergy and use indirect measures of allergy, not food challenge. Although data suggest an increased risk of food sensitization, self-reported allergy, or clinic-based diagnosis of food allergy among black children, no definitive racial/ethnic disparity could be found among currently available studies. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Measuring Racial/Ethnic Disparities in Health Care: Methods and Practical Issues

PubMed Central

Cook, Benjamin Lê; McGuire, Thomas G; Zaslavsky,, Alan M

2012-01-01

Objective To review methods of measuring racial/ethnic health care disparities. Study Design Identification and tracking of racial/ethnic disparities in health care will be advanced by application of a consistent definition and reliable empirical methods. We have proposed a definition of racial/ethnic health care disparities based in the Institute of Medicine's (IOM) Unequal Treatment report, which defines disparities as all differences except those due to clinical need and preferences. After briefly summarizing the strengths and critiques of this definition, we review methods that have been used to implement it. We discuss practical issues that arise during implementation and expand these methods to identify sources of disparities. We also situate the focus on methods to measure racial/ethnic health care disparities (an endeavor predominant in the United States) within a larger international literature in health outcomes and health care inequality. Empirical Application We compare different methods of implementing the IOM definition on measurement of disparities in any use of mental health care and mental health care expenditures using the 2004–2008 Medical Expenditure Panel Survey. Conclusion Disparities analysts should be aware of multiple methods available to measure disparities and their differing assumptions. We prefer a method concordant with the IOM definition. PMID:22353147

The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After.

PubMed

Bassi, Claudio; Marchegiani, Giovanni; Dervenis, Christos; Sarr, Micheal; Abu Hilal, Mohammad; Adham, Mustapha; Allen, Peter; Andersson, Roland; Asbun, Horacio J; Besselink, Marc G; Conlon, Kevin; Del Chiaro, Marco; Falconi, Massimo; Fernandez-Cruz, Laureano; Fernandez-Del Castillo, Carlos; Fingerhut, Abe; Friess, Helmut; Gouma, Dirk J; Hackert, Thilo; Izbicki, Jakob; Lillemoe, Keith D; Neoptolemos, John P; Olah, Attila; Schulick, Richard; Shrikhande, Shailesh V; Takada, Tadahiro; Takaori, Kyoichi; Traverso, William; Vollmer, Charles R; Wolfgang, Christopher L; Yeo, Charles J; Salvia, Roberto; Buchler, Marcus

2017-03-01

In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former "grade A postoperative pancreatic fistula" is now redefined and called a "biochemical leak," because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Minimal Clinically Important Difference: A Review of Outcome Measure Score Interpretation.

PubMed

Engel, Lisa; Beaton, Dorcas E; Touma, Zahi

2018-05-01

Clinicians, researchers, and outcome stakeholders have the crucial, albeit difficult, task of quantifying when a person or group experiences important change or difference on any given outcome measure, often in response to a specific intervention. The minimal clinically important difference (MCID) provides this quantified value of change/difference for a measure. There are many methods for MCID derivation, which can result in multiple values for the same measure. Thus, it is important for potential users of MCID values to be aware of the nuances of MCID development and cautions for interpreting values. This review outlines MCID-related definitions, methods, and guidelines. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

PubMed

Runde, Joseph; Rivera-Rivera, Edgardo; Pompeii-Wolfe, Cecelia; Clardy, Christopher; Sentongo, Timothy

2018-05-10

Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome. © 2018 American Society for Parenteral and Enteral Nutrition.

The metabolic syndrome: validity and utility of clinical definitions for cardiovascular disease and diabetes risk prediction.

PubMed

Cameron, Adrian

2010-02-01

The purpose of clinical definitions of the metabolic syndrome is frequently misunderstood. While the metabolic syndrome as a physiological process describes a clustering of numerous age-related metabolic abnormalities that together increase the risk for cardiovascular disease and type 2 diabetes, clinical definitions include obesity which is thought to be a cause rather than a consequence of metabolic disturbance, and several elements that are routinely measured in clinical practice, including high blood pressure, high blood glucose and dyslipidaemia. Obesity is frequently a central player in the development of the metabolic syndrome and should be considered a key component of clinical definitions. Previous clinical definitions have differed in the priority given to obesity. Perhaps more importantly than its role in a clinical definition, however, is obesity in isolation before the hallmarks of metabolic dysfunction that typify the syndrome have developed. This should be treated seriously as an opportunity to prevent the consequences of the global diabetes epidemic now apparent. Clinical definitions were designed to identify a population at high lifetime CVD and type 2 diabetes risk, but in the absence of several major risk factors for each condition, are not optimal risk prediction devices for either. Despite this, the metabolic syndrome has several properties that make it a useful construct, in conjunction with short-term risk prediction algorithms and sound clinical judgement, for the identification of those at high lifetime risk of CVD and diabetes. A recently published consensus definition provides some much needed clarity about what a clinical definition entails. Even this, however, remains a work in progress until more evidence becomes available, particularly in the area of ethnicity-specific waist cut-points. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Relevance of individual participant data meta-analysis for studies in obstetrics: delivery versus expectant monitoring for hypertensive disorders of pregnancy.

PubMed

Broekhuijsen, Kim; Bernardes, Thomas; van Baaren, Gert-Jan; Tajik, Parvin; Novikova, Natalia; Thangaratinam, Shakila; Boers, Kim; Koopmans, Corine M; Wallace, Kedra; Shennan, Andrew H; Langenveld, Josje; Groen, Henk; van den Berg, Paul P; Mol, Ben Willem J; Franssen, Maureen T M

2015-08-01

Like many other research subjects in obstetrics, research on immediate delivery versus expectant monitoring for women with hypertensive disorders of pregnancy faces certain challenges when it comes to interpretation and generalisation of the results; relatively rare outcomes are studied, in a clinically heterogeneous population, while the clinical practice in some countries has dictated that studies in term pregnancy were completed before earlier gestational ages could be studied. This has resulted in multiple smaller studies, some studying surrogate outcome measures, with different in- and exclusion criteria, and without enough power for reliable subgroup analyses. All this complicates the generation of definitive answers and implementation of the results into clinical practice. Performing multiple studies and subsequently pooling their results in a meta-analysis can be a way to overcome the difficulties of studying relatively rare outcomes and subgroups with enough power, as well as a solution to reach a final answer on questions involving an uncertain and possibly harmful intervention. However, in the case of the current studies on delivery versus expectant monitoring in women with hypertensive disorders of pregnancy, differences regarding eligibility criteria, outcome measures and subgroup definitions make it difficult to pool their results in an aggregate meta-analysis. Individual patient data meta-analysis (IPDMA) has the potential to overcome these challenges, because it allows for flexibility regarding the choice of endpoints and standardisation of inclusion and exclusion criteria across studies. In addition, it has more statistical power for informative subgroup analyses. We therefore propose an IPDMA on immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy, and advocate the use of IPDMA for research questions in obstetrics that face similar challenges. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

PubMed

Leigh, Margaret W; Ferkol, Thomas W; Davis, Stephanie D; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D; Sagel, Scott D; Milla, Carlos; Olivier, Kenneth N; Sullivan, Kelli M; Zariwala, Maimoona A; Pittman, Jessica E; Shapiro, Adam J; Carson, Johnny L; Krischer, Jeffrey; Hazucha, Milan J; Knowles, Michael R

2016-08-01

Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as "definite PCD" (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), "probable/possible PCD" (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and "other diagnosis or undefined." Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. From 534 participants 18 years of age and younger, 205 were identified as having "definite PCD" (including 164 with two mutations in a PCD-associated gene), 187 were categorized as "other diagnosis or undefined," and 142 were defined as having "probable/possible PCD." Participants with "definite PCD" were compared with the "other diagnosis or undefined" group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167).

Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

PubMed

Berrut, G; Andrieu, S; Araujo de Carvalho, I; Baeyens, J P; Bergman, H; Cassim, B; Cerreta, F; Cesari, M; Cha, H B; Chen, L K; Cherubini, A; Chou, M Y; Cruz-Jentoft, A J; De Decker, L; Du, P; Forette, B; Forette, F; Franco, A; Guimaraes, R; Guttierrez-Robledo, L M; Jauregui, J; Khavinson, V; Lee, W J; Peng, L N; Perret-Guillaume, C; Petrovic, M; Retornaz, F; Rockwood, K; Rodriguez-Manas, L; Sieber, C; Spatharakis, G; Theou, O; Topinkova, E; Vellas, B; Benetos, A

2013-01-01

Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

Skin Cancer of the Head and Neck With Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluck, Iris; Ibrahim, Mohannad; Popovtzer, Aron

2009-05-01

Purpose: To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Methods and Materials: Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Results: Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure patternmore » was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Conclusions: Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.« less

Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management

PubMed Central

Kristinsson, Sigurdur Y; Minter, Alex R; Korde, Neha; Tan, Esther; Landgren, Ola

2011-01-01

The manifestations of bone involvement in patients with multiple myeloma (MM) can have devastating clinical effects and increase mortality. Recent studies demonstrate that patients with the precursor conditions smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS) show evidence of bone disease and increased risk of fractures. The understanding of the pathogenesis of bone disease in MM has expanded in recent years. The traditional skeletal survey will probably be replaced by newer and more sensitive imaging techniques, which may have a prognostic impact and change our definition of MGUS and SMM. Bisphosphonates are recommended to prevent skeletal events in patients with MM, and have also been studied in SMM and MGUS. This article summarizes the current knowledge of bone disease in plasma cell disorders, and discusses the current standard and future role of novel imaging techniques, as well as the evidence and current guidelines for bisphosphonates in MM, SMM and MGUS. PMID:21745013

Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations.

PubMed

Milone, Margherita; Brunetti-Pierri, Nicola; Tang, Lin-Ya; Kumar, Neeraj; Mezei, Michelle M; Josephs, Keith; Powell, Suzanne; Simpson, Ericka; Wong, Lee-Jun C

2008-08-01

Mutations in POLG gene are responsible for a wide spectrum of clinical disorders with altered mitochondrial DNA (mtDNA) integrity, including mtDNA multiple deletions and depletion. Sensory ataxic neuropathy with ophthalmoparesis (SANDO) caused by mutations in POLG gene, fulfilling the clinical triad of sensory ataxic neuropathy, dysarthria and/or dysphagia and ophthalmoparesis, has described in a few reports. Here we described five cases of adult onset autosomal recessive sensory ataxic neuropathy with ophthalmoplegia. All patients had ataxia, neuropathy, myopathy, and progressive external ophthalmoplegia (PEO). The muscle pathology revealed ragged-red and cytochrome c oxidase (COX) negative fibers in three patients. However, deficiencies in the activities of mitochondrial respiratory chain enzyme complexes were not detected in any of the patients' muscle samples. Multiple deletions of mtDNA were detected in blood and muscle specimens but mtDNA depletion was not found. Due to these diagnostic difficulties, POLG-related syndromes are definitively diagnosed based on the presence of deleterious mutations in the POLG gene.

The effectiveness of music as a mnemonic device on recognition memory for people with multiple sclerosis.

PubMed

Moore, Kimberly Sena; Peterson, David A; O'Shea, Geoffrey; McIntosh, Gerald C; Thaut, Michael H

2008-01-01

Research shows that people with multiple sclerosis exhibit learning and memory difficulties and that music can be used successfully as a mnemonic device to aid in learning and memory. However, there is currently no research investigating the effectiveness of music mnemonics as a compensatory learning strategy for people with multiple sclerosis. Participants with clinically definitive multiple sclerosis (N = 38) were given a verbal learning and memory test. Results from a recognition memory task were analyzed that compared learning through music (n = 20) versus learning through speech (n = 18). Preliminary baseline neuropsychological data were collected that measured executive functioning skills, learning and memory abilities, sustained attention, and level of disability. An independent samples t test showed no significant difference between groups on baseline neuropsychological functioning or on recognition task measures. Correlation analyses suggest that music mnemonics may facilitate learning for people who are less impaired by the disease. Implications for future research are discussed.

Intermittent catheterisation for long-term bladder management (abridged cochrane review).

PubMed

Prieto, Jacqui A; Murphy, Catherine; Moore, Katherine N; Fader, Mandy J

2015-09-01

To review the evidence on strategies to reduce UTI, other complications or improve satisfaction in intermittent catheter (IC) users by comparing: (1) one catheter design, material or technique versus another; (2) sterile technique versus clean; or (3) single-use (sterile) or multiple-use (clean) catheters. We searched Cochrane Incontinence Group Specialised Trials Register, MEDLINE, EMBASE, CINAHL, ERIC, reference lists, and conference proceedings to November 2013. We contacted other investigators for unpublished data or clarification. Trial screening, assessment and data abstraction were all in accordance with the Cochrane handbook. Thirty one trials (13 RCTs and 18 randomized crossover trials), addressed the inclusion criteria comparing method or design and UTI/bacteriuria, other complications or participant assessed outcomes. Studies varied widely in follow-up, UTI definition and attrition; in some, data could not be combined. Where there were data, confidence intervals were wide and hence clinically important differences could neither be reliably identified nor ruled out. Current research evidence is weak and design issues are significant. It has not yet been established whether incidence of UTI, other complications such as haematuria, or user satisfaction are affected by sterile or clean technique, coated or uncoated catheters, single or multiple-use catheters or by any other strategy. For people using IC, choice of catheter will depend on personal preference, cost, portability, and ease of use. Individuals should discuss the catheter options with their healthcare practitioner. Cost-effectiveness analysis and use of the standard definition of UTI are essential in any proposed clinical trial. © 2015 Wiley Periodicals, Inc.

The Future of Clinical Education: Using the Delphi Technique to Study Allied Health Deans' Perspectives on Definitions and Goals.

PubMed

Romig, Barbara D; Tucker, Ann W; Hewitt, Anne M; O'Sullivan Maillet, Julie

2016-01-01

Allied health (AH) clinical education provides future health professionals with the experiences necessary to develop the healthcare competencies required for success in their individual fields. There is limited information and consensus on the purposes of clinical education, including its definition and goals, and its comprehensive role in AH clinical training. This study explored whether consensus could be achieved in the definition, goals, and factors impacting AH clinical education. An expert panel consisting of 61 AH deans (54.9% of the population) whose institutions were 2013 members of the Association of Schools of Allied Health Professions (ASAHP) participated in a three-round Delphi study. From July 2013 to March 2014, the deans expressed opinions about clinical education and its purposes. Responses were collected, summarized, and refined, and responses were accepted and re-rated until agreement was achieved or the study concluded. The hypothesis that AH deans would agree upon the definition and goals of clinical education was supported by this study's findings. Over 90% of deans "strongly agreed" or "agreed" on the definition of clinical education. A majority (90.2% to 92.7%) agreed with the goals. High agreement was achieved on the purposes of clinical education, resulting in a comprehensive definition of and goals for AH clinical education. The definition and goals of clinical education can be added in the healthcare literature and used in support of AH education.

Application of a simplified definition of diastolic function in severe sepsis and septic shock.

PubMed

Lanspa, Michael J; Gutsche, Andrea R; Wilson, Emily L; Olsen, Troy D; Hirshberg, Eliotte L; Knox, Daniel B; Brown, Samuel M; Grissom, Colin K

2016-08-04

Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis.

PubMed

Wagley, Sariqa; Bokori-Brown, Monika; Morcrette, Helen; Malaspina, Andrea; D'Arcy, Caroline; Gnanapavan, Sharmilee; Lewis, Nicholas; Popoff, Michel R; Raciborska, Dominika; Nicholas, Richard; Turner, Ben; Titball, Richard W

2018-04-01

It was recently reported that, using Western blotting, some multiple sclerosis (MS) patients in the United States had antibodies against epsilon toxin (Etx) from Clostridium perfringens, suggesting that the toxin may play a role in the disease. We investigated for serum antibodies against Etx in UK patients with clinically definite multiple sclerosis (CDMS) or presenting with clinically isolated syndrome (CIS) or optic neuritis (ON) and in age- and gender-matched controls. We tested sera from CDMS, CIS or ON patients or controls by Western blotting. We also tested CDMS sera for reactivity with linear overlapping peptides spanning the amino acid sequence (Pepscan) of Etx. Using Western blotting, 24% of sera in the combined CDMS, CIS and ON groups ( n = 125) reacted with Etx. In the control group ( n = 125), 10% of the samples reacted. Using Pepscan, 33% of sera tested reacted with at least one peptide, whereas in the control group only 16% of sera reacted. Out of 61 samples, 21 (43%) were positive to one or other testing methodology. Three samples were positive by Western blotting and Pepscan. Our results broadly support the previous findings and the role of Etx in the aetiology of MS warrants further investigation.

Dimensional assessment of self- and interpersonal functioning in adolescents: implications for DSM-5's general definition of personality disorder.

PubMed

DeFife, Jared A; Goldberg, Melissa; Westen, Drew

2015-04-01

Central to the proposed DSM-5 general definition of personality disorder (PD) are features of self- and interpersonal functioning. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G) is a coding system that assesses eight dimensions of self- and relational experience that can be applied to narrative data or used by clinically experienced observers to quantify observations of patients in ongoing psychotherapy. This study aims to evaluate the relationship of SCORS-G dimensions to personality pathology in adolescents and their incremental validity for predicting multiple domains of adaptive functioning. A total of 294 randomly sampled doctoral-level clinical psychologists and psychiatrists described an adolescent patient in their care based on all available data. Individual SCORS-G variables demonstrated medium-to-large effect size differences for PD versus non-PD identified adolescents (d = .49-1.05). A summary SCORS-Composite rating was significantly related to composite measurements of global adaptive functioning (r = .66), school functioning (r = .47), externalizing behavior (r = -.49), and prior psychiatric history (r = -.31). The SCORS-Composite significantly predicted variance in domains of adaptive functioning above and beyond age and DSM-IV PD diagnosis (ΔR(2)s = .07-.32). As applied to adolescents, the SCORS-G offers a framework for a clinically meaningful and empirically sound dimensional assessment of self- and other representations and interpersonal functioning capacities. Our findings support the inclusion of self- and interpersonal capacities in the DSM-5 general definition of personality disorder as an improvement to existing PD diagnosis for capturing varied domains of adaptive functioning and psychopathology.

Shin splints--a review of terminology.

PubMed

Batt, M E

1995-01-01

This review is intended to improve the understanding of and rationale for the use of the term shin splints. Currently the term is used widely and variably, with little consensus of definition. Broadly, it denotes the occurrence of exertional lower leg pain; more specifically, it refers to an anatomical site of periostitis. The literature reports a multiplicity of descriptions and definitions of shin splints resultant from the complex etiologies and differing perceptions of these conditions. It is proposed that the term shin splint be recognized as generic, rather than diagnostic, and that specific conditions that currently exist under this term be differentiated. The etiology and interaction of these related conditions are considered, and a classification based on the current literature is given of conditions currently termed shin splints, providing a rationale for their clinical presentations, investigative findings, and interactions.

30 CFR 7.62 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.62 Definitions. The following definitions apply in this subpart: Blasting circuit. A circuit that includes one or more electric...

30 CFR 7.62 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.62 Definitions. The following definitions apply in this subpart: Blasting circuit. A circuit that includes one or more electric...

30 CFR 7.62 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.62 Definitions. The following definitions apply in this subpart: Blasting circuit. A circuit that includes one or more electric...

30 CFR 7.62 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.62 Definitions. The following definitions apply in this subpart: Blasting circuit. A circuit that includes one or more electric...

30 CFR 7.62 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Multiple-Shot Blasting Units § 7.62 Definitions. The following definitions apply in this subpart: Blasting circuit. A circuit that includes one or more electric...

Clinical Definitions of Melioidosis

PubMed Central

Cheng, Allen C.; Currie, Bart J.; Dance, David A. B.; Funnell, Simon G. P.; Limmathurotsakul, Direk; Simpson, Andrew J. H.; Peacock, Sharon J.

2013-01-01

Clinical definitions of melioidosis and inhalation-acquired melioidosis (Burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. Such definitions support accurate public health reporting, preparedness planning for deliberate B. pseudomallei release, design of experimental models, and categorization of naturally acquired melioidosis. PMID:23468355

76 FR 23504 - Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 207 RIN 0750-AH12 Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS Case 2011-D016) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY...

Clinical decision support systems: data quality management and governance.

PubMed

Liaw, Siaw-Teng

2013-01-01

This chapter examines data quality management (DQM) and information governance (IG) of electronic decision support (EDS) systems so that they are safe and fit for use by clinicians and patients and their carers. This is consistent with the ISO definition of data quality as being fit for purpose. The scope of DQM & IG should range from data creation and collection in clinical settings, through cleaning and, where obtained from multiple sources, linkage, storage, use by the EDS logic engine and algorithms, knowledge base and guidance provided, to curation and presentation. It must also include protocols and mechanisms to monitor the safety of EDS, which will feedback into DQM & IG activities. Ultimately, DQM & IG must be integrated across the data cycle to ensure that the EDS systems provide guidance that leads to safe and effective clinical decisions and care.

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

PubMed

Graham, Stephen M; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E; Gale, Marianne; Gie, Robert P; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J; McNeeley, David F; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R; Swaminathan, Soumya; Wingfield, Claire

2012-05-15

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications

PubMed Central

Hamilton, Kristen R.; Littlefield, Andrew K.; Anastasio, Noelle C.; Cunningham, Kathryn A.; Fink, Latham H.; Wing, Victoria C.; Mathias, Charles W.; Lane, Scott D.; Schutz, Christian; Swann, Alan C.; Lejuez, C.W.; Clark, Luke; Moeller, F. Gerard; Potenza, Marc N.

2015-01-01

Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research. PMID:25867840

Difficulties in clinical diagnosis of measles: proposal for modified clinical case definition.

PubMed

Ferson, M J; Young, L C; Robertson, P W; Whybin, L R

1995-10-02

To examine the accuracy of clinical diagnosis of measles and to develop an improved measles clinical case definition. Case survey. Eastern Sydney, December 1990 to August 1993. All cases of measles notified to the Eastern Sydney Public Health Unit without or before serological confirmation. Demographic and clinical details, measles- and rubella-specific IgM and measles complement fixation titres in acute and convalescent (when available) sera and epidemiological links with confirmed measles cases. Of 49 subjects reported and with complete follow-up, 24 were confirmed with measles, four with rubella and 21 had no definite diagnosis. Clinical diagnosis of measles had a false positive rate of 51%. Subjects with confirmed measles were significantly more likely to have a cough (23/24) than those with no definite diagnosis (15/21; P = 0.03) and to be febrile on the day of rash onset (23/24 versus 10/21; P = 0.001). The Centers for Disease Control definition had a sensitivity of 92% but specificity of only 24%. A modified case definition of rash, cough and fever present at onset of rash had equal sensitivity but greater specificity (57%). As measles is no longer common in Australia, clinical diagnosis is unreliable. When a public health response is needed, cases should be confirmed by serological tests or, if not available, we propose use of our modified clinical case definition.

Can we "predict" long-term outcome for ambulatory transcutaneous electrical nerve stimulation in patients with chronic pain?

PubMed

Köke, Albère J; Smeets, Rob J E M; Perez, Roberto S; Kessels, Alphons; Winkens, Bjorn; van Kleef, Maarten; Patijn, Jacob

2015-03-01

Evidence for effectiveness of transcutaneous electrical nerve stimulation (TENS) is still inconclusive. As heterogeneity of chronic pain patients might be an important factor for this lack of efficacy, identifying factors for a successful long-term outcome is of great importance. A prospective study was performed to identify variables with potential predictive value for 2 outcome measures on long term (6 months); (1) continuation of TENS, and (2) a minimally clinical important pain reduction of ≥ 33%. At baseline, a set of risk factors including pain-related variables, psychological factors, and disability was measured. In a multiple logistic regression analysis, higher patient's expectations, neuropathic pain, no severe pain (< 80 mm visual analogue scale [VAS]) were independently related to long-term continuation of TENS. For the outcome "minimally clinical important pain reduction," the multiple logistic regression analysis indicated that no multisited pain (> 2 pain locations) and intermittent pain were positively and independently associated with a minimally clinical important pain reduction of ≥ 33%. The results showed that factors associated with a successful outcome in the long term are dependent on definition of successful outcome. © 2014 World Institute of Pain.

How I treat smoldering multiple myeloma

PubMed Central

Landgren, Ola

2014-01-01

Smoldering myeloma is a heterogeneous clinical entity where a subset of patients has an indolent course of disease that mimics monoclonal gammopathy of undermined significance, whereas others have a more aggressive course that has been described as “early myeloma.” It is defined as either serum M-protein ≥3 g/L or ≥10% monoclonal plasma cells in the bone marrow. There are currently no molecular factors to differentiate risks of progression for these patients. Current recommendations of therapy continue to be patient observation or patient enrollment in clinical trials. However, new definitions of active multiple myeloma recently agreed upon by the International Myeloma Working Group may alter the timing of therapy. On the basis of emerging data of therapy in these patients, it seems reasonable to believe that future recommendations for therapy of patients with smoldering myeloma will become an increasingly important topic. In this article, we review the current knowledge of this disease and risk factors associated with progression. We also examine biological insights and alterations that occur in the tumor clone and the surrounding bone marrow niche. Finally, we review clinical trials that have been performed in these patients and provide recommendations for follow-up of patients with this unique disease entity. PMID:25298034

[Osteoarticular coccidioidomicosis. Clinical and pathological study of 36 Mexican patients].

PubMed

Torres-Nájera, Manuel; de la Garza-Galván, Sergio; Cerda-Flores, Ricardo M; Nocedal-Rustrián, Fausto C; Calderón-Garcidueñas, Ana Laura

2006-01-01

Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1% of cases and one of its manifestation is osteoarthritis. To describe the clinical and pathological characteristics of 36 patients with osteoarthritis by Coccidioides immitis (COA). The surgical pathology records of two medical institutions were reviewed; patients with clinical diagnosis of osteoarthritis and definitive histopathological diagnosis of COA were included in the study. Results were analyzed by contingence tables (RXC) and chi2 test. Twenty six adults (19 men, seven women) and 10 children (seven males, three females) were studied. The chi2 analysis demonstrated a predominance of disease in men (72.2%, p = 0.008). There was no difference between males and females in relation to history of mycotic disease or diagnosis of lung disease after the diagnosis of COA. Bone involvement (76% of cases) was more frequent that pure joint lesions and the predominant radiological lesion was of lytic type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them were men with multiple vertebral bone lesions. The COA was the only manifestation of disease in 83% of the patients. Therefore is important to consider this etiology in patients of endemic area. The clinical and radiological spectrum of COA is wide and may include a dentigerous and synovial cyst or simulates metastatic disease. The recognition of the clinical manifestations of COA may contribute to an opportune diagnosis and treatment.

Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment.

PubMed

Akcali, Aylin; Bal, Berrin; Erbagci, Binnur

2017-07-01

Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

PubMed

Aggarwal, Rohit; Rider, Lisa G; Ruperto, Nicolino; Bayat, Nastaran; Erman, Brian; Feldman, Brian M; Oddis, Chester V; Amato, Anthony A; Chinoy, Hector; Cooper, Robert G; Dastmalchi, Maryam; Fiorentino, David; Isenberg, David; Katz, James D; Mammen, Andrew; de Visser, Marianne; Ytterberg, Steven R; Lundberg, Ingrid E; Chung, Lorinda; Danko, Katalin; García-De la Torre, Ignacio; Song, Yeong Wook; Villa, Luca; Rinaldi, Mariangela; Rockette, Howard; Lachenbruch, Peter A; Miller, Frederick W; Vencovsky, Jiri

2017-05-01

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Redefining Myocardial Infarction: What Is New In The ESC/ACCF/AHA/WHF Third Universal Definition Of Myocardial Infarction?

PubMed Central

Alam, Mahboob; Virani, Salim S.; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations. PMID:24066201

Redefining myocardial infarction: what is new in the ESC/ACCF/AHA/WHF Third Universal Definition of myocardial infarction?

PubMed

Jneid, Hani; Alam, Mahboob; Virani, Salim S; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations.

A Hierarchical Multiple-Level Approach to the Assessment of Interpersonal Relatedness and Self-Definition: Implications for Research, Clinical Practice, and DSM Planning.

PubMed

Luyten, Patrick; Blatt, Sidney J

2016-01-01

Extant research suggests there is considerable overlap between so-called 2-polarities models of personality development; that is, models that propose that personality development evolves through a dialectic synergistic interaction between 2 key developmental tasks across the life span-the development of self-definition on the one hand and of relatedness on the other. These models have attracted considerable research attention and play a central role in DSM planning. This article provides a researcher- and clinician-friendly guide to the assessment of these personality theories. We argue that current theoretical models focus on issues of relatedness and self-definition at different hierarchically organized levels of analysis; that is (a) at the level of broad personality features, (b) at the motivational level (i.e., the motivational processes underlying the development of these dimensions), and (c) at the level of underlying internal working models or cognitive affective schemas, and the specific interpersonal features and problems in which they are expressed. Implications for further research and DSM planning are outlined.

Defining the Field of Behavioral Medicine: A Collaborative Endeavor.

PubMed

Dekker, Joost; Stauder, Adrienne; Penedo, Frank J

2017-02-01

To respond to comments on our proposal for an update of the definition and scope of behavioral medicine. We identify common themes in the comments and provide a response. We discuss the relationship of behavioral medicine to other disciplines and fields, the scope of behavioral medicine, and issues related to the application of behavioral medicine. Based on the comments of our esteemed colleagues and our reflection on those comments, we now offer the following refined definition and scope of behavioral medicine. 'Behavioral medicine can be defined as the field characterized by the collaboration among multiple disciplines concerned with the development and integration of biomedical and behavioral knowledge relevant to health and disease, and the application of this knowledge to prevention, health promotion, diagnosis, treatment, rehabilitation, and care. The scope of behavioral medicine extends from bio-behavioral mechanisms (i.e. the interaction among biomedical, psychological, social, societal, cultural and environmental processes related to health and disease), to clinical diagnosis and intervention, and to public health'. We propose to use this refined definition and scope as the starting point for seeking further input from the ISBM member societies.

Epidemiology of multiple sclerosis in London and Middlesex County, Ontario, Canada.

PubMed

Hader, W J; Elliot, M; Ebers, G C

1988-04-01

A case-controlled epidemiologic study of multiple sclerosis (MS) was carried out in London, Ontario, and its surrounding Middlesex County for the period 1974-1983. The prevalence rates for clinically definite/probable MS on January 1, 1984 were 94/100,000 for the city and 91/100,000 for the county. The estimated annual incidence rate for the decade 1974-83 was 3.4/100,000. The female-to-male sex ratio was 2.5:1. A familial history of MS was recorded in 14.4% of close relatives and a total of 17% when distant relatives are included. The MS group is predominantly of British (70%) and European (23%) origin. The urban-rural residence pattern analysis indicates no significant regional influence on the risk of developing MS.

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality

PubMed Central

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G.; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H.; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

Objective To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. Study design and setting We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Results Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Conclusion Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders’ individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research. PMID:28715491

Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality.

PubMed

von Niederhäusern, Belinda; Schandelmaier, Stefan; Mi Bonde, Marie; Brunner, Nicole; Hemkens, Lars G; Rutquist, Marielle; Bhatnagar, Neera; Guyatt, Gordon H; Pauli-Magnus, Christiane; Briel, Matthias

2017-01-01

To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders' individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research.

The ability of clinical balance measures to identify falls risk in multiple sclerosis: a systematic review and meta-analysis.

PubMed

Quinn, Gillian; Comber, Laura; Galvin, Rose; Coote, Susan

2018-05-01

To determine the ability of clinical measures of balance to distinguish fallers from non-fallers and to determine their predictive validity in identifying those at risk of falls. AMED, CINAHL, Medline, Scopus, PubMed Central and Google Scholar. First search: July 2015. Final search: October 2017. Inclusion criteria were studies of adults with a definite multiple sclerosis diagnosis, a clinical balance assessment and method of falls recording. Data were extracted independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale and the modified Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was conducted for the cross-sectional studies using Review Manager 5. The mean difference with 95% confidence interval in balance outcomes between fallers and non-fallers was used as the mode of analysis. We included 33 studies (19 cross-sectional, 5 randomised controlled trials, 9 prospective) with a total of 3901 participants, of which 1917 (49%) were classified as fallers. The balance measures most commonly reported were the Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale International. Meta-analysis demonstrated fallers perform significantly worse than non-fallers on all measures analysed except the Timed Up and Go Cognitive ( p < 0.05), but discriminative ability of the measures is commonly not reported. Of those reported, the Activities-specific Balance Confidence Scale had the highest area under the receiver operating characteristic curve value (0.92), but without reporting corresponding measures of clinical utility. Clinical measures of balance differ significantly between fallers and non-fallers but have poor predictive ability for falls risk in people with multiple sclerosis.

Clinical trials in "emerging markets": regulatory considerations and other factors.

PubMed

Singh, Romi; Wang, Ouhong

2013-11-01

Clinical studies are being placed in emerging markets as part of global drug development programs to access large pool of eligible patients and to benefit from a cost effective structure. However, over the last few years, the definition of "emerging markets" is being revisited, especially from a regulatory perspective. For purposes of this article, countries outside US, EU and the traditional "western countries" are discussed. Multiple factors are considered for placement of clinical studies such as adherence to Good Clinical Practice (GCP), medical infrastructure & standard of care, number of eligible patients, etc. This article also discusses other quantitative factors such as country's GDP, patent applications, healthcare expenditure, healthcare infrastructure, corruption, innovation, etc. These different factors and indexes are correlated to the number of clinical studies ongoing in the "emerging markets". R&D, healthcare expenditure, technology infrastructure, transparency, and level of innovation, show a significant correlation with the number of clinical trials being conducted in these countries. This is the first analysis of its kind to evaluate and correlate the various other factors to the number of clinical studies in a country. © 2013.

Usefulness of two clinical chorioamnionitis definitions in predicting neonatal infectious outcomes: a systematic review.

PubMed

Avila, Cecilia; Willins, Jennifer L; Jackson, Matthew; Mathai, Jacob; Jabsky, Marina; Kong, Alex; Callaghan, Fiona; Ishkin, Selda; Shroyer, A Laurie W

2015-09-01

To assess the usefulness of two definitions of acute clinical chorioamnionitis (ACCA) in predicting risk of neonatal infectious outcomes (NIO) and mortality, the first definition requiring maternal fever alone (Fever), and the second requiring ≥ 1 Gibbs criterion besides fever (Fever + 1). PubMed, Web of Science, and the Cochrane Database of Systematic Reviews were searched from January 1, 1979 to April 9, 2013. Twelve studies were reviewed (of 316 articles identified): three studies with term patients, four with preterm premature rupture of membranes (PPROM) patients, and five mixed studies with mixed gestational ages and/or membrane status (intact and/or ruptured). Both definitions demonstrated an increased NIO risk for ACCA versus non-ACCA patients, with an odds ratio increase for the Fever + 1 definition that was about twofold larger than the Fever definition. As the Fever definition demonstrated increased NIO risk for ACCA versus non-ACCA patients, the Fever alone ACCA definition should be used to trigger future clinical treatment in many clinical situations. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

PubMed

Kaplan, Frederick S; Andolina, Jeffrey R; Adamson, Peter C; Teachey, David T; Finklestein, Jerry Z; Ebb, David H; Whitehead, Benjamin; Jacobs, Benjamin; Siegel, David M; Keen, Richard; Hsiao, Edward; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

PubMed Central

Graham, Stephen M.; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E.; Gale, Marianne; Gie, Robert P.; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C.; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J.; McNeeley, David F.; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R.; Swaminathan, Soumya; Wingfield, Claire

2012-01-01

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. PMID:22448023

Recommendations for the Definition of Clinical Responder in Insulin Preservation Studies

PubMed Central

Gitelman, Stephen E.; Palmer, Jerry P.

2014-01-01

Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve β-cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month β-cell preservation in type 1 diabetes as measured by 2-h–stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of β-cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. PMID:24722251

Evaluation of the WHO clinical case definition for pediatric HIV infection in Bloemfontein, South Africa.

PubMed

van Gend, Christine L; Haadsma, Maaike L; Sauer, Pieter J J; Schoeman, Cornelius J

2003-06-01

The WHO clinical case definition for pediatric HIV infection has been designed to be used in countries where diagnostic laboratory resources are limited. We evaluated the WHO case definition to determine whether it is a useful instrument to discriminate between HIV-positive and HIV-negative children. In addition, clinical features not included in this case definition were recorded. We recorded clinical data from 300 consecutively admitted children in a state hospital in Bloemfontein, South Africa, and tested these children for HIV infection. A total of 222 children were included in the study; 69 children (31.1 per cent) were HIV positive. The sensitivity of the WHO case definition in this study was 14.5 per cent, the specificity was 98.6 per cent. Apart from weight loss and generalized dermatitis, the signs of the WHO case definition were significantly more often seen in HIV-positive than in HIV-negative children. Of the clinical signs not included in the WHO case definition, marasmus and hepatosplenomegaly especially occurred more frequently in HIV-positive children. Based on these findings we composed a new case definition consisting of four signs: marasmus, hepatosplenomegaly, oropharyngeal candidiasis, and generalized lymphadenopathy. HIV infection is suspected in a child presenting with at least two of these four signs. The sensitivity of this case definition was 63.2 per cent, the specificity was 96.0 per cent. We conclude that in this study the WHO case definition was not a useful instrument to discriminate between HIV-positive and HIV-negative children, mainly because its sensitivity was strikingly low. The simplified case definition we propose, proved to be more sensitive than the WHO case definition (63.2 vs. 14.5 per cent), whilst its specificity remained high.

The impact of Magnetic Resonance Imaging (MRI) on ischemic stroke detection and incidence: minimal impact within a population-based study.

PubMed

Kleindorfer, Dawn; Khoury, Jane; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Adeoye, Opeolu; Ferioli, Simona; Khatri, Pooja; Kissela, Brett M

2015-09-25

There are several situations in which magnetic resonance imaging (MRI) might impact whether an cerebrovascular event is considered a new stroke. These include clinically non-focal events with positive imaging for acute cerebral infarction, and worsening of older symptoms without evidence of new infarction on MRI. We sought to investigate the impact of MRI on stroke detection and stroke incidence, by describing agreement between a strictly clinical definition of stroke and a definition based on physician opinion, including MRI imaging findings. All hospitalized strokes that occurred in five Ohio and Northern Kentucky counties (population 1.3 million) in the calendar year of 2005 were identified using ICD-9 discharge codes 430-436. The two definitions used were: "clinical case definition" which included sudden onset focal neurologic symptoms referable to a vascular territory for >24 h, compared to the "best clinical judgment of the physician definition", which considers all relevant information, including neuroimaging findings. The 95% confidence intervals (CI) for the incidence rates were calculated assuming a Poisson distribution. Rates were standardized to the 2000 U.S. population, adjusting for age, race, and sex, and included all age groups. There were 2403 ischemic stroke events in 2269 patients; 1556 (64%) had MRI performed. Of the events, 2049 (83%) were cases by both definitions, 185 (7.7%) met the clinical case definition but were non-cases in the physician's opinion and 169 (7.0%) were non-cases by clinical definition but were cases in the physician's opinion. There was no significant difference in the incidence rates of first-ever or total ischemic strokes generated by the two different definitions, or when only those with MRI imaging were included. We found that MRI findings do not appear to substantially change stroke incidence estimates, as the strictly clinical definition of stroke did not significantly differ from a definition that included imaging findings. Including MRI in the case definition "rules out" almost the same number of strokes as it "rules in".

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents

PubMed Central

Ferkol, Thomas W.; Davis, Stephanie D.; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D.; Sagel, Scott D.; Milla, Carlos; Olivier, Kenneth N.; Sullivan, Kelli M.; Zariwala, Maimoona A.; Pittman, Jessica E.; Shapiro, Adam J.; Carson, Johnny L.; Krischer, Jeffrey; Hazucha, Milan J.

2016-01-01

Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Methods: Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0–18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as “definite PCD” (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), “probable/possible PCD” (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and “other diagnosis or undefined.” Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. Measurements and Main Results: From 534 participants 18 years of age and younger, 205 were identified as having “definite PCD” (including 164 with two mutations in a PCD-associated gene), 187 were categorized as “other diagnosis or undefined,” and 142 were defined as having “probable/possible PCD.” Participants with “definite PCD” were compared with the “other diagnosis or undefined” group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Conclusions: Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167). PMID:27070726

Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research.

PubMed

Hill, Adam T; Haworth, Charles S; Aliberti, Stefano; Barker, Alan; Blasi, Francesco; Boersma, Wim; Chalmers, James D; De Soyza, Anthony; Dimakou, Katerina; Elborn, J Stuart; Feldman, Charles; Flume, Patrick; Goeminne, Pieter C; Loebinger, Michael R; Menendez, Rosario; Morgan, Lucy; Murris, Marlene; Polverino, Eva; Quittner, Alexandra; Ringshausen, Felix C; Tino, Gregory; Torres, Antoni; Vendrell, Montserrat; Welte, Tobias; Wilson, Rob; Wong, Conroy; O'Donnell, Anne; Aksamit, Timothy

2017-06-01

There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis. Copyright ©ERS 2017.

Defining competency-based evaluation objectives in family medicine

PubMed Central

Lawrence, Kathrine; Allen, Tim; Brailovsky, Carlos; Crichton, Tom; Bethune, Cheri; Donoff, Michel; Laughlin, Tom; Wetmore, Stephen; Carpentier, Marie-Pierre; Visser, Shaun

2011-01-01

Abstract Objective To develop key features for priority topics previously identified by the College of Family Physicians of Canada that, together with skill dimensions and phases of the clinical encounter, broadly describe competence in family medicine. Design Modified nominal group methodology, which was used to develop key features for each priority topic through an iterative process. Setting The College of Family Physicians of Canada. Participants An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian family medicine context with respect to region, sex, language, community type, and experience. Methods The group used a modified Delphi process to derive a detailed operational definition of competence, using multiple iterations until consensus was achieved for the items under discussion. The group met 3 to 4 times a year from 2000 to 2007. Main findings The group analyzed 99 topics and generated 773 key features. There were 2 to 20 (average 7.8) key features per topic; 63% of the key features focused on the diagnostic phase of the clinical encounter. Conclusion This project expands previous descriptions of the process of generating key features for assessment, and removes this process from the context of written examinations. A key-features analysis of topics focuses on higher-order cognitive processes of clinical competence. The project did not define all the skill dimensions of competence to the same degree, but it clearly identified those requiring further definition. This work generates part of a discipline-specific, competency-based definition of family medicine for assessment purposes. It limits the domain for assessment purposes, which is an advantage for the teaching and assessment of learners. A validation study on the content of this work would ensure that it truly reflects competence in family medicine. PMID:21998245

A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria

PubMed Central

Angus, Derek C.; Seymour, Christopher W.; Coopersmith, Craig M.; Deutschman, Clifford; Klompas, Michael; Levy, Mitchell M.; Martin, Greg S.; Osborn, Tiffany M.; Rhee, Chanu; Watson, R. Scott

2016-01-01

Although sepsis was described more than 2,000 years ago, and clinicians still struggle to define it, there is no “gold standard,” and multiple competing approaches and terms exist. Challenges include the ever-changing knowledge base that informs our understanding of sepsis, competing views on which aspects of any potential definition are most important, and the tendency of most potential criteria to be distributed in at-risk populations in such a way as to hinder separation into discrete sets of patients. We propose that the development and evaluation of any definition or diagnostic criteria should follow four steps: 1) define the epistemologic underpinning, 2) agree on all relevant terms used to frame the exercise, 3) state the intended purpose for any proposed set of criteria, and 4) adopt a scientific approach to inform on their usefulness with regard to the intended purpose. Usefulness can be measured across six domains: 1) reliability (stability of criteria during retesting, between raters, over time, and across settings), 2) content validity (similar to face validity), 3) construct validity (whether criteria measure what they purport to measure), 4) criterion validity (how new criteria fare compared to standards), 5) measurement burden (cost, safety, and complexity), and 6) timeliness (whether criteria are available concurrent with care decisions). The relative importance of these domains of usefulness depends on the intended purpose, of which there are four broad categories: 1) clinical care, 2) research, 3) surveillance, and 4) quality improvement and audit. This proposed methodologic framework is intended to aid understanding of the strengths and weaknesses of different approaches, provide a mechanism for explaining differences in epidemiologic estimates generated by different approaches, and guide the development of future definitions and diagnostic criteria. PMID:26901559

A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria.

PubMed

Angus, Derek C; Seymour, Christopher W; Coopersmith, Craig M; Deutschman, Clifford S; Klompas, Michael; Levy, Mitchell M; Martin, Gregory S; Osborn, Tiffany M; Rhee, Chanu; Watson, R Scott

2016-03-01

Although sepsis was described more than 2,000 years ago, and clinicians still struggle to define it, there is no "gold standard," and multiple competing approaches and terms exist. Challenges include the ever-changing knowledge base that informs our understanding of sepsis, competing views on which aspects of any potential definition are most important, and the tendency of most potential criteria to be distributed in at-risk populations in such a way as to hinder separation into discrete sets of patients. We propose that the development and evaluation of any definition or diagnostic criteria should follow four steps: 1) define the epistemologic underpinning, 2) agree on all relevant terms used to frame the exercise, 3) state the intended purpose for any proposed set of criteria, and 4) adopt a scientific approach to inform on their usefulness with regard to the intended purpose. Usefulness can be measured across six domains: 1) reliability (stability of criteria during retesting, between raters, over time, and across settings), 2) content validity (similar to face validity), 3) construct validity (whether criteria measure what they purport to measure), 4) criterion validity (how new criteria fare compared to standards), 5) measurement burden (cost, safety, and complexity), and 6) timeliness (whether criteria are available concurrent with care decisions). The relative importance of these domains of usefulness depends on the intended purpose, of which there are four broad categories: 1) clinical care, 2) research, 3) surveillance, and 4) quality improvement and audit. This proposed methodologic framework is intended to aid understanding of the strengths and weaknesses of different approaches, provide a mechanism for explaining differences in epidemiologic estimates generated by different approaches, and guide the development of future definitions and diagnostic criteria.

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraus, J; Thomas, E; Wu, X

2016-06-15

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC.more » Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.« less

Avoiding Communication in Dense Linear Algebra

DTIC Science & Technology

2013-08-16

Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.1.1 Asymptotic Notation . . . . . . . . . . . . . . . . . . . . . . . . . . . 6...and parallelizing Strassen’s matrix multiplication algorithm (Chapter 11). 6 Chapter 2 Preliminaries 2.1 Notation and Definitions In this section we...between computations and algo- rithms). The following definition is based on [56]: Definition 2.1. A classical algorithm in linear algebra is one that

Behçet's disease.

PubMed

Saadoun, David; Wechsler, Bertrand

2012-04-12

DEFINITION OF THE DISEASE: Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnosis is only based on clinical criteria. DIFFERRENTIAL DIAGNOSIS: It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn's disease, Takayasu's arteritis, polychondritis or antiphospholipid syndrome need to be considered. Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. The prognosis is severe due to the ocular, neurological and arterial involvement.

Definition of drug-resistant epilepsy: is it evidence based?

PubMed

Wiebe, Samuel

2013-05-01

Clinical case definitions are the cornerstone of clinical communication and of clinical and epidemiologic research. The ramifications of establishing a case definition are extensive, including potentially large changes in epidemiologic estimates of frequency, and decisions for clinical management. Yet, defining a condition entails numerous challenges such as defining the scope and purpose, incorporating the strongest evidence base with clinical expertise, accounting for patients' values, and considering impact on care. The clinical case definition of drug-resistant epilepsy, in addition, must address what constitutes an adequate intervention for an individual drug, what are the outcomes of relevance, what period of observation is sufficient to determine success or failure, how many medications should be tried, whether seizure frequency should play a role, and what is the role of side effects and tolerability. On the other hand, the principles of evidence-based medicine (EBM) aim at providing a systematic approach to incorporating the best available evidence into the process of clinical decision for individual patients. The case definition of drug-resistant epilepsy proposed by the the International League Against Epilepsy (ILAE) in 2009 is evaluated in terms of the principles of EBM as well as the stated goals of the authors of the definition. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

[The clinical, serological and morphological analysis of 91 patients with cystic echinococcosis following surgery].

PubMed

Mıman, Ozlem; Atambay, Metin; Aydin, Nasuhi Engin; Daldal, Nilgün

2010-01-01

Cystic echinococcocis (CE) is a zoonotic infection caused by metacestod form of Echinococcus granulosus. In this study, 91 patients with CE were revealed according to their gender, age, symptoms, cyst localization and size, and also to their preoperative serologic analysis results. These patients were recruited in Pathology Department of Inonu University, School of Medicine, Turgut Ozal Medical Center between January 2002 and December 2005. They had already undergone surgery following the preliminary diagnosis of CE and were diagnosed definitively after histopathological analysis. Thirty-seven of them were female (41%) and the rest were male (n=54, 59%). Mean age was 36.24 ± 20.35 (range: 4-80 years). Lung and liver were the most common localizations for CE cysts (n=67, 73.63%). Fifty patients' preoperative serological analysis (IHA) were already available (55%) and 46 of them (92%) were positive. Since histopathological definitive diagnosis was CE, false negative result rate was assessed as 8%. Intraabdominal CE cyst localization was found related with bigger cyst size and multiple organ involvement. Symptom duration was correlated with cyst size (p < 0.05; r < sup > 2 < /sup > =0.09). IHA results were failed to be found related with clinical features of the cysts.

[Fat embolism syndrome after bone fractures].

PubMed

Campo-López, C; Flors-Villaverde, P; Calabuig-Alborch, J R

2012-11-01

To review the incidence, clinical features, diagnosis, therapy and mortality rates of fat embolism syndrome (FES) in a tertiary referral hospital in the last decade. Retrospective and descriptive study of patients diagnosed with post-traumatic FES between january 2001 and december 2011. A total of 19 patients, 16 men and 3 women, with an average age of 27 years were evaluated. All had long bone fractures, multiple in 78.9%, as a result of multiple injuries. Respiratory symptoms were the most frequent (89.5%), followed by neurological symptoms (68.4%) and petechial rash (63.2%). The average time of presentation of the syndrome after admission was 42 hours. All patients underwent early stabilisation of the fracture prior to the embolic event. Steroids prophylaxis was not used in any of the cases. Definitive surgical treatment had mean delay of 7 days. The mean hospital stay was 34 days. The overall incidence of FES was 0.14%, and mortality was 10.5%. Post-traumatic FES mainly affected young patients with multiple injuries and long bone fractures. They all had symptoms of the classic clinical triad (respiratory, neurological, rash) after an initial asymptomatic period of less than 2 days. The overall incidence was low. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Road map for the clinical application of the basophil activation test in food allergy.

PubMed

Santos, A F; Shreffler, W G

2017-09-01

The diagnosis of IgE-mediated food allergy based solely on the clinical history and the documentation of specific IgE to whole allergen extract or single allergens is often ambiguous, requiring oral food challenges (OFCs), with the attendant risk and inconvenience to the patient, to confirm the diagnosis of food allergy. This is a considerable proportion of patients assessed in allergy clinics. The basophil activation test (BAT) has emerged as having superior specificity and comparable sensitivity to diagnose food allergy, when compared with skin prick test and specific IgE. BAT, therefore, may reduce the number of OFC required for accurate diagnosis, particularly positive OFC. BAT can also be used to monitor resolution of food allergy and the clinical response to immunomodulatory treatments. Given the practicalities involved in the performance of BAT, we propose that it can be applied for selected cases where the history, skin prick test and/or specific IgE are not definitive for the diagnosis of food allergy. In the cases that the BAT is positive, food allergy is sufficiently confirmed without OFC; in the cases that BAT is negative or the patient has non-responder basophils, OFC may still be indicated. However, broad clinical application of BAT demands further standardization of the laboratory procedure and of the flow cytometry data analyses, as well as clinical validation of BAT as a diagnostic test for multiple target allergens and confirmation of its feasibility and cost-effectiveness in multiple settings. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Statin intolerance - a question of definition.

PubMed

Algharably, Engi Abdel-Hady; Filler, Iris; Rosenfeld, Stephanie; Grabowski, Katja; Kreutz, Reinhold

2017-01-01

Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed. Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested. Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.

Behçet's disease

PubMed Central

2012-01-01

Definition of the disease Behçet disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular and central nervous system manifestations. Epidemiology BD seems to cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. European cases are often described, not exclusively in the migrant population. Clinical description The clinical spectrum includes oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Etiology The etiopathogenesis of the disease remains unknown, although genetic predisposition, environmental factors and immunological abnormalities have been implicated. Diagnostic methods Diagnosis is only based on clinical criteria. Differrential diagnosis It depends on the clinical presentation of BD, but sarcoidosis, multiple sclerosis, Crohn’s disease, Takayasu’s arteritis, polychondritis or antiphospholipid syndrome need to be considered. Management Treatment is symptomatic using steroids and immunomodulatory therapy. It is efficient depending on the rapidity of initiation, the compliance, and the duration of therapy. Prognosis The prognosis is severe due to the ocular, neurological and arterial involvement. PMID:22497990

Acute viral bronchiolitis: Physician perspectives on definition and clinically important outcomes.

PubMed

Fernandes, Ricardo M; Andrade, Maria Gabriela; Constant, Carolina; Malveiro, Duarte; Magalhães, Manuel; Abreu, Daisy; Azevedo, Inês; Sousa, Eduarda; Salgado, Rizério; Bandeira, Teresa

2016-07-01

Two key limitations hamper intervention research in bronchiolitis: the absence of a clear definition of disease, and the heterogeneous choice of outcome measures in current clinical trials. We assessed how paediatricians and general practitioners (GPs) perceived definition and clinically important outcomes in bronchiolitis. A nationwide online survey (ABBA study) was conducted through the Portuguese Society of Paediatrics and GPs' mailing lists. We assessed agreement with statements on bronchiolitis definition, and participants were asked to score the relative importance of several outcomes. Principal component analysis (PCA) explored dimensions underlying disease definition. Outcomes were ranked by mean score and proportion given highest score. We included 514 paediatricians and 165 GPs (overall 59% were board-certified). Most paediatricians (76.5%) agreed with a definition based on coryza, wheezing and/or crackles/rales, compared to 38.1% GPs (P < 0.001). Less than 5% physicians agreed with a definition commonly used in clinical trials (<12 months, first episode of wheeze). We retained three dimensions on PCA: one based on coryza, rales/crepitations and no sudden onset; another on number of episodes and age; and a third on wheeze. Dimensions varied by physician specialization and training (P < 0.01). Hospital admission and respiratory distress were top rated outcomes by both groups of physicians. Physician definitions of bronchiolitis have considerable variability and often mismatch those of clinical trials. Rating of important outcomes was consistent. Our results highlight the need for a robust standardized definition of acute bronchiolitis in infants and support the development of a core outcome set for future clinical trials. Pediatr Pulmonol. 2016;51:724-732. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Determining the in-hospital cost of bleeding in patients undergoing percutaneous coronary intervention.

PubMed

Ewen, Edward F; Zhao, Liping; Kolm, Paul; Jurkovitz, Claudine; Fidan, Dogan; White, Harvey D; Gallo, Richard; Weintraub, William S

2009-06-01

The economic impact of bleeding in the setting of nonemergent percutaneous coronary intervention (PCI) is poorly understood and complicated by the variety of bleeding definitions currently employed. This retrospective analysis examines and contrasts the in-hospital cost of bleeding associated with this procedure using six bleeding definitions employed in recent clinical trials. All nonemergent PCI cases at Christiana Care Health System not requiring a subsequent coronary artery bypass were identified between January 2003 and March 2006. Bleeding events were identified by chart review, registry, laboratory, and administrative data. A microcosting strategy was applied utilizing hospital charges converted to costs using departmental level direct cost-to-charge ratios. The independent contributions of bleeding, both major and minor, to cost were determined by multiple regression. Bootstrap methods were employed to obtain estimates of regression parameters and their standard errors. A total of 6,008 cases were evaluated. By GUSTO definitions there were 65 (1.1%) severe, 52 (0.9%) moderate, and 321 (5.3%) mild bleeding episodes with estimated bleeding costs of $14,006; $6,980; and $4,037, respectively. When applying TIMI definitions there were 91 (1.5%) major and 178 (3.0%) minor bleeding episodes with estimated costs of $8,794 and $4,310, respectively. In general, the four additional trial-specific definitions identified more bleeding events, provided lower estimates of major bleeding cost, and similar estimates of minor bleeding costs. Bleeding is associated with considerable cost over and above interventional procedures; however, the choice of bleeding definition impacts significantly on both the incidence and economic consequences of these events.

Achieving high-value cardiac imaging: challenges and opportunities.

PubMed

Wiener, David H

2014-01-01

Cardiac imaging is under intense scrutiny as a contributor to health care costs, with multiple initiatives under way to reduce and eliminate inappropriate testing. Appropriate use criteria are valuable guides to selecting imaging studies but until recently have focused on the test rather than the patient. Patient-centered means are needed to define the true value of imaging for patients in specific clinical situations. This article provides a definition of high-value cardiac imaging. A paradigm to judge the efficacy of echocardiography in the absence of randomized controlled trials is presented. Candidate clinical scenarios are proposed in which echocardiography constitutes high-value imaging, as well as stratagems to increase the likelihood that high-value cardiac imaging takes place in those circumstances. Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

[Thrombotic microangiopathy].

PubMed

Beutel, G; Kielstein, J T; Ganser, A

2013-09-01

Thrombotic microangiopathy should be suspected every time the combination of microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as well as renal and/or neurologic abnormalities occurs. The general term thrombotic microangiopathy includes different subtypes of the disease leading to abnormalities in multiple organ systems by endothelial injury and formation of platelet-rich thrombi in small vessels. The main types include thrombotic thrombocytopenic purpura in case of dominant neurologic abnormalities and the hemolytic uremic syndrome in case of acute kidney injury, respectively. Although these syndromes differ in their etiologies, clinical features, response to treatment, and prognosis, an early initiation of a direct therapeutic intervention frequently determines the clinical course of the patient. Irrespectively of the underlying etiology, plasma exchange is an essential component of acute therapeutic intervention while ongoing diagnostics are used to identify the definite treatment.

Enacting relationships in marriage and family therapy: a conceptual and operational definition of an enactment.

PubMed

Davis, Sean D; Butler, Mark H

2004-07-01

Enactments are a potential common clinical process factor contributing to positive outcomes in many relational therapies. Enactments provide therapists a medium for mediating relationships through simultaneous experiential intervention and change at multiple levels of relationships--including specific relationship disagreements and problems, interaction process surrounding these issues, and underlying emotions and attachment issues confounded with those problems. We propose a model of enactments in marriage and family therapy, consisting of three components--initiation operations, intervention operations, and evaluation operations. We offer a conceptual framework to help clinicians know when and to what purpose to use this model of enactments. We provide an operational description of each component of an enactment, exemplifying them using a hypothetical clinical vignette. Directions for future research are suggested.

Differential diagnosis of suspected multiple sclerosis: a consensus approach

PubMed Central

Miller, DH; Weinshenker, BG; Filippi, M; Banwell, BL; Cohen, JA; Freedman, MS; Galetta, SL; Hutchinson, M; Johnson, RT; Kappos, L; Kira, J; Lublin, FD; McFarland, HF; Montalban, X; Panitch, H; Richert, JR; Reingold, SC; Polman, CH

2008-01-01

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. PMID:18805839

Mapping Turnaround Times (TAT) to a Generic Timeline: A Systematic Review of TAT Definitions in Clinical Domains

PubMed Central

2011-01-01

Background Assessing turnaround times can help to analyse workflows in hospital information systems. This paper presents a systematic review of literature concerning different turnaround time definitions. Our objectives were to collect relevant literature with respect to this kind of process times in hospitals and their respective domains. We then analysed the existing definitions and summarised them in an appropriate format. Methods Our search strategy was based on Pubmed queries and manual reviews of the bibliographies of retrieved articles. Studies were included if precise definitions of turnaround times were available. A generic timeline was designed through a consensus process to provide an overview of these definitions. Results More than 1000 articles were analysed and resulted in 122 papers. Of those, 162 turnaround time definitions in different clinical domains were identified. Starting and end points vary between these domains. To illustrate those turnaround time definitions, a generic timeline was constructed using preferred terms derived from the identified definitions. The consensus process resulted in the following 15 terms: admission, order, biopsy/examination, receipt of specimen in laboratory, procedure completion, interpretation, dictation, transcription, verification, report available, delivery, physician views report, treatment, discharge and discharge letter sent. Based on this analysis, several standard terms for turnaround time definitions are proposed. Conclusion Using turnaround times to benchmark clinical workflows is still difficult, because even within the same clinical domain many different definitions exist. Mapping of turnaround time definitions to a generic timeline is feasible. PMID:21609424

Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

PubMed

Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

2011-02-01

Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

Amylolytic activity of IgM and IgG antibodies from patients with multiple sclerosis.

PubMed

Saveliev, Andrew N; Ivanen, Dina R; Kulminskaya, Anna A; Ershova, Nadezhda A; Kanyshkova, Tat'yana G; Buneva, Valentina N; Mogelnitskii, Alexander S; Doronin, Boris M; Favorova, Olga O; Nevinsky, Georgy A; Neustroev, Kirill N

2003-05-01

IgG and IgM antibodies from the sera of patients with multiple sclerosis (MS) were found to possess amylolytic activity hydrolyzing alpha-(1-->4)-glucosyl linkages of maltooligosaccharides, glycogen, and several artificial substrates. Individual IgM fractions isolated from 54 analyzed patients with the clinically definite diagnoses of MS had approximately three orders of magnitude higher specific amylolytic activity than that for healthy donors, whereas IgG from only a few patients had high amylolytic activity. Strict criteria were used to prove that the amylolytic activity of IgMs and IgGs is their intrinsic property and is not due to any enzyme contamination. Fab fragments produced from IgM and IgG fractions of the MS patients displayed the same amylolytic activity. IgMs from various patients demonstrated different modes of action in hydrolyzing maltooligosaccharides.

The relative contributions of processing speed and cognitive load to working memory accuracy in multiple sclerosis.

PubMed

Leavitt, Victoria M; Lengenfelder, Jean; Moore, Nancy B; Chiaravalloti, Nancy D; DeLuca, John

2011-06-01

Cognitive symptoms of multiple sclerosis (MS) include processing-speed deficits and working memory impairment. The precise manner in which these deficits interact in individuals with MS remains to be explicated. We hypothesized that providing more time on a complex working memory task would result in performance benefits for individuals with MS relative to healthy controls. Fifty-three individuals with clinically definite MS and 36 matched healthy controls performed a computerized task that systematically manipulated cognitive load. The interval between stimuli presentations was manipulated to provide increasing processing time. The results confirmed that individuals with MS who have processing-speed deficits significantly improve in performance accuracy when given additional time to process the information in working memory. Implications of these findings for developing appropriate cognitive rehabilitation interventions are discussed.

The motivation, skills, and decision-making model of "drug abuse" prevention.

PubMed

Sussman, Steve; Earleywine, Mitchell; Wills, Thomas; Cody, Christine; Biglan, Tony; Dent, Clyde W; Newcomb, Michael D

2004-01-01

This article summarizes the theoretical basis for targeted prevention programs as they apply to different high-risk groups. We explain the advantages and disadvantages of different definitions of risk and discuss strategies for preventing drug use related problems in high-risk youth. Productive prevention programs for many at-risk groups share similar components, including those that address motivation, skills, and decision making. We present key aspects of these three components and link them to theories in clinical psychology, social psychology, sociology, and chemical dependence treatment. Among a total of 29 promising targeted prevention programs, we describe examples of empirically evaluated, intensive interventions that have made a positive impact on the attitudes and behavior of multiple problem youth. Incorporating the perspectives of multiple disciplines appears essential for progress in drug abuse and other problem behavior prevention.

service line analytics in the new era.

PubMed

Spence, Jay; Seargeant, Dan

2015-08-01

To succeed under the value-based business model, hospitals and health systems require effective service line analytics that combine inpatient and outpatient data and that incorporate quality metrics for evaluating clinical operations. When developing a framework for collection, analysis, and dissemination of service line data, healthcare organizations should focus on five key aspects of effective service line analytics: Updated service line definitions. Ability to analyze and trend service line net patient revenues by payment source. Access to accurate service line cost information across multiple dimensions with drill-through capabilities. Ability to redesign key reports based on changing requirements. Clear assignment of accountability.

Research on infertility: which definition should we use?

PubMed

Larsen, Ulla

2005-04-01

Different definitions of infertility are used in clinical practice as well as in epidemiological and demographic research. This study assessed whether the definition makes a difference for estimates of the prevalence and sociodemographic differentials of infertility and whether one definition would be applicable in both research and clinical practice. Cross-sectional study. Moshi town in northern Tanzania. Community-based sample of 1,125 women, ages 20 to 44 years, in first union. Six definitions of infertility. Similar levels and sociodemographic characteristics of infertile women were obtained from asking the question "How long have you tried to get pregnant?" and from secondary data collected in a birth history that included date of marriage, date of last birth, current contraceptive use, and whether the woman wants another child. The infertility definition made a difference. The World Health Organization definition based on 24 months of trying to get pregnant is recommended as the definition that is useful in clinical practice and research among different disciplines.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

PubMed

Caloyeras, John P; Zhang, Bin; Wang, Cheng; Eriksson, Marianne; Fredrikson, Sten; Beckmann, Karola; Knappertz, Volker; Pohl, Christoph; Hartung, Hans-Peter; Shah, Dhvani; Miller, Jeffrey D; Sandbrink, Rupert; Lanius, Vivian; Gondek, Kathleen; Russell, Mason W

2012-05-01

To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Application of Array Comparative Genomic Hybridization in Newborns with Multiple Congenital Anomalies.

PubMed

Szczałuba, Krzysztof; Nowakowska, Beata; Sobecka, Katarzyna; Smyk, Marta; Castaneda, Jennifer; Klapecki, Jakub; Kutkowska-Kaźmierczak, Anna; Śmigiel, Robert; Bocian, Ewa; Radkowski, Marek; Demkow, Urszula

2016-01-01

Major congenital anomalies are detectable in 2-3 % of the newborn population. Some of their genetic causes are attributable to copy number variations identified by array comparative genomic hybridization (aCGH). The value of aCGH screening as a first-tier test in children with multiple congenital anomalies has been studied and consensus adopted. However, array resolution has not been agreed upon, specifically in the newborn or infant population. Moreover, most array studies have been focused on mixed populations of intellectual disability/developmental delay with or without multiple congenital anomalies, making it difficult to assess the value of microarrays in newborns. The aim of the study was to determine the optimal quality and clinical sensitivity of high-resolution array comparative genomic hybridization in neonates with multiple congenital anomalies. We investigated a group of 54 newborns with multiple congenital anomalies defined as two or more birth defects from more than one organ system. Cytogenetic studies were performed using OGT CytoSure 8 × 60 K microarray. We found ten rearrangements in ten newborns. Of these, one recurrent syndromic microduplication was observed, whereas all other changes were unique. Six rearrangements were definitely pathogenic, including one submicroscopic and five that could be seen on routine karyotype analysis. Four other copy number variants were likely pathogenic. The candidate genes that may explain the phenotype were discussed. In conclusion, high-resolution array comparative hybridization can be applied successfully in newborns with multiple congenital anomalies as the method detects a significant number of pathogenic changes, resulting in early diagnoses. We hypothesize that small changes previously considered benign or even inherited rearrangements should be classified as potentially pathogenic at least until a subsequent clinical assessment would exclude a developmental delay or dysmorphism.

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study.

PubMed

Solomon, Andrew J; Bourdette, Dennis N; Cross, Anne H; Applebee, Angela; Skidd, Philip M; Howard, Diantha B; Spain, Rebecca I; Cameron, Michelle H; Kim, Edward; Mass, Michele K; Yadav, Vijayshree; Whitham, Ruth H; Longbrake, Erin E; Naismith, Robert T; Wu, Gregory F; Parks, Becky J; Wingerchuk, Dean M; Rabin, Brian L; Toledano, Michel; Tobin, W Oliver; Kantarci, Orhun H; Carter, Jonathan L; Keegan, B Mark; Weinshenker, Brian G

2016-09-27

To characterize patients misdiagnosed with multiple sclerosis (MS). Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis. © 2016 American Academy of Neurology.

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

PubMed

Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

2015-01-01

Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p<0.05). Significant correlations between BHvis/total-FLAIR lesion volume and clinical disability were obtained for a wide range of T1-RT thresholds. The highest correlation for BHvis and total-FLAIR lesion masks were found at T1-RT>1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). Clinical-radiological correlations in MS patients are increased by application of T1-RT thresholds. With the short acquisition time of the MP2RAGE sequences, quantitative T1 maps could be easily established in clinical studies.

Using a Delphi Technique to Seek Consensus Regarding Definitions, Descriptions and Classification of Terms Related to Implicit and Explicit Forms of Motor Learning

PubMed Central

Kleynen, Melanie; Braun, Susy M.; Bleijlevens, Michel H.; Lexis, Monique A.; Rasquin, Sascha M.; Halfens, Jos; Wilson, Mark R.; Beurskens, Anna J.; Masters, Rich S. W.

2014-01-01

Background Motor learning is central to domains such as sports and rehabilitation; however, often terminologies are insufficiently uniform to allow effective sharing of experience or translation of knowledge. A study using a Delphi technique was conducted to ascertain level of agreement between experts from different motor learning domains (i.e., therapists, coaches, researchers) with respect to definitions and descriptions of a fundamental conceptual distinction within motor learning, namely implicit and explicit motor learning. Methods A Delphi technique was embedded in multiple rounds of a survey designed to collect and aggregate informed opinions of 49 international respondents with expertise related to motor learning. The survey was administered via an online survey program and accompanied by feedback after each round. Consensus was considered to be reached if ≥70% of the experts agreed on a topic. Results Consensus was reached with respect to definitions of implicit and explicit motor learning, and seven common primary intervention strategies were identified in the context of implicit and explicit motor learning. Consensus was not reached with respect to whether the strategies promote implicit or explicit forms of learning. Discussion The definitions and descriptions agreed upon may aid translation and transfer of knowledge between domains in the field of motor learning. Empirical and clinical research is required to confirm the accuracy of the definitions and to explore the feasibility of the strategies that were identified in research, everyday practice and education. PMID:24968228

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2014-01-01

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

What Restructuring Is: In Search of a Definition.

ERIC Educational Resources Information Center

Harvey, Glen; Crandall, David P.

Educational restructuring, an emerging concept without a single definition or a definitive model, supports the notion of multiple alternatives. Typical school improvement and excellence initiatives do not, by themselves, constitute restructuring. Restructuring means that schools should be organized according to children's learning needs. To…

Impact of definition and procedures used for absent blood culture data on the rate of intravascular catheter infection during parenteral nutrition.

PubMed

Austin, P D; Hand, K S; Elia, M

2016-06-01

Diagnosis of intravascular catheter infection may be affected by the definition and procedures applied in the absence of blood culture data. To examine the extent to which different definitions of catheter infection and procedures for handling absent blood culture data can affect reported catheter infection rates. Catheter infection rates were established in a cohort of hospitalized patients administered parenteral nutrition according to three clinical and four published definitions. Paired and unpaired comparisons were made using available case analyses, sensitivity analyses and intention-to-categorize analyses. Complete data were available for each clinical definition (N = 193), and there were missing data (4.1-26.9%) for the published definitions. In an available case analysis, the catheter infection rate was 13.0-36.8% for the clinical definitions and 2.1-12.4% for the published definitions. For the published definitions, the rate was 1.6-32.1% in a sensitivity analysis and 11.4-16.9% in an intention-to-categorize analysis, with suggestion of bias towards a higher catheter infection rate in those with missing data, in keeping with the analyses of the clinical definitions. For paired comparisons, the strength of agreement between definitions varied from 'poor' (Cohen's kappa <0.21) to 'very good' (Cohen's kappa ≥0.81). The use of different definitions of catheter infection and procedures applied in the absence of blood culture data produced widely different catheter infection rates, which could compromise measurements or comparisons of service quality or study outcome. As such, there is a need to establish and use a valid, consistent and practical definition. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria.

PubMed

Solaro, Claudio; Cella, M; Signori, Alessio; Martinelli, Vittorio; Radaelli, Marta; Centonze, D; Sica, F; Grasso, M G; Clemenzi, A; Bonavita, S; Esposito, S; Patti, F; D'Amico, E; Cruccu, G; Truini, A

2018-04-01

Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

PubMed Central

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

Classification Systems for Individual Differences in Multiple-task Performance and Subjective Estimates of Workload

NASA Technical Reports Server (NTRS)

Damos, D. L.

1984-01-01

Human factors practitioners often are concerned with mental workload in multiple-task situations. Investigations of these situations have demonstrated repeatedly that individuals differ in their subjective estimates of workload. These differences may be attributed in part to individual differences in definitions of workload. However, after allowing for differences in the definition of workload, there are still unexplained individual differences in workload ratings. The relation between individual differences in multiple-task performance, subjective estimates of workload, information processing abilities, and the Type A personality trait were examined.

International consensus on preliminary definitions of improvement in adult and juvenile myositis.

PubMed

Rider, Lisa G; Giannini, Edward H; Brunner, Hermine I; Ruperto, Nicola; James-Newton, Laura; Reed, Ann M; Lachenbruch, Peter A; Miller, Frederick W

2004-07-01

To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials. Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were >/=75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation. The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by >/=20%, with no more than 2 worse by >/=25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials. Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials.

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

[Acute schizophrenia concept and definition: investigation of a French psychiatrist population].

PubMed

Baylé, F J; Misdrahi, D; Llorca, P M; Lançon, C; Olivier, V; Quintin, P; Azorin, J M

2005-01-01

For schizophrenic disorders, the clinical conception of "acute state" is widely used in clinical settings to assess the effectiveness of therapeutic programs as well as epidemiological studies. Schizophrenic-specific symptomatology modification, need for hospitalization, significant change in care, disturbances in social behavior or suicide attempts were all used to define acute schizophrenic state. The decision to hospitalize is frequently used to define acute state but refers to multiple factors such as mood disorder, suicide attempts, drug abuse or social and environmental problems. Indeed, several and distinct definitions in a criteria basis form are available but no one has reached consensus. Because recognition of acute schizophrenic state remains based on the subjective clinician's advice, epidemiological and therapeutic studies fail in validity and reliability. The aim of the study was to evaluate how a population of French psychiatrists define criteria and therapeutic targets of acute schizophrenic state in their clinical practice. Psychiatrists filled out a self administered interview. At the time the interview was given, clinicians were notified that they were participating in a clinical consensus survey about schizophrenia. Six major indicators for acute state definition based on the literature data were proposed: general schizophrenic symptomatology modification (depression, anxiety, agitation, impulsivity/aggressiveness), specific schizophrenic symptomatology modification (positive symptoms, negative symptoms, disorganization), need for hospitalization, significant change in care, disturbance in social behavior and lastly, suicidal behavior. Minimal duration (1.2 or 4 weeks) of general and specific schizophrenic symptomatology modification required to define acute state were evaluated. The booklet included the 30 PANSS symptoms listed with their definitions. Among this symptom list, clinicians were instructed to select the ten criteria which they estimated best defined the acute state, followed by the ten most important target symptoms to be treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among the six majors indicators proposed to define acute state 75% of psychiatrists considered 1 to 3 criteria. Three were more frequently rated, including core schizophrenic symptomatology disturbance (68.4%), general schizophrenic symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other criteria were rated as follows: need for hospitalization (26.8%), significant change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of psychiatrists the definition of acute state requires the presence of specific schizophrenic symptomatology for a minimal duration of one week. Two weeks with general symptomatology was required for 45.5% of psychiatrists to define acute state. Symptoms more often rated within the four first choices for acute state definition included delusions, conceptual disorganization, hallucinatory behavior and excitement. Except for grandiosity, all the PANSS positive subscale items were chosen to be included in the definition (delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution and hostility). Four items, including anxiety, depression, uncontrolled hostility, inner tension from the general psychopathology subscale were chosen as part of the ten most important criteria to define acute state. On the PANSS negative subscale (blunted affect, emotional withdrawal, poor relationships, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation and stereotyped thinking), no item was rated to be included in the acute state definition. The highest rated symptoms among the four first choices for treatment included delusions, hallucinatory behavior, excitement and anxiety. The ten most important criteria for treatment were the same as for acute state definition with differences in frequency. Excited state, depression and suspiciousness/persecution were more rated for treatment than definition whereas delusion, hostility and conceptual disorganization were less rated as treatment target than definition criteria. In clinical practice, recognition of acute schizophrenic state is underscored by the association of specific schizophrenic symptomatology (positive symptoms, negative symptoms, disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety, depression, agitation) of schizophrenia. For most clinicians, acute state definition requires specific symptom for a minimum of one week and other non-specific indicators such as suicidal behaviour have to be taken into account. With regard to PANSS criteria, most positive schizophrenic symptoms and some general schizophrenic symptoms are necessary for definition and designated as treatment priorities. Negative symptoms were not taken into account. Hallucinatory behavior is the first symptom rated in definition and is considered by psychiatrists as the absolute therapeutic priority. This survey could be a first step in the construction of an operational and consensual definition. This definition is strongly needed as a valid measurement in therapeutic and epidemiological outcome studies, which remain at least partly based on clinician subjective judgment.

47 CFR 73.402 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Digital Audio Broadcasting § 73.402 Definitions. (a) DAB. Digital audio broadcast stations are those radio... into multiple channels for additional audio programming uses. (g) Datacasting. Subdividing the digital...

47 CFR 73.402 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Digital Audio Broadcasting § 73.402 Definitions. (a) DAB. Digital audio broadcast stations are those radio... into multiple channels for additional audio programming uses. (g) Datacasting. Subdividing the digital...

47 CFR 73.402 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Digital Audio Broadcasting § 73.402 Definitions. (a) DAB. Digital audio broadcast stations are those radio... into multiple channels for additional audio programming uses. (g) Datacasting. Subdividing the digital...

47 CFR 73.402 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Digital Audio Broadcasting § 73.402 Definitions. (a) DAB. Digital audio broadcast stations are those radio... into multiple channels for additional audio programming uses. (g) Datacasting. Subdividing the digital...

Multiple sclerosis with predominant, severe cognitive impairment

PubMed Central

Staff, Nathan P.; Lucchinetti, Claudia F.; Keegan, B. Mark

2009-01-01

Objective To describe the characteristics of multiple sclerosis (MS) presenting with severe cognitive impairment as its primary disabling manifestation. Design Retrospective case series. Setting Tertiary referral center. Patients Patients were identified through the Mayo Clinic data retrieval system (1996–2008) with definite MS (McDonald criteria) and severe cognitive impairment as their primary neurological symptom without accompanying significant MS-related impairment or alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting inclusion criteria were compared regarding demographics, clinical course and radiological features. Main Outcome Measures Demographic, clinical, and radiological characteristics of the disease. Results Twelve patients were men. The median age of the first clinical symptom suggestive of CNS demyelination was 33 years, and severe MS-related cognitive impairment developed at a median of 39 years. Cognitive impairment could be dichotomized as subacute fulminant (n=9) or chronic progressive (n=14) in presentation, which corresponded to subsequent relapsing or progressive MS courses. Study patients commonly exhibited psychiatric (65%), mild cerebellar (57%) and cortical symptoms and signs (e.g. seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%), where documented, smoked cigarettes. Brain MRI demonstrated diffuse cerebral atrophy in 16 and gadolinium enhancing lesions in 11. Asymptomatic spinal cord MRI lesions were present in 12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in improving these patients. Conclusions We describe patients with MS whose clinical phenotype is characterized by severe cognitive dysfunction and prominent cortical and psychiatric signs presenting as a subacute fulminant or chronic progressive clinical course. Cigarette smokers may be over represented in this phenotype. PMID:19752304

Recommendations for the definition of clinical responder in insulin preservation studies.

PubMed

Beam, Craig A; Gitelman, Stephen E; Palmer, Jerry P

2014-09-01

Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve β-cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month β-cell preservation in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of β-cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Utility of providing a concussion definition in the assessment of concussion history in former NFL players.

PubMed

Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos; Martin, Brett; Chaisson, Christine; Baugh, Christine M; Torres, Alcy; Nowinski, Christopher J; Cantu, Robert C; Stern, Robert A

2017-01-01

Former National Football League (NFL) players' working knowledge of concussion has not yet been evaluated, despite this population being a major clinical research target due to the association between repetitive head impacts (RHI) and long-term clinical impairments. This study examined former NFL players' understanding of the current concussion definition, and the association between number of concussions with clinical function. 95 former NFL players (mean age = 55.29; mean NFL year = 8.10) self-reported number of concussions before being provided with a concussion definition and after being read a modern definition of concussion. Subjects reported number of concussions with loss of consciousness (LOC). Principal Component Analysis of a battery of tests generated behaviour/mood, psychomotor speed/executive function, and verbal and visual memory factor scores. Post-definition number of concussions (median = 50) was five times the pre-definition (median = 10; p < 0.001). Greater pre- (p = 0.019) and post-definition concussions (p = 0.036) correlated with worse behaviour/mood scores, after controlling for years of football played, with specific effects for depressive symptoms and impulsivity. LOC did not account for variance beyond number of concussions. Practitioners and clinical researchers should provide a definition of concussion in the assessment of concussion history in former football players to facilitate accuracy and standardization.

The International Glossary on Infertility and Fertility Care, 2017.

PubMed

Zegers-Hochschild, Fernando; Adamson, G David; Dyer, Silke; Racowsky, Catherine; de Mouzon, Jacques; Sokol, Rebecca; Rienzi, Laura; Sunde, Arne; Schmidt, Lone; Cooke, Ian D; Simpson, Joe Leigh; van der Poel, Sheryl

2017-09-01

Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. None. N/A. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The International Glossary on Infertility and Fertility Care, 2017.

PubMed

Zegers-Hochschild, Fernando; Adamson, G David; Dyer, Silke; Racowsky, Catherine; de Mouzon, Jacques; Sokol, Rebecca; Rienzi, Laura; Sunde, Arne; Schmidt, Lone; Cooke, Ian D; Simpson, Joe Leigh; van der Poel, Sheryl

2017-09-01

Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. None. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium†

PubMed Central

Leon, Martin B.; Piazza, Nicolo; Nikolsky, Eugenia; Blackstone, Eugene H.; Cutlip, Donald E.; Kappetein, Arie Pieter; Krucoff, Mitchell W.; Mack, Michael; Mehran, Roxana; Miller, Craig; Morel, Marie-angèle; Petersen, John; Popma, Jeffrey J.; Takkenberg, Johanna J.M.; Vahanian, Alec; van Es, Gerrit-Anne; Vranckx, Pascal; Webb, John G.; Windecker, Stephan; Serruys, Patrick W.

2011-01-01

Objectives To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Background Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials. Methods and results The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended. Conclusion Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes. PMID:21216739

[How to Understand "Clinical Ethics" and "Research Ethics" in Clinical Settings--Incorporation of IRB, REC, and CEC in Hospital Organizations].

PubMed

Ita, Koichiro

2016-02-01

As the traditional definition of "medical ethics" has recently changed markedly with advances in medical knowledge and technology, medical doctors and researchers in Japan are required to understand and apply both research and clinical ethics. Quite frequently, ethical problems in clinical settings cannot be addressed by the simple application of good will, hard work, and perseverance by medical personnel. The Ministry of Health, Labour and Welfare (MHLW) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) have jointly published "Ethical Guidelines for Clinical Studies;" however, clear guidelines (legal, ministerial, or governmental) outlining the expectations regarding clinical ethics do not exist. All medical personnel face deep ethical dilemmas. In these instances, if the fulfillment of 'ethics' relies solely on the capacity of personnel to apply their own individual moral efforts, the result will be burn-out among these workers who have a strong sense of responsibility. In order to avoid this, a system which comprises multiple physicians, nurses, and other personnel must be established, allowing collaboration when an appropriate response is required. A major factor supporting this approach is the offering of Clinical Ethics Consultations.

Definition of healthcare-associated influenza: A review and results from an international survey.

PubMed

Munier-Marion, Elodie; Bénet, Thomas; Vanhems, Philippe

2017-09-01

To describe definitions of healthcare-associated influenza (HAI) in recent literature and in hospitals participating in a survey of Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) members. A review with PubMed search was undertaken to retrieve articles published between 2008 and 2016, focusing on the subject headings "influenza, human" and "cross infection." Definitions of clinical influenza-like illness (ILI) and HAI were identified. An invitation to participate in the survey was sent to 218 SRN members via email. Of 75 articles on HAI included in the review, 30 presented a standardized definition of clinical ILI based on fever (100%), cough (80%), and sore throat (70%). Forty studies (53%) contained a standardized HAI definition, grounded on threshold delay from admission in 29 of them, this delay ranging from 48 to 196 hour (median: 72 hour). Fifty-five SRN members responded to the survey, with a standardized definition of HAI adopted by 76% of them. This definition was based on clinical features for 24%, virological features for 31%, and both for 45%. Fever (mean threshold: 38.0°C) was part of the definition for 82%. The features required most frequently in the clinical definition were cough (46%) and sore throat (26%). Median threshold delay between admission and symptoms onset adopted for HAI definition was 48 hour (range: 24-96 hour). This work underlined the heterogeneity of HAI definitions in different countries. A standardized definition would be helpful to evaluate HAI spread, outcomes in patients and healthcare systems, and the impact of prevention measures, including vaccination. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

A data management system for engineering and scientific computing

NASA Technical Reports Server (NTRS)

Elliot, L.; Kunii, H. S.; Browne, J. C.

1978-01-01

Data elements and relationship definition capabilities for this data management system are explicitly tailored to the needs of engineering and scientific computing. System design was based upon studies of data management problems currently being handled through explicit programming. The system-defined data element types include real scalar numbers, vectors, arrays and special classes of arrays such as sparse arrays and triangular arrays. The data model is hierarchical (tree structured). Multiple views of data are provided at two levels. Subschemas provide multiple structural views of the total data base and multiple mappings for individual record types are supported through the use of a REDEFINES capability. The data definition language and the data manipulation language are designed as extensions to FORTRAN. Examples of the coding of real problems taken from existing practice in the data definition language and the data manipulation language are given.

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

Epidemiologic research using probabilistic outcome definitions.

PubMed

Cai, Bing; Hennessy, Sean; Lo Re, Vincent; Small, Dylan S

2015-01-01

Epidemiologic studies using electronic healthcare data often define the presence or absence of binary clinical outcomes by using algorithms with imperfect specificity, sensitivity, and positive predictive value. This results in misclassification and bias in study results. We describe and evaluate a new method called probabilistic outcome definition (POD) that uses logistic regression to estimate the probability of a clinical outcome using multiple potential algorithms and then uses multiple imputation to make valid inferences about the risk ratio or other epidemiologic parameters of interest. We conducted a simulation to evaluate the performance of the POD method with two variables that can predict the true outcome and compared the POD method with the conventional method. The simulation results showed that when the true risk ratio is equal to 1.0 (null), the conventional method based on a binary outcome provides unbiased estimates. However, when the risk ratio is not equal to 1.0, the traditional method, either using one predictive variable or both predictive variables to define the outcome, is biased when the positive predictive value is <100%, and the bias is very severe when the sensitivity or positive predictive value is poor (less than 0.75 in our simulation). In contrast, the POD method provides unbiased estimates of the risk ratio both when this measure of effect is equal to 1.0 and not equal to 1.0. Even when the sensitivity and positive predictive value are low, the POD method continues to provide unbiased estimates of the risk ratio. The POD method provides an improved way to define outcomes in database research. This method has a major advantage over the conventional method in that it provided unbiased estimates of risk ratios and it is easy to use. Copyright © 2014 John Wiley & Sons, Ltd.

Café-au-lait Macules and Neurofibromatosis Type 1: A Review of the Literature.

PubMed

Bernier, Anne; Larbrisseau, Albert; Perreault, Sebastien

2016-07-01

The first sign of neurofibromatosis type 1 (NF1) in a child is often the presence of multiple café-au-lait macules. Although previous studies reported that almost individuals with multiple café-au-lait macules will eventually develop NF1 based on clinical criteria, recent studies and clinical observations suggest that a significant percentage of them do not have NF1. We conducted the first systematic review of the literature on the prevalence of definitive NF1 among patients referred for isolated café-au-lait macules, searching more precisely for the proportion of those patients who do not have NF1. Because we now know that the presence of café-au-lait macules and freckling might not distinguish between NF1 and other conditions such as Legius syndrome, definitive NF1 was defined as the presence of café-au-lait macules with or without freckling plus one of the following: Lisch nodules, neurofibroma, plexiform neurofibroma, bone dysplasia, optic pathway glioma, or familial history of NF1. Six articles reported sufficient data to meet our inclusion criteria. Grouping all studies together, we found that 19.5% to 57.1% of all patients with isolated café-au-lait macules did not have a diagnosis of NF1 after follow-up or genetic testing. A significant portion of the patients presenting with isolated café-au-lait macules at initial consultation might not have NF1. Genetic testing could help guide the follow-up of those patients, but further evidence is required to make recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

Definitions of School Bullying in Taiwan: A Comparison of Multiple Perspectives

ERIC Educational Resources Information Center

Cheng, Ying-Yao; Chen, Li-Ming; Ho, Hsiao-Chi; Cheng, Chih-Ling

2011-01-01

Investigating teachers' and students' different definitions of school bullying is important for necessary prevention and effective intervention. This study compared definitions of bullying from the perspectives of bystanders, bullies, victims, and educators. A total of 1,558 secondary educators and students in Taiwan participated in this research,…

75 FR 16957 - Energy Conservation Program: Test Procedures for Battery Chargers and External Power Supplies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... Procedures C. Review of Single-Voltage External Power Supply Test Procedure D. Multiple-Voltage External...) Deletions of Existing Definitions (b) Revisions to Existing Definitions (c) Additions of New Definitions 4. Test Apparatus and General Instructions (a) Confidence Intervals (b) Temperature (c) AC Input Voltage...

Situational Context Affects Definiteness Preferences: Accommodation of Presuppositions

ERIC Educational Resources Information Center

Clifton, Charles, Jr.

2013-01-01

In 4 experiments, we used self-paced reading and eye tracking to demonstrate that readers are, under some conditions, sensitive to the presuppositions of definite versus indefinite determiner phrases (DPs). Reading was faster when the context stereotypically provided a single possible referent for a definite DP or multiple possible referents for…

Terminology, the importance of defining.

PubMed

van Mil, J W Foppe; Henman, Martin

2016-06-01

Multiple terms and definitions exist to describe specific aspects of pharmacy practice and service provision. This commentary explores the reasons for different interpretations of words and concepts in pharmaceutical care and pharmacy practice research. Reasons for this variation can be found in language, culture, profession and may also depend on developments over time. A list of words is provided where the authors think that currently multiple interpretations are possible. To make sure that the reader understands the essence, it seems imperative that authors include a definition of the topics that they actually study in their papers, and that they clearly cite existing definitions or refer to collections of definitions such as existing glossaries. It is important that presenters, authors and reviewers of pharmacy practice papers pay more attention to this aspect of describing studies.

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion.

PubMed

Zatta, A J; McQuilten, Z K; Mitra, B; Roxby, D J; Sinha, R; Whitehead, S; Dunkley, S; Kelleher, S; Hurn, C; Cameron, P A; Isbister, J P; Wood, E M; Phillips, L E

2014-07-01

The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies. Data were extracted on all patients who received red blood cell (RBC) transfusions in 2010 at three tertiary Australian hospitals. MT patients were identified according to three definitions: ≥10 units RBC in 24 h (10/24 h), ≥6 units RBC in 6 h (6/6 h) and ≥5 units RBC in 4 h (5/4 h). Clinical coding data were used to assign bleeding context. Data on in-hospital mortality were also extracted. Five hundred and forty-two patients met at least one MT definition, with 236 (44%) included by all definitions. The most inclusive definition was 5/4 h (508 patients, 94%) followed by 6/6 h (455 patients, 84%) and 10/24 h (251 patients, 46%). Importantly, 40-55% of most types of critical bleeding events and 82% of all obstetric haemorrhage cases were excluded by the 10/24 h definition. Patients who met both the 5/4 h and 10/24 h definitions were transfused more RBCs (19 vs. 8 median total RBC units; P < 0·001), had longer ventilation time (120 vs. 55 h; P < 0·001), median ICU (149 vs. 99 h; P < 0·001) and hospital length of stay (23 vs. 18 h; P = 0·006) and had a higher in-hospital mortality rate (23·3% vs. 16·4%; P = 0·050). The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort. © 2014 International Society of Blood Transfusion.

The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited.

PubMed

Cremers, Ruben G; Aben, Katja K; van Oort, Inge M; Sedelaar, J P Michiel; Vasen, Hans F; Vermeulen, Sita H; Kiemeney, Lambertus A

2016-07-01

The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form of prostate cancer (SPC). HPC patients were identified through a national registry of HPC families in the Netherlands, selecting patients diagnosed from the year 2000 onward (n = 324). SPC patients were identified from the Netherlands Cancer Registry (NCR) between 2003 and 2006 for a population-based study into the genetic susceptibility of PC (n = 1,664). Detailed clinical data were collected by NCR-registrars, using a standardized registration form. Follow-up extended up to the end of 2013. Differences between the groups were evaluated by cross-tabulations and tested for statistical significance while accounting for familial dependency of observations by GEE. Differences in progression-free and overall survival were evaluated using χ(2) testing with GEE in a proportional-hazards model. HPC patients were on average 3 years younger at diagnosis, had lower PSA values, lower Gleason scores, and more often locally confined disease. Of the HPC patients, 35% had high-risk disease (NICE-criteria) versus 51% of the SPC patients. HPC patients were less often treated with active surveillance. Kaplan-Meier 5-year progression-free survival after radical prostatectomy was comparable for HPC (78%) and SPC (74%; P = 0.30). The 5-year overall survival was 85% (95%CI 81-89%) for HPC versus 80% (95%CI 78-82%) for SPC (P = 0.03). HPC has a favorable clinical phenotype but patients more often underwent radical treatment. The major limitation of HPC is the absence of a genetics-based definition of HPC, which may lead to over-diagnosis of PC in men with a family history of prostate cancer. The HPC definition should, therefore, be re-evaluated, aiming at a reduction of over-diagnosis and overtreatment among men with multiple relatives diagnosed with PC. Prostate 76:897-904, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

Clinical and epidemiological features of human rabies cases in the Philippines: a review from 1987 to 2006.

PubMed

Dimaano, Efren M; Scholand, Stephen J; Alera, Maria Theresa P; Belandres, Domingo B

2011-07-01

Rabies viral infection causes a fatal encephalomyelitis. In humans, classic features include hydrophobia, aerophobia, hypersalivation, agitation, and neurological symptoms. In the Philippines, canine rabies contributes to a significant burden of human disease. We retrospectively reviewed the medical records of 1839 patients admitted to San Lazaro Hospital, Manila, Philippines between 1987 and 2006, with a clinical diagnosis of rabies. We used the World Health Organization case definition for clinical rabies, which is defined by the presence of hydrophobia. Male patients outnumbered females by 2.2 to 1 and twice the number of adults were affected compared with children. Most patients were indigent. Dog bites occurred more than cat bites (97.1% vs. 2.9%) and most cases were caused by a single bite (86.2%), compared to multiple bites (8.7%). Bites to the face, head, and neck led to shorter incubation times, yet the incubation period varied, with most cases (42.7%) occurring in the bracket of 91-365 days post-exposure. Clinical symptoms included hydrophobia in all cases, as per our case definition, and aerophobia in 95.5%; only 9.4% had fever, 9.2% exhibited restlessness, and 6.7% exhibited hypersalivation. Localized neurological symptoms included pain (4.1%), numbness (2.6%), and itching (2.3%). None of the patients received appropriate post-exposure prophylaxis (PEP). This study examines the largest cohort of rabies patients reported to-date. Better understanding of clinical disease manifestations may help in salvage efforts to save patients with rabies. Knowledge of epidemiological factors will improve preventative efforts to reduce suffering from rabies. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2013-10-22

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5), which are of uncertain prognostic importance. In addition, for both the MI types, cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than using an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG), which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013. Published by Elsevier Inc.

Does retrieval practice enhance learning and transfer relative to restudy for term-definition facts?

PubMed

Pan, Steven C; Rickard, Timothy C

2017-09-01

In many pedagogical contexts, term-definition facts that link a concept term (e.g., "vision") with its corresponding definition (e.g., "the ability to see") are learned. Does retrieval practice involving retrieval of the term (given the definition) or the definition (given the term) enhance subsequent recall, relative to restudy of the entire fact? Moreover, does any benefit of retrieval practice for the term transfer to later recall of the definition, or vice versa? We addressed those questions in 4 experiments. In each, subjects first studied term-definition facts and then trained on two thirds of the facts using multiple-choice tests with feedback. Half of the test questions involved recalling terms; the other half involved recalling definitions. The remaining facts were either not trained (Experiment 1) or restudied (Experiments 2-4). A 48-hr delayed multiple-choice (Experiments 1-2) or short answer (Experiments 3a-4) final test assessed recall of all terms or all definitions. Replicating and extending prior research, retrieval practice yielded improved recall and positive transfer relative to no training. Relative to restudy, however, retrieval practice consistently enhanced subsequent term retrieval, enhanced subsequent definition retrieval only after repeated practice, and consistently yielded at best minimal positive transfer in either direction. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Defining Chronic Cough: A Systematic Review of the Epidemiological Literature

PubMed Central

Song, Woo-Jung; Chang, Yoon-Seok; Faruqi, Shoaib; Kang, Min-Koo; Kim, Ju-Young; Kang, Min-Gyu; Kim, Sujeong; Jo, Eun-Jung; Lee, Seung-Eun; Kim, Min-Hye; Plevkova, Jana; Park, Heung-Woo

2016-01-01

Purpose Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics. Methods A systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions. Results A total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I2=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity. Conclusions This study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required. PMID:26739408

Using Claims Data to Generate Clinical Flags Predicting Short-term Risk of Continued Psychiatric Hospitalizations

PubMed Central

Stein, Bradley D.; Pangilinan, Maria; Sorbero, Mark J; Marcus, Sue; Donahue, Sheila; Xu, Yan; Smith, Thomas E; Essock, Susan M

2014-01-01

Objective As health information technology advances, efforts to use administrative data to inform real-time treatment planning for individuals are increasing, despite few empirical studies demonstrating that such administrative data predict subsequent clinical events. Medicaid claims for individuals with frequent psychiatric hospitalizations were examined to test how well patterns of service use predict subsequent high short-term risk of continued psychiatric hospitalizations. Methods Medicaid claims files from New York and Pennsylvania were used to identify Medicaid recipients aged 18-64 with two or more inpatient psychiatric admissions during a target year ending March 31, 2009. Definitions from a quality-improvement initiative were used to identify patterns of inpatient and outpatient service use and prescription fills suggestive of clinical concerns. Generalized estimating equations and Markov models were applied to examine claims through March, 2011, to see what patterns of service use were sufficiently predictive of additional hospitalizations to be clinically useful. Results 11,801 unique individuals in New York and 1,859 in Pennsylvania identified met the cohort definition. In both Pennsylvania and New York, multiple recent hospitalizations, but not failure to use outpatient services or failure to fill medication prescriptions, were significant predictors of high risk of continued frequent hospitalizations, with odds ratios greater than 4.0. Conclusions Administrative data can be used to identify individuals at high risk of continued frequent hospitalizations. Such information could be used by payers and system administrators to authorize special services (e.g., mobile outreach) for such individuals as part of efforts to promote service engagement and prevent rapid rehospitalizations. PMID:25022360

Cochrane Lecture 1997. What evidence do we need for evidence based medicine?

PubMed Central

Hart, J T

1997-01-01

As presently understood, evidence based medicine aims to advance practice from its traditional unverifiable mix of art and science to rational use of measurable inputs and outputs. In practice, however, its advocates accept uncritically a desocialised definition of science, assume that major clinical decisions are taken at the level of secondary specialist rather than primary generalist care, and ignore the multiple nature of most clinical problems, as well as the complexity of social problems within which clinical problems arise and have to be solved. These reductionist assumptions derive from the use of evidence based medicine as a tool for managed care in a transactional model for consultations. If these assumptions persist, they will strengthen reification of disease and promote the episodic output of process regardless of health outcome. We need to work within a different paradigm based on development of patients as co-producers rather than consumers, promoting continuing output of health gain through shared decisions using all relevant evidence, within a broader, socialised definition of science. Adoption of this model would require a major social and cultural shift for health professionals. This shift has already begun, promoted by changes in public attitudes to professional authority, changes in the relation of professionals to managers, and pressures for improved effectiveness and efficiency which, contrary to received wisdom, seem more likely to endorse cooperative than transactional clinical production. Progress on these lines is resisted by rapidly growing and extremely powerful economic and political interests. Health professionals and strategists have yet to recognise and admit the existence of this choice. PMID:9519124

Coding update of the SMFM definition of low risk for cesarean delivery from ICD-9-CM to ICD-10-CM.

PubMed

Armstrong, Joanne; McDermott, Patricia; Saade, George R; Srinivas, Sindhu K

2017-07-01

In 2015, the Society for Maternal-Fetal Medicine developed a low risk for cesarean delivery definition based on administrative claims-based diagnosis codes described by the International Classification of Diseases, Ninth Revision, Clinical Modification. The Society for Maternal-Fetal Medicine definition is a clinical enrichment of 2 available measures from the Joint Commission and the Agency for Healthcare Research and Quality measures. The Society for Maternal-Fetal Medicine measure excludes diagnosis codes that represent clinically relevant risk factors that are absolute or relative contraindications to vaginal birth while retaining diagnosis codes such as labor disorders that are discretionary risk factors for cesarean delivery. The introduction of the International Statistical Classification of Diseases, 10th Revision, Clinical Modification in October 2015 expanded the number of available diagnosis codes and enabled a greater depth and breadth of clinical description. These coding improvements further enhance the clinical validity of the Society for Maternal-Fetal Medicine definition and its potential utility in tracking progress toward the goal of safely lowering the US cesarean delivery rate. This report updates the Society for Maternal-Fetal Medicine definition of low risk for cesarean delivery using International Statistical Classification of Diseases, 10th Revision, Clinical Modification coding. Copyright © 2017. Published by Elsevier Inc.

Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial.

PubMed

Warke, Kim; Al-Smadi, Jamal; Baxter, David; Walsh, Deirdre M; Lowe-Strong, Andrea S

2006-01-01

This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population. Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate. Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods. Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population.

From normal response to clinical problem: definition and clinical features of fear of cancer recurrence.

PubMed

Lebel, Sophie; Ozakinci, Gozde; Humphris, Gerald; Mutsaers, Brittany; Thewes, Belinda; Prins, Judith; Dinkel, Andreas; Butow, Phyllis

2016-08-01

Research to date on fear of cancer recurrence (FCR) shows that moderate to high FCR affects 22-87 % of cancer survivors and is associated with higher psychological morbidity (Simard et al J Cancer Surviv 7:300-322, 2013). Despite growing research interest in FCR, the lack of consensus on its definition and characteristics when it reaches a clinical level has impeded knowledge transfer into patient services. In order to address these gaps, expert researchers, policy makers, trainees, and patient advocates attended a 2-day colloquium at the University of Ottawa in August 2015. A Delphi method was used to identify the most relevant definition of FCR, and the attendees generated possible diagnostic characteristics of clinical FCR. After three rounds of discussion and voting, the attendees reached consensus on a new definition of FCR: "Fear, worry, or concern relating to the possibility that cancer will come back or progress." Regarding clinical FCR, five possible characteristics were proposed: (1) high levels of preoccupation, worry, rumination, or intrusive thoughts; (2) maladaptive coping; (3) functional impairments; (4) excessive distress; and (5) difficulties making plans for the future. The new proposed definition of FCR reflects the broad spectrum in which patients experience FCR. A consensual definition of FCR and the identification of the essential characteristics of clinical FCR are necessary to accurately and consistently measure FCR severity and to develop effective interventions to treat FCR. We hope this broad definition can encourage further research and the development of inclusive policies for all cancer patients and survivors who are struggling with this issue.

Autoimmune Hepatitis

MedlinePlus

... Living with a Liver Transplant Clinical Trials Nonalcoholic Fatty Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Nonalcoholic Fatty Liver Disease & NASH in Children Definition & Facts Symptoms & Causes ...

Investigations of the pushability behavior of cardiovascular angiographic catheters.

PubMed

Bloss, Peter; Rothe, Wolfgang; Wünsche, Peter; Werner, Christian; Rothe, Alexander; Kneissl, Georg Dieter; Burger, Wolfram; Rehberg, Elisabeth

2003-01-01

The placement of angiographic catheters into the vascular system is a routine procedure in modern clinical business. The definition of objective but not yet available evaluation protocols based on measurable physical quantities correlated to the empirical clinical findings is of utmost importance for catheter manufacturers for in-house product screening and optimization. In this context, we present an assessment of multiple mechanical and surface catheter properties such as static and kinetic friction, bending stiffness, microscopic surface topology, surface roughness, surface free energy and their interrelation. Theoretical framework, description of experimental methods and extensive data measured on several different catheters are provided and in conclusion a testing procedure is defined. Although this procedure is based on the measurement of several physical quantities it can be easily implemented by commercial laboratories testing catheters as it is based on relatively low-cost standard methods.

Glanders: an overview of infection in humans.

PubMed

Van Zandt, Kristopher E; Greer, Marek T; Gelhaus, H Carl

2013-09-03

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.

Glanders: an overview of infection in humans

PubMed Central

2013-01-01

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection. PMID:24004906

Urinary tract infection as a single presenting sign of multiple vaginal foreign bodies: case report and review of the literature.

PubMed

Neulander, Endre Z; Tiktinsky, Alex; Romanowsky, Igor; Kaneti, Jacob

2010-02-01

Vaginal foreign bodies in children usually present with foul-smelling discharge and/or vaginal bleeding. Rarely, these basic clinical diagnostic signs are not present. We report on a 5(1/2)-year-old girl with recurrent lower urinary tract infection as the sole presentation of multiple vaginal foreign bodies. Ultrasound of the lower urinary tract was inconclusive, and cystography indicated for recurrent urinary tract infections was declined by the patient in an outpatient setting. Cystography under general anesthesia raised the suspicion of foreign vaginal objects, and the definitive diagnosis was made by vaginoscopy. The relevant literature covering this subject is reviewed. High level of suspicion and strict basic diagnostic protocol are the most important steps for a timely diagnosis of this condition. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

PubMed

Brenton, J Nicholas; Banwell, Brenda L

2016-01-01

Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis: An Expert Statement.

PubMed

Ruiz, Carlos E; Hahn, Rebecca T; Berrebi, Alain; Borer, Jeffrey S; Cutlip, Donald E; Fontana, Greg; Gerosa, Gino; Ibrahim, Reda; Jelnin, Vladimir; Jilaihawi, Hasan; Jolicoeur, E Marc; Kliger, Chad; Kronzon, Itzhak; Leipsic, Jonathon; Maisano, Francesco; Millan, Xavier; Nataf, Patrick; O'Gara, Patrick T; Pibarot, Philippe; Ramee, Stephen R; Rihal, Charanjit S; Rodes-Cabau, Josep; Sorajja, Paul; Suri, Rakesh; Swain, Julie A; Turi, Zoltan G; Tuzcu, E Murat; Weissman, Neil J; Zamorano, Jose L; Serruys, Patrick W; Leon, Martin B

2017-04-25

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted. Copyright © 2017 American College of Cardiology Foundation and European Society of Cardiology. Published by Elsevier Inc. All rights reserved.

Accuracy of clinical diagnosis versus the World Health Organization case definition in the Amoy Garden SARS cohort.

PubMed

Wong, W N; Sek, Antonio C H; Lau, Rick F L; Li, K M; Leung, Joe K S; Tse, M L; Ng, Andy H W; Stenstrom, Robert

2003-11-01

To compare the diagnostic accuracy of emergency department (ED) physicians with the World Health Organization (WHO) case definition in a large community-based SARS (severe acute respiratory syndrome) cohort. This was a cohort study of all patients from Hong Kong's Amoy Garden complex who presented to an ED SARS screening clinic during a 2-month outbreak. Clinical findings and WHO case definition criteria were recorded, along with ED diagnoses. Final diagnoses were established independently based on relevant diagnostic tests performed after the ED visit. Emergency physician diagnostic accuracy was compared with that of the WHO SARS case definition. Sensitivity, specificity, predictive values and likelihood ratios were calculated using standard formulae. During the study period, 818 patients presented with SARS-like symptoms, including 205 confirmed SARS, 35 undetermined SARS and 578 non-SARS. Sensitivity, specificity and accuracy were 91%, 96% and 94% for ED clinical diagnosis, versus 42%, 86% and 75% for the WHO case definition. Positive likelihood ratios (LR+) were 21.1 for physician judgement and 3.1 for the WHO criteria. Negative likelihood ratios (LR-) were 0.10 for physician judgement and 0.67 for the WHO criteria, indicating that clinician judgement was a much more powerful predictor than the WHO criteria. Physician clinical judgement was more accurate than the WHO case definition. Reliance on the WHO case definition as a SARS screening tool may lead to an unacceptable rate of misdiagnosis. The SARS case definition must be revised if it is to be used as a screening tool in emergency departments and primary care settings.

Patient-physician discussions about costs: definitions and impact on cost conversation incidence estimates.

PubMed

Hunter, Wynn G; Hesson, Ashley; Davis, J Kelly; Kirby, Christine; Williamson, Lillie D; Barnett, Jamison A; Ubel, Peter A

2016-03-31

Nearly one in three Americans are financially burdened by their medical expenses. To mitigate financial distress, experts recommend routine physician-patient cost conversations. However, the content and incidence of these conversations are unclear, and rigorous definitions are lacking. We sought to develop a novel set of cost conversation definitions, and determine the impact of definitional variation on cost conversation incidence in three clinical settings. Retrospective, mixed-methods analysis of transcribed dialogue from 1,755 outpatient encounters for routine clinical management of breast cancer, rheumatoid arthritis, and depression, occurring between 2010-2014. We developed cost conversation definitions using summative content analysis. Transcripts were evaluated independently by at least two members of our multi-disciplinary team to determine cost conversation incidence using each definition. Incidence estimates were compared using Pearson's Chi-Square Tests. Three cost conversation definitions emerged from our analysis: (a) Out-of-Pocket (OoP) Cost--discussion of the patient's OoP costs for a healthcare service; (b) Cost/Coverage--discussion of the patient's OoP costs or insurance coverage; (c) Cost of Illness- discussion of financial costs or insurance coverage related to health or healthcare. These definitions were hierarchical; OoP Cost was a subset of Cost/Coverage, which was a subset of Cost of Illness. In each clinical setting, we observed significant variation in the incidence of cost conversations when using different definitions; breast oncology: 16, 22, 24% of clinic visits contained cost conversation (OOP Cost, Cost/Coverage, Cost of Illness, respectively; P < 0.001); depression: 30, 38, 43%, (P < 0.001); and rheumatoid arthritis, 26, 33, 35%, (P < 0.001). The estimated incidence of physician-patient cost conversation varied significantly depending on the definition used. Our findings and proposed definitions may assist in retrospective interpretation and prospective design of investigations on this topic.

Towards a proposal for a universal diagnostic definition of protein-losing enteropathy in Fontan patients: a systematic review.

PubMed

Udink Ten Cate, Floris Ea; Hannes, Tobias; Germund, Ingo; Khalil, Markus; Huntgeburth, Michael; Apitz, Christian; Brockmeier, Konrad; Sreeram, Narayanswami

2016-07-15

A standardised diagnostic definition of protein-losing enteropathy (PLE) in Fontan patients serves both patient care and research. The present study determined whether a diagnostic definition of PLE was routinely used in published clinical Fontan studies, and to identify potentially relevant diagnostic criteria for composing a uniform PLE definition. A systematic review was conducted in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Published clinical Fontan studies that were written in English and included at least four patients with PLE were selected. PLE definitions were quantitatively analysed using a lateral thinking tool in which definitions were fractionated into constituent pieces of information (building blocks or diagnostic criteria). We identified 364 papers. In the final analysis, data from 62 published articles were extracted. A diagnostic definition of PLE was used in only 27/62 (43.5%) of selected studies, and definitions were very heterogeneous. We identified eight major diagnostic criteria. Hypoalbuminaemia (n=23 studies, 85.2%), clinical presentation (n=18, 66.7%), documentation of enteric protein loss (n=16, 59.3%) and exclusion of other causes of hypoproteinaemia (n=17, 63.0%), were the most frequently used diagnostic criteria. Most studies used three diagnostic variables (n=13/27, 48.1%). Cut-off values for laboratory parameters (serum albumin, protein or faecal α-1-antitrypsin) were frequently incorporated in the PLE definition (n=16, 59.3%). Establishment of a universally accepted PLE definition for routine use in clinical research and daily practice is required. The diagnostic criteria may help constitute a diagnostic PLE definition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Current Assessment and Classification of Suicidal Phenomena using the FDA 2012 Draft Guidance Document on Suicide Assessment: A Critical Review.

PubMed

Sheehan, David V; Giddens, Jennifer M; Sheehan, Kathy Harnett

2014-09-01

Standard international classification criteria require that classification categories be comprehensive to avoid type II error. Categories should be mutually exclusive and definitions should be clear and unambiguous (to avoid type I and type II errors). In addition, the classification system should be robust enough to last over time and provide comparability between data collections. This article was designed to evaluate the extent to which the classification system contained in the United States Food and Drug Administration 2012 Draft Guidance for the prospective assessment and classification of suicidal ideation and behavior in clinical trials meets these criteria. A critical review is used to assess the extent to which the proposed categories contained in the Food and Drug Administration 2012 Draft Guidance are comprehensive, unambiguous, and robust. Assumptions that underlie the classification system are also explored. The Food and Drug Administration classification system contained in the 2012 Draft Guidance does not capture the full range of suicidal ideation and behavior (type II error). Definitions, moreover, are frequently ambiguous (susceptible to multiple interpretations), and the potential for misclassification (type I and type II errors) is compounded by frequent mismatches in category titles and definitions. These issues have the potential to compromise data comparability within clinical trial sites, across sites, and over time. These problems need to be remedied because of the potential for flawed data output and consequent threats to public health, to research on the safety of medications, and to the search for effective medication treatments for suicidality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Karen; Small, William; Portelance, Lorraine

Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aidmore » in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.« less

Recent early clinical drug development for acute kidney injury.

PubMed

Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

2017-02-01

Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis

PubMed Central

Benedict, Ralph HB; DeLuca, John; Phillips, Glenn; LaRocca, Nicholas; Hudson, Lynn D; Rudick, Richard

2017-01-01

Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This topical review provides an overview of research on one particular cognitive measure, the Symbol Digit Modalities Test (SDMT), recognized as being particularly sensitive to slowed processing of information that is commonly seen in MS. The research in MS clearly supports the reliability and validity of this test and recently has supported a responder definition of SDMT change approximating 4 points or 10% in magnitude. PMID:28206827

Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis.

PubMed

Benedict, Ralph Hb; DeLuca, John; Phillips, Glenn; LaRocca, Nicholas; Hudson, Lynn D; Rudick, Richard

2017-04-01

Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This topical review provides an overview of research on one particular cognitive measure, the Symbol Digit Modalities Test (SDMT), recognized as being particularly sensitive to slowed processing of information that is commonly seen in MS. The research in MS clearly supports the reliability and validity of this test and recently has supported a responder definition of SDMT change approximating 4 points or 10% in magnitude.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shipman, Galen M.

These are the slides for a presentation on programming models in HPC, at the Los Alamos National Laboratory's Parallel Computing Summer School. The following topics are covered: Flynn's Taxonomy of computer architectures; single instruction single data; single instruction multiple data; multiple instruction multiple data; address space organization; definition of Trinity (Intel Xeon-Phi is a MIMD architecture); single program multiple data; multiple program multiple data; ExMatEx workflow overview; definition of a programming model, programming languages, runtime systems; programming model and environments; MPI (Message Passing Interface); OpenMP; Kokkos (Performance Portable Thread-Parallel Programming Model); Kokkos abstractions, patterns, policies, and spaces; RAJA, a systematicmore » approach to node-level portability and tuning; overview of the Legion Programming Model; mapping tasks and data to hardware resources; interoperability: supporting task-level models; Legion S3D execution and performance details; workflow, integration of external resources into the programming model.« less

Association between the MMPI-2 restructured form (MMPI-2-RF) and malingered neurocognitive dysfunction among non-head injury disability claimants.

PubMed

Tarescavage, Anthony M; Wygant, Dustin B; Gervais, Roger O; Ben-Porath, Yossef S

2013-01-01

The current study examined the over-reporting Validity Scales of the MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011) in relation to the Slick, Sherman, and Iverson (1999) criteria for the diagnosis of Malingered Neurocognitive Dysfunction in a sample of 916 consecutive non-head injury disability claimants. The classification of Malingered Neurocognitive Dysfunction was based on scores from several cognitive symptom validity tests and response bias indicators built into traditional neuropsychological tests. Higher scores on MMPI-2-RF Validity Scales, particularly the Response Bias Scale (Gervais, Ben-Porath, Wygant, & Green, 2007), were associated with probable and definite Malingered Neurocognitive Dysfunction. The MMPI-2-RF's Validity Scales classification accuracy of Malingered Neurocognitive Dysfunction improved when multiple scales were interpreted. Additionally, higher scores on MMPI-2-RF substantive scales measuring distress, internalizing dysfunction, thought dysfunction, and social avoidance were associated with probable and definite Malingered Neurocognitive Dysfunction. Implications for clinical practice and future directions are noted.

CAD/CAM-generated high-density polymer restorations for the pretreatment of complex cases: a case report.

PubMed

Edelhoff, Daniel; Beuer, Florian; Schweiger, Josef; Brix, Oliver; Stimmelmayr, Michael; Guth, Jan-Frederik

2012-06-01

Complex rehabilitations represent a particular challenge for the restorative team, especially if the vertical dimension of occlusion (VDO) needs to be reconstructed or redefined. The use of provisional acrylic or composite materials allows clinicians to evaluate the treatment objective over a certain period of time and therefore generates a high predictability of the definitive rehabilitation in terms of esthetics and function. CAD/CAM technology enables the use of prefabricated polymer materials, which are fabricated under industrial conditions to form a highly homogeneous structure compared with those of direct fabrication. This increases long-term stability, biocompatibility, and resistance to wear. Furthermore, they offer more suitable CAD/CAM processing characteristics and can be used in thinner thicknesses than ceramic restorative materials. Also, based on the improved long-term stability, the transfer into the definitive restoration can be divided into multiple treatment steps. This article presents different clinical cases with minimally invasive indications for CAD/CAM-fabricated temporary restorations for the pretreatment of complex cases.

Alternative outcome definitions and their effect on the performance of methods for observational outcome studies.

PubMed

Reich, Christian G; Ryan, Patrick B; Schuemie, Martijn J

2013-10-01

A systematic risk identification system has the potential to test marketed drugs for important Health Outcomes of Interest or HOI. For each HOI, multiple definitions are used in the literature, and some of them are validated for certain databases. However, little is known about the effect of different definitions on the ability of methods to estimate their association with medical products. Alternative definitions of HOI were studied for their effect on the performance of analytical methods in observational outcome studies. A set of alternative definitions for three HOI were defined based on literature review and clinical diagnosis guidelines: acute kidney injury, acute liver injury and acute myocardial infarction. The definitions varied by the choice of diagnostic codes and the inclusion of procedure codes and lab values. They were then used to empirically study an array of analytical methods with various analytical choices in four observational healthcare databases. The methods were executed against predefined drug-HOI pairs to generate an effect estimate and standard error for each pair. These test cases included positive controls (active ingredients with evidence to suspect a positive association with the outcome) and negative controls (active ingredients with no evidence to expect an effect on the outcome). Three different performance metrics where used: (i) Area Under the Receiver Operator Characteristics (ROC) curve (AUC) as a measure of a method's ability to distinguish between positive and negative test cases, (ii) Measure of bias by estimation of distribution of observed effect estimates for the negative test pairs where the true effect can be assumed to be one (no relative risk), and (iii) Minimal Detectable Relative Risk (MDRR) as a measure of whether there is sufficient power to generate effect estimates. In the three outcomes studied, different definitions of outcomes show comparable ability to differentiate true from false control cases (AUC) and a similar bias estimation. However, broader definitions generating larger outcome cohorts allowed more drugs to be studied with sufficient statistical power. Broader definitions are preferred since they allow studying drugs with lower prevalence than the more precise or narrow definitions while showing comparable performance characteristics in differentiation of signal vs. no signal as well as effect size estimation.

Clinical consequences of the revised DSM-5 definition of agoraphobia in treatment-seeking anxious youth

PubMed Central

Cornacchio, Danielle; Chou, Tommy; Sacks, Hayley; Pincus, Donna; Comer, Jonathan

2015-01-01

Background In DSM-5, the agoraphobia core symptom criterion has been revised to require fear about multiple situations from across at least two distinct domains in which escape might be difficult or panic-like symptoms might develop. The present study examined patterns and correlates of the recent change in a sample of anxious youth with symptom presentations consistent with the DSM-IV agoraphobia definition and/or specific phobia (SP) to consider how the recent diagnostic change impacts the prevalence and composition of agoraphobia in children and adolescents. Method Analyses (N=151) evaluated impairment and correlates of agoraphobic youth who no longer meet the DSM-5 agoraphobia criteria relative to agoraphobic youth who do meet the new DSM-5 criteria. Secondary analyses compared agoraphobic youth not meeting DSM-5 criteria to SP youth. Results One-quarter of youth with symptom presentations consistent with the DSM-IV agoraphobia definition no longer met criteria for DSM-5 agoraphobia, but showed comparable severity and impairment across most domains to youth who do meet criteria for DSM-5 agoraphobia. Further, these youth showed higher levels of anxiety sensitivity and internalizing psychopathology relative to youth with SP. Conclusions A substantial proportion of impaired youth with considerable agoraphobic symptom presentations have been left without a specified anxiety diagnosis by the DSM-5, which may affect their ability to receive and/or get coverage for services and their representation in treatment evaluations. Future DSM iterations may do well to include a “circumscribed” agoraphobia specifier that would characterize presentations of fear or anxiety about multiple situations, but that do not span across at least two distinct situational domains. PMID:25845579

CLINICAL CONSEQUENCES OF THE REVISED DSM-5 DEFINITION OF AGORAPHOBIA IN TREATMENT-SEEKING ANXIOUS YOUTH.

PubMed

Cornacchio, Danielle; Chou, Tommy; Sacks, Hayley; Pincus, Donna; Comer, Jonathan

2015-07-01

In DSM-5, the agoraphobia core symptom criterion has been revised to require fear about multiple situations from across at least two distinct domains in which escape might be difficult or panic-like symptoms might develop. The present study examined patterns and correlates of the recent change in a sample of anxious youth with symptom presentations consistent with the DSM-IV agoraphobia definition and/or specific phobia (SP) to consider how the recent diagnostic change impacts the prevalence and composition of agoraphobia in children and adolescents. Analyses (N = 151) evaluated impairment and correlates of agoraphobic youth who no longer meet the DSM-5 agoraphobia criteria relative to agoraphobic youth who do meet the new DSM-5 criteria. Secondary analyses compared agoraphobic youth not meeting DSM-5 criteria to SP youth. One-quarter of youth with symptom presentations consistent with the DSM-IV agoraphobia definition no longer met criteria for DSM-5 agoraphobia, but showed comparable severity and impairment across most domains to youth who do meet criteria for DSM-5 agoraphobia. Further, these youth showed higher levels of anxiety sensitivity and internalizing psychopathology relative to youth with SP. A substantial proportion of impaired youth with considerable agoraphobic symptom presentations have been left without a specified anxiety diagnosis by the DSM-5, which may affect their ability to receive and/or get coverage for services and their representation in treatment evaluations. Future DSM iterations may do well to include a "circumscribed" agoraphobia specifier that would characterize presentations of fear or anxiety about multiple situations, but that do not span across at least two distinct situational domains. © 2015 Wiley Periodicals, Inc.

The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

PubMed

Coopersmith, Craig M; Deutschman, Clifford S

2017-03-01

New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

Radiation Therapy for Locally Advanced Esophageal Cancer.

PubMed

Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

2017-04-01

The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

Applicability of McDonald 2010 and Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) 2016 Magnetic Resonance Imaging Criteria for the Diagnosis of Multiple Sclerosis in Sri Lanka.

PubMed

Gamage, Sujani Madhurika Kodagoda; Wijeweera, Indunil; Wijesinghe, Priyangi; Adikari, Sanjaya Bandara; Fink, Katharina; Sominanda, Herath Mudiyanselage Ajith

2018-05-31

The magnetic resonance imaging in multiple sclerosis (MAGNIMS) group recently proposed guidelines to replace the existing dissemination-in-space criteria in McDonald 2010 magnetic resonance imaging (MRI) criteria for diagnosing multiple sclerosis. There has been insufficient research regarding their applicability in Asians. Objective of this study was to determine the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of McDonald 2010 and MAGNIMS 2016 MRI criteria with the aim of verifying their applicability in Sri Lankan patients. Patients with clinically isolated syndrome diagnosed by consultant neurologists were recruited from five major neurology centers. Baseline and follow-up MRI scans were performed within 3 months from the initial presentation and at one year after baseline MRI, respectively. McDonald 2010 and MAGNIMS 2016 MRI criteria were applied to all MRI scans. Patients were followed-up for 2 years to assess the conversion to clinically definite multiple sclerosis (CDMS). The sensitivity, specificity, accuracy, PPV, and NPV for predicting the conversion to CDMS were calculated. Forty-two of 66 patients converted to CDMS. Thirty-seven fulfilled the McDonald 2010 MRI criteria, and 33 converted to CDMS. MAGNIMS 2016 MRI criteria were fulfilled by 29, with 28 converting to CDMS. The sensitivity, specificity, accuracy, PPV, and NPV were 78%, 83%, 64%, 89%, and 69%, respectively, for the McDonald 2010 criteria, and 67%, 96%, 77%, 96%, and 62% for the MAGNIMS 2016 MRI criteria. MAGNIMS 2016 MRI criteria were superior to McDonald 2010 MRI criteria in specificity, accuracy, and PPV, but inferior in sensitivity and NPV. Copyright © 2018 Korean Neurological Association.

Endoscopic Findings and Clinical Outcomes in Ventricular Assist Device Recipients with Gastrointestinal Bleeding

PubMed Central

Elmunzer, B. Joseph; Padhya, Kunjali T.; Lewis, Jason J.; Rangnekar, Amol S.; Saini, Sameer D.; Eswaran, Shanti L.; Scheiman, James M.; Pagani, Francis D.; Haft, Jonathan W.; Waljee, Akbar K.

2015-01-01

Background Gastrointestinal bleeding (GIB) is an important clinical problem in recipients of ventricular assist devices (VAD), although data pertaining to the endoscopic evaluation and management of this complication are limited in the medical literature. Aims We sought to identify the most common endoscopic findings in VAD recipients with GIB, and to better define the diagnostic and therapeutic utility of endosopy for this patient population. Methods Twenty-six subjects with VAD and overt GIB were retrospectively identified. Clinical and endoscopic data were abstracted for each subject on to standardized forms in duplicate and independent fashion. Raw data and descriptive statistics were reported. Results Non-peptic vascular lesions were the most common cause of GIB. A definitive cause of bleeding was identified by endoscopy in almost 60% of subjects. Endoscopic hemostasis was achieved in 14/15 patients in whom bleeding did not stop spontaneously. Rebleeding occurred in 50% of subjects and was successfully retreated or stopped spontaneously in all cases. Colonoscopy did not establish a definitive diagnosis or deliver hemostatic therapy in any case. Conclusions Vascular malformations account for the overwhelming majority of bleeding lesions in VAD patients with GIB. Endoscopy seems to be a safe and effective tool for diagnosing, risk stratifying, and treating this patient population, although multiple endoscopies may be necessary before therapeutic success, and the incidence of rebleeding is high. A prospective multi-center registry is necessary to establish evidence-based management algorithms for VAD recipients with GIB. PMID:21792619

[What is dementia? 2. A fuzzy construct].

PubMed

Derouesné, Christian

2003-03-01

Since the publication of the third edition of the classification of mental disorders by the American Psychiatric Association, APA (DSM-III) in 1980, a large international consensus has been reached to define dementia as a multiple cognitive deficit centered by memory disturbances, interfering with the daily life activities and related to organic brain lesions. The DSM-III defined a diagnostic strategy in two steps. First to make the diagnosis of dementia according to the clinical criteria and then to specify its etiology. The more recent editions of the APA classification did not significantly modify these recommendations. The use of the DSM criteria has allowed important advances in epidemiological, clinical and therapeutic research. However, several criticisms should be addressed to the clinical diagnostic criteria as well as to the current concept of dementia. First, from a theoretical point of view, dementia is not a disease, not even a disorder. It only corresponds to a conventional collection of symptoms. Actually, clinical symptoms of dementia basically depend of the localization of brain lesions. Therefore, there could not be one single dementia syndrome. Similarly, the basis of the search for one "antidementia drug" should be questioned. From a clinical point of view, the DSM-IV criteria present some inaccuracies regarding the description of deficits in memory and executive functions as well as in the assessment of the interference of the cognitive decline with the activities of daily living. The definition of dementia as a purely cognitive deficit results in neglecting its psychological and relational manifestations which play a large part in the detection of dementia and its acceptance by the family. A major criticism concerns the definition of dementia as a sincle clinical entity with memory deficits as the core symptom. This definition is well adapted to Alzheimer's disease but results in delayed diagnosis or misclassification of dementias such as frontotemporal dementia or dementia with Lewy bodies in which memory deficits are minor or late. Presently, diagnostic strategy should be directed towards specific entities such as Alzheimer's disease which can be diagnosed accurately in mildly impaired individuals. It is proposed that the term dementia should only be used to specify a degree of severity of the disease, corresponding to the restriction of the patient's autonomy.

Towards shared patient records: an architecture for using routine data for nationwide research.

PubMed

Knaup, Petra; Garde, Sebastian; Merzweiler, Angela; Graf, Norbert; Schilling, Freimut; Weber, Ralf; Haux, Reinhold

2006-01-01

Ubiquitous information is currently one of the most challenging slogans in medical informatics research. An adequate architecture for shared electronic patient records is needed which can use data for multiple purposes and which is extensible for new research questions. We introduce eardap as architecture for using routine data for nationwide clinical research in a multihospital environment. eardap can be characterized as terminology-based. Main advantage of our approach is the extensibility by new items and new research questions. Once the definition of items for a research question is finished, a consistent, corresponding database can be created without any informatics skills. Our experiences in pediatric oncology in Germany have shown the applicability of eardap. The functions of our core system were in routine clinical use in several hospitals. We validated the terminology management system (TMS) and the module generation tool with the basic data set of pediatric oncology. The multiple usability depends mainly on the quality of item planning in the TMS. High quality harmonization will lead to a higher amount of multiply used data. When using eardap, special emphasis is to be placed on interfaces to local hospital information systems and data security issues.

CBCT evaluation of multiple idiopathic internal resorptions in permanent molars: case report.

PubMed

Kalender, Atakan; Oztan, Meltem D; Basmaci, Fatma; Aksoy, Umut; Orhan, Kaan

2014-04-16

Internal inflammatory root resorption is a rare condition in permanent teeth, which requires the presence of necrotic and infected pulp tissue within the coronal portion of the root canal system as well as inflamed pulp tissue apical to the resorptive defect. The aetiology of internal root resorption is not completely understandable, trauma and chronic pulpitis are considered the main risk factors. We report a rare case of the multiple idiopathic resorption in the permanent maxillary and mandibular molars in a healthy 33-year-old female patient. In addition to clinical examination the patient was imaged using conventional radiography techniques and cone beam computed tomography (CBCT).The patient had recurrent throbbing pain in her # 46. The radiographic examination including "panoramic radiography and CBCT" revealed that radiographic evidence of internal resorption in #37 #36 #35 #34 #33 #47 #46 #45 #44 #43 #16 #15 #14 #13 and also including in unerupted #17, #26, #27, #28 teeth. The definitive diagnosis was made with the histopathological examination of the extracted tooth. Internal root resorption is a rare clinical process that should be examined using different radiographic modalities. CBCT seems to be useful in evaluation of the lesions with superior diagnostic performance.

Multiple Sclerosis and Subsequent Human Immunodeficiency Virus Infection: A Case with the Rare Comorbidity, Focus on Novel Treatment Issues and Review of the Literature.

PubMed

Skarlis, Charalampos; Gontika, Maria; Katsavos, Serafeim; Velonakis, Giorgios; Toulas, Panagiotis; Anagnostouli, Maria

2017-01-01

The comorbidity between Multiple Sclerosis (MS) and Human Immunodeficiency Virus (HIV) infection is particularly rare. Only a few cases of comorbidity of Clinically Definite(CD)-MS and HIV have been documented worldwide, while the potential beneficial role of antiretroviral therapy regarding MS activity has long been an area of debate. We present a 36-year old male, bearing a diagnosis of CD-MS for twelve years. He had been treated for ten years with interferon-beta-1b, when he voluntarily discontinued therapy, claiming clinical stability. One year later he was diagnosed positive for HIV and he started and continued only on efavirenz/emricitabine/tenofovir-disoproxil fumarate (ATRIPLA®), remaining relapse-free until today. This fact, in combination with the unique pharmaceutical composition of the drug, which contains a component similar to a newly-approved agent for MS, dimethyl fumarate, prompted us to review the literature regarding this rare comorbidity and to suggest that the role of the antiretroviral therapy should be further explored in MS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Cormorbidity in multiple sclerosis and its therapeutic approach].

PubMed

Estruch, Bonaventura Casanova

2014-12-01

Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients' health status helps to improve quality of life. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Energy Density, Energy Intake, and Body Weight Regulation in Adults12345

PubMed Central

Karl, J. Philip; Roberts, Susan B.

2014-01-01

The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight. PMID:25398750

The Child with Recurrent Mycobacterial Disease.

PubMed

Reed, Brian; Dolen, William K

2018-06-23

Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1. Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations. If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation.

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

PubMed

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

34 CFR 377.5 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., multiple sclerosis, muscular dystrophy, musculo-skeletal disorders, neurological disorders (including... rehabilitation can be expected to require multiple vocational rehabilitation services over an extended period of...

34 CFR 377.5 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., multiple sclerosis, muscular dystrophy, musculo-skeletal disorders, neurological disorders (including... rehabilitation can be expected to require multiple vocational rehabilitation services over an extended period of...

34 CFR 377.5 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., multiple sclerosis, muscular dystrophy, musculo-skeletal disorders, neurological disorders (including... rehabilitation can be expected to require multiple vocational rehabilitation services over an extended period of...

34 CFR 377.5 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., multiple sclerosis, muscular dystrophy, musculo-skeletal disorders, neurological disorders (including... rehabilitation can be expected to require multiple vocational rehabilitation services over an extended period of...

Evaluating Candidate Principal Surrogate Endpoints

PubMed Central

Gilbert, Peter B.; Hudgens, Michael G.

2009-01-01

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection. PMID:18363776

Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.

PubMed

Schulman, S; Angerås, U; Bergqvist, D; Eriksson, B; Lassen, M R; Fisher, W

2010-01-01

The definition of major bleeding varies between studies on surgical patients, particularly regarding the criteria for surgical wound-related bleeding. This diversity contributes to the difficulties in comparing data between trials. The Scientific and Standardization Committee (SSC), through its subcommittee on Control of Anticoagulation, of the International Society on Thrombosis and Haemostasis has previously published a recommendation for a harmonized definition of major bleeding in non-surgical studies. That definition has been adopted by the European Medicines Agency and is currently used in several non-surgical trials. A preliminary proposal for a parallel definition for surgical studies was presented at the 54(th) Annual Meeting of the SSC in Vienna, July 2008. Based on those discussions and further consultations with European and North American surgeons with experience from clinical trials a definition has been developed that should be applicable to all agents that interfere with hemostasis. The definition and the text that follows have been reviewed and approved by relevant co-chairs of the subcommittee and by the Executive Committee of the SSC. The intention is to seek approval of this definition from the regulatory authorities to enhance its incorporation into future clinical trial protocols.

Automatic segmentation of male pelvic anatomy on computed tomography images: a comparison with multiple observers in the context of a multicentre clinical trial.

PubMed

Geraghty, John P; Grogan, Garry; Ebert, Martin A

2013-04-30

This study investigates the variation in segmentation of several pelvic anatomical structures on computed tomography (CT) between multiple observers and a commercial automatic segmentation method, in the context of quality assurance and evaluation during a multicentre clinical trial. CT scans of two prostate cancer patients ('benchmarking cases'), one high risk (HR) and one intermediate risk (IR), were sent to multiple radiotherapy centres for segmentation of prostate, rectum and bladder structures according to the TROG 03.04 "RADAR" trial protocol definitions. The same structures were automatically segmented using iPlan software for the same two patients, allowing structures defined by automatic segmentation to be quantitatively compared with those defined by multiple observers. A sample of twenty trial patient datasets were also used to automatically generate anatomical structures for quantitative comparison with structures defined by individual observers for the same datasets. There was considerable agreement amongst all observers and automatic segmentation of the benchmarking cases for bladder (mean spatial variations < 0.4 cm across the majority of image slices). Although there was some variation in interpretation of the superior-inferior (cranio-caudal) extent of rectum, human-observer contours were typically within a mean 0.6 cm of automatically-defined contours. Prostate structures were more consistent for the HR case than the IR case with all human observers segmenting a prostate with considerably more volume (mean +113.3%) than that automatically segmented. Similar results were seen across the twenty sample datasets, with disagreement between iPlan and observers dominant at the prostatic apex and superior part of the rectum, which is consistent with observations made during quality assurance reviews during the trial. This study has demonstrated quantitative analysis for comparison of multi-observer segmentation studies. For automatic segmentation algorithms based on image-registration as in iPlan, it is apparent that agreement between observer and automatic segmentation will be a function of patient-specific image characteristics, particularly for anatomy with poor contrast definition. For this reason, it is suggested that automatic registration based on transformation of a single reference dataset adds a significant systematic bias to the resulting volumes and their use in the context of a multicentre trial should be carefully considered.

Clinical case review: a method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia.

PubMed

Puumalainen, Taneli; Quiambao, Beatriz; Abucejo-Ladesma, Erma; Lupisan, Socorro; Heiskanen-Kosma, Tarja; Ruutu, Petri; Lucero, Marilla G; Nohynek, Hanna; Simoes, Eric A F; Riley, Ian

2008-07-21

The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. ISRCTN62323832.

ASAS definition for sacroiliitis on MRI in SpA: applicable to children?

PubMed

Herregods, Nele; Dehoorne, Joke; Van den Bosch, Filip; Jaremko, Jacob Lester; Van Vlaenderen, Joke; Joos, Rik; Baraliakos, Xenofon; Varkas, Gaëlle; Verstraete, Koenraad; Elewaut, Dirk; Jans, Lennart

2017-04-11

The Assessment of Spondyloarthritis International Society (ASAS) definition for a 'positive' Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA). Two pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to gold-standard clinical diagnosis of JSpA. Additionally, MRI were scored according to'adapted' ASAS definitions including other features of sacroiliitis on MRI. JSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%. The adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice.

Acute respiratory distress syndrome 40 years later: time to revisit its definition.

PubMed

Phua, Jason; Stewart, Thomas E; Ferguson, Niall D

2008-10-01

Acute respiratory distress syndrome is a common disorder associated with significant mortality and morbidity. The aim of this article is to critically evaluate the definition of acute respiratory distress syndrome and examine the impact the definition has on clinical practice and research. Articles from a MEDLINE search (1950 to August 2007) using the Medical Subject Heading respiratory distress syndrome, adult, diagnosis, limited to the English language and human subjects, their relevant bibliographies, and personal collections, were reviewed. The definition of acute respiratory distress syndrome is important to researchers, clinicians, and administrators alike. It has evolved significantly over the last 40 years, culminating in the American-European Consensus Conference definition, which was published in 1994. Although the American-European Consensus Conference definition is widely used, it has some important limitations that may impact on the conduct of clinical research, on resource allocation, and ultimately on the bedside management of such patients. These limitations stem partially from the fact that as defined, acute respiratory distress syndrome is a heterogeneous entity and also involve the reliability and validity of the criteria used in the definition. This article critically evaluates the American-European Consensus Conference definition and its limitations. Importantly, it highlights how these limitations may contribute to clinical trials that have failed to detect a potential true treatment effect. Finally, recommendations are made that could be considered in future definition modifications with an emphasis on the significance of accurately identifying the target population in future trials and subsequently in clinical care. How acute respiratory distress syndrome is defined has a significant impact on the results of randomized, controlled trials and epidemiologic studies. Changes to the current American-European Consensus Conference definition are likely to have an important role in advancing the understanding and management of acute respiratory distress syndrome.

A unified procedure for meta-analytic evaluation of surrogate end points in randomized clinical trials

PubMed Central

Dai, James Y.; Hughes, James P.

2012-01-01

The meta-analytic approach to evaluating surrogate end points assesses the predictiveness of treatment effect on the surrogate toward treatment effect on the clinical end point based on multiple clinical trials. Definition and estimation of the correlation of treatment effects were developed in linear mixed models and later extended to binary or failure time outcomes on a case-by-case basis. In a general regression setting that covers nonnormal outcomes, we discuss in this paper several metrics that are useful in the meta-analytic evaluation of surrogacy. We propose a unified 3-step procedure to assess these metrics in settings with binary end points, time-to-event outcomes, or repeated measures. First, the joint distribution of estimated treatment effects is ascertained by an estimating equation approach; second, the restricted maximum likelihood method is used to estimate the means and the variance components of the random treatment effects; finally, confidence intervals are constructed by a parametric bootstrap procedure. The proposed method is evaluated by simulations and applications to 2 clinical trials. PMID:22394448

Clinical and Magnetic Resonance Imaging Findings of Neurotoxocariasis.

PubMed

Sánchez, Sofia S; García, Hector H; Nicoletti, Alessandra

2018-01-01

Human toxocariasis is one of the most prevalent helminthiases worldwide. Toxocara canis larvae can cross the blood-brain barrier leading to the neurotoxocariasis. The clinical presentation consists of a wide spectrum of neurological manifestations, but asymptomatic infection is probably common. Neurotoxocariasis is not a frequent diagnosis probably due to the non-specific nature of its symptoms as well as the lack of confirmatory diagnostic tests. Diagnosis of neurotoxocariasis is based on the presence of a high titer of anti- Toxocara antibody in the cerebrospinal fluid or in the serum, presence of eosinophilia in the serum or cerebrospinal fluid, and clinical and radiological improvement after anthelmintic therapy; however, universally accepted diagnostic criteria are lacking. Magnetic resonance imaging (MRI) findings include single or multiple, subcortical, cortical or white matter hyperintense lesions, best visualized on FLAIR and T2-weighted imaging, and usually isointense or hypointense on T1. These imaging findings are suggestive but not specific to neurotoxocariasis. Definitive diagnosis is made by histological confirmation, but it is rarely followed. This review provides an overview of the clinical manifestations, management options, and MRI findings of neurotoxocariasis.

Clinical and Magnetic Resonance Imaging Findings of Neurotoxocariasis

PubMed Central

Sánchez, Sofia S.; García, Hector H.; Nicoletti, Alessandra

2018-01-01

Human toxocariasis is one of the most prevalent helminthiases worldwide. Toxocara canis larvae can cross the blood–brain barrier leading to the neurotoxocariasis. The clinical presentation consists of a wide spectrum of neurological manifestations, but asymptomatic infection is probably common. Neurotoxocariasis is not a frequent diagnosis probably due to the non-specific nature of its symptoms as well as the lack of confirmatory diagnostic tests. Diagnosis of neurotoxocariasis is based on the presence of a high titer of anti-Toxocara antibody in the cerebrospinal fluid or in the serum, presence of eosinophilia in the serum or cerebrospinal fluid, and clinical and radiological improvement after anthelmintic therapy; however, universally accepted diagnostic criteria are lacking. Magnetic resonance imaging (MRI) findings include single or multiple, subcortical, cortical or white matter hyperintense lesions, best visualized on FLAIR and T2-weighted imaging, and usually isointense or hypointense on T1. These imaging findings are suggestive but not specific to neurotoxocariasis. Definitive diagnosis is made by histological confirmation, but it is rarely followed. This review provides an overview of the clinical manifestations, management options, and MRI findings of neurotoxocariasis. PMID:29472889

The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study.

PubMed

Freedman, Mark S; Leist, Thomas P; Comi, Giancarlo; Cree, Bruce Ac; Coyle, Patricia K; Hartung, Hans-Peter; Vermersch, Patrick; Damian, Doris; Dangond, Fernando

2017-01-01

Multiple sclerosis (MS) diagnostic criteria have changed since the ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria. The objective of this paper is to assess the effect of cladribine tablets in patients with a first clinical demyelinating attack fulfilling newer criteria (McDonald 2010) for MS vs CIS. A post hoc analysis for subgroups of patients retrospectively classified as fulfilling or not fulfilling newer criteria at the first clinical demyelinating attack was conducted. Cladribine tablets 3.5 mg/kg ( n  = 68) reduced the risk of next attack or three-month confirmed Expanded Disability Status Scale (EDSS) worsening by 74% vs placebo ( n  = 72); p  = 0.0009 in patients meeting newer criteria for MS at baseline. Cladribine tablets 5.25 mg/kg ( n  = 83) reduced the risk of next attack or three-month confirmed EDSS worsening by 37%, but nominal significance was not reached ( p  = 0.14). In patients who were still CIS after applying newer criteria, cladribine tablets 3.5 mg/kg ( n  = 138) reduced the risk of conversion to clinically definite multiple sclerosis (CDMS) by 63% vs placebo ( n  = 134); p  = 0.0003. Cladribine tablets 5.25 mg/kg ( n  = 121) reduced the risk of conversion by 75% vs placebo ( n  = 134); p  < 0.0001. Regardless of the criteria used to define CIS or MS, 3.5 mg/kg cladribine tablets are effective in patients with a first clinical demyelinating attack. ClinicalTrials.gov registration: The ORACLE-MS study (NCT00725985).

Managing serious clinical deterioration in a tertiary hospital in Hong Kong: from indicators development to multiple measures in reducing the rates.

PubMed

Ho, Jasperine Ka Yee; Lee, Quinnie; Lam, Jaden Chun Ho; Tang, Kam Shing

2017-06-01

Timely detection and management of acutely deteriorating patients can save lives. Tuen Mun Hospital (TMH), a 1800-bed acute tertiary hospital serving more than 1.06 million populations in Hong Kong, is exploring to quantitatively monitor serious clinical deterioration (SCD) and uses it to guide patient care improvement initiatives. Literature review on definition and measurement of SCD was conducted. Monthly SCD rates of TMH were first calculated according to the published methodology and benchmarked against those of international centres. A refined composite clinical indicator good for local use was compiled. In the second phase, p-control charts of SCD have been plotted based on cumulative data. TMH's performance was comparable with that of international centres. SCD on p-control charts has been plotting since January 2013. There were peaks in all 4 SCD rates during the winter surge period in 2013-2014. In the third phase, multiple measures have been taking to reduce the SCD rates including targeting the 3 main factors of winter surge situation. We are delighted to observe that the pattern did not repeat in the rate of cardiac arrest without do not attempt cardiopulmonary resuscitation (DNACPR) and rate of death without DNACPR in the same period in 2014-2015. SCD becomes a clinical governance tool to monitor the performance of clinical teams in treating acutely deteriorating patients in TMH. Any abnormal patterns or indications of special cause variations in the control charts would alert leaders to look for root causes of special cause variations and manage accordingly. We hope that this project will extend to corporate level and become a sustainable clinical indicator to guide audits, quality improvement initiatives and strategic planning. © 2016 John Wiley & Sons, Ltd.

Development of Responder Definitions for Fibromyalgia Clinical Trials

PubMed Central

Arnold, Lesley M.; Williams, David A.; Hudson, James I.; Martin, Susan A.; Clauw, Daniel J.; Crofford, Leslie J.; Wang, Fujun; Emir, Birol; Lai, Chinglin; Zablocki, Rong; Mease, Philip J.

2011-01-01

Objective To develop responder definitions for fibromyalgia clinical trials using key symptom and functional domains. Methods 24 candidate responder definitions were developed by expert consensus and evaluated in 12 randomized, placebo-controlled fibromyalgia trials of 4 medications. For each definition, treatment effects of the medication compared with placebo were analyzed using the Cochran-Mantel-Haenszel test or Chi Square test. A meta-analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo. Results Two definitions performed best in the analyses. Both definitions included ≥ 30% reduction in pain and ≥ 10% improvement in physical function. They differed in that one (FM30 short version) included ≥ 30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥ 30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥ 15% for each medication and significantly greater than placebo. The risk ratio favoring drug over placebo (95% CI) in the pooled analysis for the FM30 short version was 1.50 (1.24, 1.82), P ≤ 0.0001; the FM30 long version was 1.60 (1.31, 1.96), P ≤ 0.00001. Conclusion Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for fibromyalgia clinical trials that include assessments of key symptom and functional domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of fibromyalgia. PMID:21953205

The role of speed versus working memory in predicting learning new information in multiple sclerosis.

PubMed

Chiaravalloti, Nancy D; Stojanovic-Radic, Jelena; DeLuca, John

2013-01-01

The most common cognitive impairments in multiple sclerosis (MS) have been documented in specific domains, including new learning and memory, working memory, and information processing speed. However, little attempt has been made to increase our understanding of their relationship to one another. While recent studies have shown that processing speed impacts new learning and memory abilities in MS, the role of working memory in this relationship has received less attention. The present study examines the relative contribution of impaired working memory versus processing speed in new learning and memory functions in MS. Participants consisted of 51 individuals with clinically definite MS. Participants completed two measures of processing speed, two measures of working memory, and two measures of episodic memory. Data were analyzed via correlational and multiple regression analysis. Results indicate that the variance in new learning abilities in this sample was primarily associated with processing speed, with working memory exerting much less of an influence. Results are discussed in terms of the role of cognitive rehabilitation of new learning and memory abilities in persons with MS.

Enhancing clinical decision making: development of a contiguous definition and conceptual framework.

PubMed

Tiffen, Jennifer; Corbridge, Susan J; Slimmer, Lynda

2014-01-01

Clinical decision making is a term frequently used to describe the fundamental role of the nurse practitioner; however, other terms have been used interchangeably. The purpose of this article is to begin the process of developing a definition and framework of clinical decision making. The developed definition was "Clinical decision making is a contextual, continuous, and evolving process, where data are gathered, interpreted, and evaluated in order to select an evidence-based choice of action." A contiguous framework for clinical decision making specific for nurse practitioners is also proposed. Having a clear and unique understanding of clinical decision making will allow for consistent use of the term, which is relevant given the changing educational requirements for nurse practitioners and broadening scope of practice. Copyright © 2014 Elsevier Inc. All rights reserved.

What Is College and Career Readiness? A Summary of State Definitions. Bulletin, Issue 22

ERIC Educational Resources Information Center

Conforti, Peter A.

2013-01-01

This paper outlines each state's definition of college and career readiness and shows whether they associate with the Common Core State Standards Initiative (CCSSI), ACT College and Career Readiness System (ACCRS), or both. The general definition that emerges can not only facilitate interstate discussions on multiple levels, but also provide…

Satellite lesions in congenital melanocytic nevi--time for a change of name.

PubMed

Kinsler, Veronica

2011-01-01

The term "satellite lesions" is used in many conditions in dermatology, generally to describe smaller lesions near the edges of a principal lesion. An online medical dictionary gives the definition "a smaller lesion accompanying a main one and situated nearby," and this can apply both macroscopically and microscopically. The implication is that the smaller lesions have spread from the parent lesion. Given this definition and usual understanding of the term its use is not apt in the case of congenital melanocytic nevi (CMN). In the vast majority of cases where the patient is said to have satellite lesions these are not restricted to the area around or near the edge of the principal lesion, and are not necessarily significantly smaller. It seems likely that the early use of the term in this condition is an adaptation of the established and correct use in the context of melanoma. Not only is the term not apt clinically but has no known etiological basis. This leaves us with the question of what to call these lesions in cases of CMN. This proposal is to categorize cases into single or multiple CMN, where multiple is 2 or more nevi of any size at birth. An accurate count or good estimate of the number of lesions at birth should also be recorded, and the largest lesion classified as usual with respect to projected adult size. © 2011 Wiley Periodicals, Inc.

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

PubMed Central

Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

2015-01-01

Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed. PMID:26581079

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

PubMed

Azar, Marleine; Riehm, Kira E; McKay, Dean; Thombs, Brett D

2015-01-01

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.

Better infrastructure for critical care trials: nomenclature, etymology, and informatics.

PubMed

Singh, Jeffrey M; Ferguson, Niall D

2009-01-01

The goals of this review article are to review the importance and value of standardized definitions in clinical research, as well as to propose the necessary tools and infrastructure needed to advance nosology and medial taxonomy to improve the quality of clinical trials in the field of critical care. We searched MEDLINE for relevant articles, reviewed those selected and their reference lists, and consulted personal files for relevant information. When the pathobiology of diseases is well understood, standard disease definitions can be extremely specific and precise; however, when the pathobiology of the disease is less well understood or more complex, biological markers may not be diagnostically useful or even available. In these cases, syndromic definitions effectively classify and group illnesses with similar symptoms and clinical signs. There is no clear gold standard for the diagnosis of many clinical entities in the intensive care unit, including notably both acute respiratory distress syndrome and sepsis. There are several types of consensus methods that can be used to explicate the judgmental approach that is often needed in these cases, including interactive or consensus groups, the nominal group technique, and the Delphi technique. Ideally, the definition development process will create clear and unambiguous language in which each definition accurately reflects the current understanding of the disease state. The development, implementation, evaluation, revision, and reevaluation of standardized definitions are keys for advancing the quality of clinical trials in the critical care arena.

Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis.

PubMed

Teunissen, Charlotte; Menge, Til; Altintas, Ayse; Álvarez-Cermeño, José C; Bertolotto, Antonio; Berven, Frode S; Brundin, Lou; Comabella, Manuel; Degn, Matilde; Deisenhammer, Florian; Fazekas, Franz; Franciotta, Diego; Frederiksen, Jette L; Galimberti, Daniela; Gnanapavan, Sharmilee; Hegen, Harald; Hemmer, Bernhard; Hintzen, Rogier; Hughes, Steve; Iacobaeus, Ellen; Kroksveen, Ann C; Kuhle, Jens; Richert, John; Tumani, Hayrettin; Villar, Luisa M; Drulovic, Jelena; Dujmovic, Irena; Khalil, Michael; Bartos, Ales

2013-11-01

The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.

Emergency cesarean section and the 30-minute rule: definitions.

PubMed

Schauberger, Charles W; Chauhan, Suneet P

2009-03-01

We explored the role that lack of a standard definition and heterogeneity in patient selection criteria in the literature might have on the apparent inability to routinely begin an emergency cesarean section in less than 30 minutes. A review of the literature on emergency cesarean delivery was performed. Although there are some similarities in definitions and the criteria used for patient selection in multiple studies, the variability in the definitions could be responsible for some of the apparent timeliness performance deficiency in the literature. A standard definition and directions for future research are suggested.

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.

PubMed

Bines, Julie E; Liem, Nguyen Thanh; Justice, Frances; Son, Tran Ngoc; Carlin, John B; de Campo, Margaret; Jamsen, Kris; Mulholland, Kim; Barnett, Peter; Barnes, Graeme L

2006-07-01

To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged<2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged<2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.

Confirmed clinical case of chronic kidney disease of nontraditional causes in agricultural communities in Central America: a case definition for surveillance.

PubMed

Ferreiro, Alejandro; Álvarez-Estévez, Guillermo; Cerdas-Calderón, Manuel; Cruz-Trujillo, Zulma; Mena, Elio; Reyes, Marina; Sandoval-Diaz, Mabel; Sánchez-Polo, Vicente; Valdés, Régulo; Ordúnez, Pedro

2016-11-01

Over the last 20 years, many reports have described an excess of cases of chronic kidney disease (CKD) in the Pacific coastal area of Central America, mainly affecting male farmworkers and signaling a serious public health problem. Most of these cases are not associated with traditional risk factors for CKD, such as aging, diabetes mellitus, and hypertension. This CKD of nontraditional causes (CKDnT) might be linked to environmental and/or occupational exposure or working conditions, limited access to health services, and poverty. In response to a resolution approved by the Directing Council of the Pan American Health Organization (PAHO) in 2013, PAHO, the U.S. Centers for Disease Control and Prevention, and the Latin American Society of Nephrology and Hypertension (SLANH) organized a consultation process in order to expand knowledge on the epidemic of CKDnT and to develop appropriate surveillance instruments. The Clinical Working Group from SLANH was put in charge of finding a consensus definition of a confirmed clinical case of CKDnT. The resulting definition establishes mandatory criteria and exclusion criteria necessary for classifying a case of CKDnT. The definition includes a combination of universally accepted definitions of CKD and the main clinical manifestations of CKDnT. Based on the best available evidence, the Clinical Working Group also formulated general recommendations about clinical management that apply to any patient with CKDnT. Adhering to the definition of a confirmed clinical case of CKDnT and implementing it appropriately is expected to be a powerful instrument for understanding the prevalence of the epidemic, evaluating the results of interventions, and promoting appropriate advocacy and planning efforts.

Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance.

PubMed

Sontag, Marci K; Sarkar, Deboshree; Comeau, Anne M; Hassell, Kathryn; Botto, Lorenzo D; Parad, Richard; Rose, Susan R; Wintergerst, Kupper A; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F

2018-01-01

Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary's Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

Case Definitions for Conditions Identified by Newborn Screening Public Health Surveillance

PubMed Central

Sontag, Marci K.; Sarkar, Deboshree; Comeau, Anne M.; Hassell, Kathryn; Botto, Lorenzo D.; Parad, Richard; Rose, Susan R.; Wintergerst, Kupper A.; Smith-Whitley, Kim; Singh, Sikha; Yusuf, Careema; Ojodu, Jelili; Copeland, Sara; Hinton, Cynthia F.

2018-01-01

Newborn screening (NBS) identifies infants with rare conditions to prevent death or the onset of irreversible morbidities. Conditions on the Health and Human Services Secretary’s Recommended Uniform Screening Panel have been adopted by most state NBS programs, providing a consistent approach for identification of affected newborns across the United States. Screen-positive newborns are identified and referred for confirmatory diagnosis and follow-up. The designation of a clinically significant phenotype precursor to a clinical diagnosis may vary between clinical specialists, resulting in diagnostic variation. Determination of disease burden and birth prevalence of the screened conditions by public health tracking is made challenging by these variations. This report describes the development of a core group of new case definitions, along with implications, plans for their use, and links to the definitions that were developed by panels of clinical experts. These definitions have been developed through an iterative process and are piloted in NBS programs. Consensus public health surveillance case definitions for newborn screened disorders will allow for consistent categorization and tracking of short- and long-term follow-up of identified newborns at the local, regional, and national levels.

Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Warren, Bethany; Pankow, James S; Matsushita, Kunihiro; Punjabi, Naresh M; Daya, Natalie R; Grams, Morgan; Woodward, Mark; Selvin, Elizabeth

2017-01-01

No consensus on definitions of prediabetes exists among international organisations. Analysis of associations with different definitions and clinical complications can inform the comparative value of different prediabetes definitions. We compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA 1c , and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the associations of definitions with outcomes to provide a comparison of different definitions. We did a prospective cohort study of participants in the ARIC study who did not have diagnosed diabetes and who attended visit 2 (1990-92; n=10 844) and who attended visit 4 (1996-98; n=7194). ARIC participants were enrolled from four communities across the USA. Fasting glucose concentration and HbA 1c were measured at visit 2 and fasting glucose concentration and 2 h glucose concentration were measured at visit 4. We compared prediabetes definitions based on fasting glucose concentration (American Diabetes Association [ADA] fasting glucose concentration cutoff 5·6-6·9 mmol/L and WHO fasting glucose concentration cutoff 6·1-6·9 mmol/L), HbA 1c (ADA HbA 1c cutoff 5·7-6·4% [39-46 mmol/mol] and International Expert Committee [IEC] HbA 1c cutoff 6·0-6·4% [42-46 mmol/mol]), and 2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7·8-11·0 mmol/L). Prediabetes defined using the ADA fasting glucose concentration cutoff (prevalence 4112 [38%] of 10 844 people; 95% CI 37·0-38·8) was the most sensitive for major clinical outcomes, whereas using the ADA HbA 1c cutoff (2027 [19%] of 10 884 people; 18·0-19·4) and IEC HbA 1c cutoff (970 [9%] of 10 844 people; 8·4-9·5), and the WHO fasting glucose concentration cutoff (1213 [11%] of 10 844 people; 10·6-11·8) were more specific. After demographic adjustment, HbA 1c -based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality than did fasting glucose concentration-based definitions (all p<0·05). The C-statistic for incident chronic kidney disease was 0·636 for ADA fasting glucose concentration clinical categories and 0·640 for ADA HbA 1c clinical categories (difference -0·005, 95% CI -0·008 to -0·001). The C-statistics were 0·662 for ADA fasting glucose clinical concentration categories and 0·672 for ADA HbA 1c clinical categories for atherosclerotic cardiovascular disease, 0·701 for ADA fasting glucose concentration clinical categories and 0·722 for ADA HbA 1c clinical categories for peripheral arterial disease, and 0·683 for ADA fasting glucose concentration clinical categories and 0·688 for ADA HbA 1c clinical categories for all-cause mortality. Prediabetes defined using the ADA HbA 1c cutoff showed a significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared with prediabetes defined with glucose-based definitions. ADA fasting glucose concentration clinical categories, WHO fasting glucose concentration clinical categories, and ADA and WHO 2 h glucose concentrations clinical categories were not significantly different in terms of risk discrimination for chronic kidney disease, cardiovascular outcomes, or mortality outcomes. Our results suggest that prediabetes definitions using HbA 1c were more specific and provided modest improvements in risk discrimination for clinical complications. The definition of prediabetes using the ADA fasting glucose concentration cutoff was more sensitive overall. US National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Profiling Fast Healthcare Interoperability Resources (FHIR) of Family Health History based on the Clinical Element Models.

PubMed

Lee, Jaehoon; Hulse, Nathan C; Wood, Grant M; Oniki, Thomas A; Huff, Stanley M

2016-01-01

In this study we developed a Fast Healthcare Interoperability Resources (FHIR) profile to support exchanging a full pedigree based family health history (FHH) information across multiple systems and applications used by clinicians, patients, and researchers. We used previously developed clinical element models (CEMs) that are capable of representing the FHH information, and derived essential data elements including attributes, constraints, and value sets. We analyzed gaps between the FHH CEM elements and existing FHIR resources. Based on the analysis, we developed a profile that consists of 1) FHIR resources for essential FHH data elements, 2) extensions for additional elements that were not covered by the resources, and 3) a structured definition to integrate patient and family member information in a FHIR message. We implemented the profile using an open-source based FHIR framework and validated it using patient-entered FHH data that was captured through a locally developed FHH tool.

Cutaneous sarcoids in captive African lions associated with feline sarcoid-associated papillomavirus infection.

PubMed

Orbell, G M B; Young, S; Munday, J S

2011-11-01

Solitary and multiple cutaneous and mucocutaneous masses were identified in 5 of 24 captive African lions (Panthera leo) over a 6-month-period. All masses were surgically excised, and all were histologically similar to equine and feline sarcoids. DNA was extracted from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction amplified DNA sequences that had been previously detected in feline sarcoids and clinically normal bovine skin. All lions had been fed a diet that included bovine carcasses that had not been skinned. Since the cessation of feeding bovine carcasses with cutaneous lesions, no additional skin lesions have been observed within any of the lions. Herein is described the clinical, gross, and histopathological findings of sarcoids in 5 captive lions. As the causative papillomavirus most likely has a bovine definitive host, it is hypothesized that the lions were exposed to the virus by feeding on bovine carcasses with skin still attached.

[Chronic diarrhoea: Definition, classification and diagnosis].

PubMed

Fernández-Bañares, Fernando; Accarino, Anna; Balboa, Agustín; Domènech, Eugeni; Esteve, Maria; Garcia-Planella, Esther; Guardiola, Jordi; Molero, Xavier; Rodríguez-Luna, Alba; Ruiz-Cerulla, Alexandra; Santos, Javier; Vaquero, Eva

2016-10-01

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Metabolic syndrome pathophysiology and clinical presentation.

PubMed

Handelsman, Yehuda

2009-01-01

Metabolic syndrome is a relatively new definition, designed to help the health care practitioner to easily identify people at risk for the development of cardiovascular disease and diabetes. With the obesity epidemic, we are witnessing an epidemic of multiple-risk patients. Insulin resistance is the perceived pathophysiology of metabolic syndrome and defines its clinical presentation. Hypertension, dyslipedemia, polycystic ovarian syndrome, fatty liver disease, pre-diabetes, sleep and breathing disorder, certain cancers, and cognitive impairment are many of the presentations of the syndrome; patients with any of these conditions are at a high risk of developing cardiovascular disease and diabetes. The metabolic syndrome helps identify people at risk to allow early intervention for prevention. Lifestyle modification is the most important part of the management of people with the syndrome. Lately medications--though none approved by the U.S. Food and Drug Administration (FDA)--have been recommended by major medical societies when lifestyle modification is not enough or when it fails.

Overtraining Syndrome

PubMed Central

Kreher, Jeffrey B.; Schwartz, Jennifer B.

2012-01-01

Context: Fatigue and underperformance are common in athletes. Understanding overtraining syndrome (OTS) is helpful in the evaluation, management, and education of athletes. Evidence Acquisition: Relevant articles in English were searched with OVID (1948-2011) and PubMed using the following keywords: overtraining syndrome, overtraining, overreaching, unexplained underperformance, staleness, pathophysiology, management, treatment, evaluation. Bibliographies were reviewed for additional resources. Results: OTS appears to be a maladapted response to excessive exercise without adequate rest, resulting in perturbations of multiple body systems (neurologic, endocrinologic, immunologic) coupled with mood changes. Many hypotheses of OTS pathogenesis are reviewed, and a clinical approach to athletes with possible OTS (including history, testing, and prevention) is presented. Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS. PMID:23016079

Clinical Diabetes Centers of Excellence: A Model for Future Adult Diabetes Care.

PubMed

Draznin, Boris; Kahn, Peter A; Wagner, Nicole; Hirsch, Irl B; Korytkowski, Mary; Harlan, David M; McDonnell, Marie E; Gabbay, Robert A

2018-03-01

Although diabetes research centers are well defined by National Institutes of Health, there is no clear definition for clinical Diabetes Centers of Excellence (DCOEs). There are multiple clinical diabetes centers across the United States, some established with philanthropic funding; however, it is not clear what defines a DCOE from a clinical perspective and what the future will be for these centers. In this Perspective we propose a framework to guide advancement for DCOEs. With the shift toward value-based purchasing and reimbursement and away from fee for service, defining the procedures for broader implementation of DCOEs as a way to improve population health and patient care experience (including quality and satisfaction) and reduce health care costs becomes critically important. It is prudent to implement new financial systems for compensating diabetes care that may not be provided by fiscally constrained private and academic medical centers. We envision that future clinical DCOEs would be composed of a well-defined infrastructure and six domains or pillars serving as the general guiding principles for developing expertise in diabetes care that can be readily demonstrated to stakeholders, including health care providers, patients, payers, and government agencies.

The molecular biology of soft-tissue sarcomas and current trends in therapy.

PubMed

Quesada, Jorge; Amato, Robert

2012-01-01

Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review.

PubMed

Bonnett, Laura Jayne; Ken-Dror, Gie; Davies, Geraint Rhys

2018-02-21

Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required. A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Of 248 included studies, 229 considered "on-treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of "intensive" and "continuation" phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome. Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

Soliciting Strategies for Developing Cell-Based Reference Materials to Advance Mesenchymal Stromal Cell Research and Clinical Translation

PubMed Central

Viswanathan, Sowmya; Keating, Armand; Deans, Robert; Hematti, Peiman; Prockop, Darwin; Stroncek, David F.; Stacey, Glyn; Weiss, Dan J.; Mason, Christopher

2014-01-01

The mesenchymal stromal cell (MSC) field continues to rapidly progress with a number of clinical trials initiated and completed, with some reported successes in multiple clinical indications, and a growing number of companies established. The field, nevertheless, faces several challenges. Persistent issues include the definition of a MSC and comparability between MSC preparations. This is because of inherent cell heterogeneity, the absence of markers that are unique to MSCs, and the difficulty in precisely defining them by developmental origin. Differences in the properties of MSCs also depend on the site of tissue harvest, phenotypic and genotypic characteristics of the donor and the isolation, and storage and expansion methods used. These differences may be sufficient to ensure that attributes of the final MSC product could differ in potentially significant ways. Since there are currently no gold standards, we propose using a reference material to establish methods of comparability among MSC preparations. We suggest four possible “ruler scenarios” and a method for global distribution. We further suggest that critical to establishing a reference material is the need to define protocols for comparing cells. The main purpose of this article is to solicit input in establishing a consensus-based comparison. A comparative approach will be critical to all stages of translation to better clarify mechanisms of MSC actions, define an optimal cell manufacturing process, ensure best practice clinical investigations, extend the use of an MSC product for new indications, protect an MSC product from imitators, and develop uniform reimbursement policies. Importantly, a reference material may enable a consensus on a practical definition of MSCs. PMID:24422625

Mouse Models of Genomic Syndromes as Tools for Understanding the Basis of Complex Traits: An Example with the Smith-Magenis and the Potocki-Lupski Syndromes

PubMed Central

Carmona-Mora, P; Molina, J; Encina, C.A; Walz, K

2009-01-01

Each human's genome is distinguished by extra and missing DNA that can be “benign” or powerfully impact everything from development to disease. In the case of genomic disorders DNA rearrangements, such as deletions or duplications, correlate with a clinical specific phenotype. The clinical presentations of genomic disorders were thought to result from altered gene copy number of physically linked dosage sensitive genes. Genomic disorders are frequent diseases (~1 per 1,000 births). Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders, associated with a deletion and a duplication, of 3.7 Mb respectively, within chromosome 17 band p11.2. This region includes 23 genes. Both syndromes have complex and distinctive phenotypes including multiple congenital and neurobehavioral abnormalities. Human chromosome 17p11.2 is syntenic to the 32-34 cM region of murine chromosome 11. The number and order of the genes are highly conserved. In this review, we will exemplify how genomic disorders can be modeled in mice and the advantages that such models can give in the study of genomic disorders in particular and gene copy number variation (CNV) in general. The contributions of the SMS and PTLS animal models in several aspects ranging from more specific ones, as the definition of the clinical aspects of the human clinical spectrum, the identification of dosage sensitive genes related to the human syndromes, to the more general contributions as the definition of genetic locus impacting obesity and behavior and the elucidation of general mechanisms related to the pathogenesis of gene CNV are discussed. PMID:19949547

Persistent pain and comorbidity among Operation Enduring Freedom/Operation Iraqi Freedom/operation New Dawn veterans.

PubMed

Higgins, Diana M; Kerns, Robert D; Brandt, Cynthia A; Haskell, Sally G; Bathulapalli, Harini; Gilliam, Wesley; Goulet, Joseph L

2014-05-01

Chronic pain is a significant concern for the Veterans Health Administration (VHA), with chronic pain conditions among those most frequently reported by Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans. The current study examined VHA electronic medical record data to examine variation in demographics and high prevalence and high impact medical and mental health conditions in order to characterize the differences between patients with persistent pain and no pain. A conservative operational definition of chronic or "persistent pain" based on multiple indicators of pain (i.e., pain intensity ratings, prescription opioids, pain clinic visits, International Classification of Diseases, Ninth Revision codes) was employed. Analyses included the entire roster of longitudinal clinical data on OEF/OIF/OND veterans who used VHA care to compare those with persistent pain with those with no clinical evidence of pain. Results of logistic regression models suggest that sex, race, education, military variables, body mass index (BMI), traumatic brain injury (TBI), and mental health conditions, but not age, reliably discriminate the two groups. Those with persistent pain were more likely to be Black, female, on active duty, enlisted, Army service members, have a high school education or less, and have diagnoses of mood disorders, post-traumatic stress disorder, substance use disorders, anxiety disorders, TBI, and have a BMI consistent with overweight and obesity. The operational definition of chronic pain used in this study may have research implications for examining predictors of incident and chronic pain. These data have important clinical implications in that addressing comorbid conditions of persistent pain may improve adaptive coping and functioning in these patients. Wiley Periodicals, Inc.

How to use PET/CT in the evaluation of response to radiotherapy.

PubMed

Decazes, Pierre; Thureau, Sébastien; Dubray, Bernard; Vera, Pierre

2018-06-01

Radiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI.

A Comparison of Bridging Methods in the Analysis of NAEP Trends with the New Race Subgroup Definitions

ERIC Educational Resources Information Center

Meyer, J. Patrick; Setzer, J. Carl

2009-01-01

Recent changes to federal guidelines for the collection of data on race and ethnicity allow respondents to select multiple race categories. Redefining race subgroups in this manner poses problems for research spanning both sets of definitions. NAEP long-term trends have used the single-race subgroup definitions for over thirty years. Little is…

What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review.

PubMed

Lawal, Adegboyega K; Rotter, Thomas; Kinsman, Leigh; Machotta, Andreas; Ronellenfitsch, Ulrich; Scott, Shannon D; Goodridge, Donna; Plishka, Christopher; Groot, Gary

2016-02-23

Clinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refinement of an operational definition for CPW research and proposes an operational definition for the future syntheses of CPWs literature. Following the approach proposed by Kinsman et al. (BMC Medicine 8(1):31, 2010) and Wieland et al. (Alternative Therapies in Health and Medicine 17(2):50, 2011), we used a four-stage process to generate a five criteria checklist for the definition of CPWs. We refined the operational definition, through consensus, merging two of the checklist's criteria, leading to a more inclusive criterion for accommodating CPW studies conducted in various healthcare settings. The following four criteria for CPW operational definition, derived from the refinement process described above, are (1) the intervention was a structured multidisciplinary plan of care; (2) the intervention was used to translate guidelines or evidence into local structures; (3) the intervention detailed the steps in a course of treatment or care in a plan, pathway, algorithm, guideline, protocol or other 'inventory of actions' (i.e. the intervention had time-frames or criteria-based progression); and (4) the intervention aimed to standardize care for a specific population. An intervention meeting all four criteria was considered to be a CPW. The development of operational definitions for complex interventions is a useful approach to appraise and synthesize evidence for policy development and quality improvement.

Standardized definitions and clinical endpoints in carotid artery and supra-aortic trunk revascularization trials.

PubMed

Nedeltchev, Krassen; Pattynama, Peter M; Biaminoo, Giancarlo; Diehm, Nicolas; Jaff, Michael R; Hopkins, L Nelson; Ramee, Stephen; van Sambeek, Marc; Talen, Aly; Vermassen, Frank; Cremonesi, Alberto

2010-09-01

Endovascular therapy has emerged as a promising alternative to open surgery for stroke prevention in patients with obstructive disease of the supra-aortic arteries. Although most previous studies have used similar safety and efficacy endpoints, differences in definitions, timing of assessments, and standards of reporting have hampered direct comparisons across various trials. The DEFINE group, an informal collaboration of multidisciplinary physicians, involved in the therapy of patients with obstructive disease of the supra-aortic arteries in Europe and the United States reviewed the current literature and, after extensive correspondence and meetings, proposed the definitions outlined in the present manuscript. Three meetings including all authors of the manuscript, along with representatives of the United States Food and Drug Administration (FDA) and commercial device manufacturers were held in Barcelona, Spain, in May 2008, in Munich, Germany, in July 2008, and in New York in November 2008. The proposed definitions encompass baseline clinical and anatomic characteristics, clinical and radiologic outcomes, complications, standards of reporting, and timing of assessment. Considering the broad consensus between the multidisciplinary scientific members and the regulatory authorities, the proposed definitions are expected to find adoption in future clinical investigations. These definitions can be applied to both endovascular and open surgery trials and will allow reliable comparisons between these two revascularization methods.

Case definition for clinical and subclinical bacterial kidney disease (BKD) in Atlantic Salmon (Salmo salar L.) in New Brunswick, Canada.

PubMed

Boerlage, A S; Stryhn, H; Sanchez, J; Hammell, K L

2017-03-01

Bacterial kidney disease (BKD) is considered an important cause of loss in salmon aquaculture in Atlantic Canada. Causative agent of BKD is the Gram-positive bacteria Renibacterium salmoninarum. Infected salmon are often asymptomatic (subclinical infection), and the disease is considered chronic. One of the challenges in quantifying information from farm production and health records is the application of a standardized case definition. Case definitions for farm-level and cage-level clinical and subclinical BKD were developed using retrospective longitudinal data from aquaculture practices in New Brunswick, Canada, combining (i) industry records of weekly production data including mortalities, (ii) field observations for BKD using reports of veterinarians and/or fish health technicians, (iii) diagnostic submissions and test results and (iv) treatments used to control BKD. Case definitions were evaluated using veterinarians' expert judgements as reference standard. Eighty-nine and 66% of sites and fish groups, respectively, were associated with BKD at least once. For BKD present (subclinical or clinical), sensitivity and specificity of the case definition were 75-100% varying between event, fish group, site cycle and level (site pen). For clinical BKD, sensitivities were 29-64% and specificities 91-100%. Industry data can be used to develop sensitive case definitions. © 2016 John Wiley & Sons Ltd.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection

PubMed Central

Qasmieh, Saba; Mounts, Anthony Wayne; Alexander, Burmaa; Besselaar, Terry; Briand, Sylvie; Brown, Caroline; Clark, Seth; Dueger, Erica; Gross, Diane; Hauge, Siri; Hirve, Siddhivinayak; Jorgensen, Pernille; Katz, Mark A; Mafi, Ali; Malik, Mamunur; McCarron, Margaret; Meerhoff, Tamara; Mori, Yuichiro; Mott, Joshua; Olivera, Maria Teresa da Costa; Ortiz, Justin R; Palekar, Rakhee; Rebelo-de-Andrade, Helena; Soetens, Loes; Yahaya, Ali Ahmed; Zhang, Wenqing; Vandemaele, Katelijn

2018-01-01

Abstract The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009–2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza – i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden. PMID:29403115

Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science.

PubMed

Siddiqui, Mohammad Shadab; Harrison, Stephen A; Abdelmalek, Manal F; Anstee, Quentin M; Bedossa, Pierre; Castera, Laurent; Dimick-Santos, Lara; Friedman, Scott L; Greene, Katherine; Kleiner, David E; Megnien, Sophie; Neuschwander-Tetri, Brent A; Ratziu, Vlad; Schabel, Elmer; Miller, Veronica; Sanyal, Arun J

2018-05-01

Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001-2012). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

Approaches for assessing health risks from complex mixtures in indoor air: a panel overview.

PubMed Central

Henry, C J; Fishbein, L; Meggs, W J; Ashford, N A; Schulte, P A; Anderson, H; Osborne, J S; Sepkovic, D W

1991-01-01

Critical to a more definitive human health assessment of the potential health risks from exposure to complex mixtures in indoor air is the need for a more definitive clinical measure and etiology of the health effects of complex mixtures. This panel overview highlights six of the eight presentations of the conference panel discussion and features a number of the major topical areas of indoor air concern. W. G. Meggs assessed clinical research priorities with primary focus on the role of volatile organic chemicals in human health, recognizing the areas where definitive data are lacking. By recognizing many types of chemical sensitivity, it may be possible to design studies that can illuminate the mechanisms by which chemical exposure may cause disease. The critically important topic of multiple chemical sensitivity was discussed by N. A. Ashford, who identified four high risk groups and defined the demographics of these groups. P. A. Schulte addressed the issue of biological markers of susceptibility with specific considerations of both methodological and societal aspects that may be operative in the ability to detect innate or inborne differences between individuals and populations. Three case studies were reviewed. H. Anderson discussed the past and present priorities from a public health perspective, focusing on those issues dealing with exposures to environmental tobacco smoke and formaldehyde off-gassing from materials used in mobile home construction. J. J. Osborne described several case studies involving wood smoke exposure to children, with emphasis on the significantly greater occurrence of chronic respiratory symptoms and acute chest illness for children from homes heated with woodburning stoves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1821367

Definition and classification of negative motor signs in childhood.

PubMed

Sanger, Terence D; Chen, Daofen; Delgado, Mauricio R; Gaebler-Spira, Deborah; Hallett, Mark; Mink, Jonathan W

2006-11-01

In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. "Weakness" is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. "Reduced selective motor control" is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. "Ataxia" is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. "Apraxia" is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. "Developmental dyspraxia" is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity.

Aggressive periodontitis: case definition and diagnostic criteria.

PubMed

Albandar, Jasim M

2014-06-01

Aggressive periodontitis is a destructive disease characterized by the following: the involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases. In some patients periodontal tissue loss may commence before puberty, whereas in most patients the age of onset is during or somewhat after the circumpubertal period. Besides infection with specific microorganisms, a host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis, as evidenced by the familial aggregation of the disease. In this article we review the historical background of the diagnostic criteria of aggressive periodontitis, present a contemporary case definition and describe the clinical parameters of the disease. At present, the diagnosis of aggressive periodontitis is achieved using case history, clinical examination and radiographic evaluation. The data gathered using these methods are prone to relatively high measurement errors. Besides, this diagnostic approach measures past disease history and may not reliably measure existing disease activity or accurately predict future tissue loss. A diagnosis is often made years after the onset of the disease, partly because current assessment methods detect established disease more readily and reliably than they detect incipient or initial lesions where the tissue loss is minimal and usually below the detection threshold of present examination methods. Future advancements in understanding the pathogenesis of this disease may contribute to an earlier diagnosis. Insofar, future case definitions may involve the identification of key etiologic and risk factors, combined with high-precision methodologies that enable the early detection of initial lesions. This may significantly enhance the predictive value of these tests and detect cases of aggressive periodontitis before significant tissue loss develops. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interobserver Reliability of the Berlin ARDS Definition and Strategies to Improve the Reliability of ARDS Diagnosis.

PubMed

Sjoding, Michael W; Hofer, Timothy P; Co, Ivan; Courey, Anthony; Cooke, Colin R; Iwashyna, Theodore J

2018-02-01

Failure to reliably diagnose ARDS may be a major driver of negative clinical trials and underrecognition and treatment in clinical practice. We sought to examine the interobserver reliability of the Berlin ARDS definition and examine strategies for improving the reliability of ARDS diagnosis. Two hundred five patients with hypoxic respiratory failure from four ICUs were reviewed independently by three clinicians, who evaluated whether patients had ARDS, the diagnostic confidence of the reviewers, whether patients met individual ARDS criteria, and the time when criteria were met. Interobserver reliability of an ARDS diagnosis was "moderate" (kappa = 0.50; 95% CI, 0.40-0.59). Sixty-seven percent of diagnostic disagreements between clinicians reviewing the same patient was explained by differences in how chest imaging studies were interpreted, with other ARDS criteria contributing less (identification of ARDS risk factor, 15%; cardiac edema/volume overload exclusion, 7%). Combining the independent reviews of three clinicians can increase reliability to "substantial" (kappa = 0.75; 95% CI, 0.68-0.80). When a clinician diagnosed ARDS with "high confidence," all other clinicians agreed with the diagnosis in 72% of reviews. There was close agreement between clinicians about the time when a patient met all ARDS criteria if ARDS developed within the first 48 hours of hospitalization (median difference, 5 hours). The reliability of the Berlin ARDS definition is moderate, driven primarily by differences in chest imaging interpretation. Combining independent reviews by multiple clinicians or improving methods to identify bilateral infiltrates on chest imaging are important strategies for improving the reliability of ARDS diagnosis. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Application of grounded theory to content definition: a case study.

PubMed

Audiss, D; Roth, T

1999-02-01

Successful implementation of a clinical information system requires clinician involvement throughout the process of content definition and system development to ensure acceptance of the automated care process. In these times of downsizing, however, clinicians are not always able to participate fully in the dontent definition phase of system development and often become frustrated with their inability to obtain the patient information they need from the system. The qualitative research principles of grounded theory afford clinicians the opportunity to participate in content definition for information systems. This article presents a case study of the application of grounded theory to develop systematically the content definition for a clinical information system in preparation for implementation on four medical-surgical units.

[18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

PubMed Central

Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

2008-01-01

Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations.

PubMed

Smith, Shannon M; Dart, Richard C; Katz, Nathaniel P; Paillard, Florence; Adams, Edgar H; Comer, Sandra D; Degroot, Aldemar; Edwards, Robert R; Haddox, J David; Jaffe, Jerome H; Jones, Christopher M; Kleber, Herbert D; Kopecky, Ernest A; Markman, John D; Montoya, Ivan D; O'Brien, Charles; Roland, Carl L; Stanton, Marsha; Strain, Eric C; Vorsanger, Gary; Wasan, Ajay D; Weiss, Roger D; Turk, Dennis C; Dworkin, Robert H

2013-11-01

As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment's abuse potential. Copyright © 2013 International Association for the Study of Pain. All rights reserved.

Supraorbital Postmortem Brain Sampling for Definitive Quantitative Confirmation of Cerebral Sequestration of Plasmodium falciparum Parasites

PubMed Central

Milner, Danny A.; Valim, Clarissa; Luo, Robert; Playforth, Krupa B.; Kamiza, Steve; Molyneux, Malcolm E.; Seydel, Karl B.; Taylor, Terrie E.

2012-01-01

Background The conventional clinical case definition of cerebral malaria (CM) is imprecise but specificity is improved by a definitive clinical feature such as retinopathy or confirming sequestration of parasites in a post-mortem examination of the brain. A full autopsy is often not possible, since it is costly and may encounter resistance of the deceased's family. Methods We have assessed the use of a cytological smear of brain tissue, obtained post-mortem by supraorbital sampling, for the purpose of quantifying cerebral sequestration in children with fatal malaria in Blantyre, Malawi. We have compared this method to histological quantification of parasites at autopsy. Results The number of parasites present on cytological smears correlated with the proportion of vessels parasitized as assessed by histology of fixed and stained brain tissue. Use of cytological results in addition to the standard clinical case definition increases the specificity of the clinical case definition alone from 48.3% to 100% with a minimal change in sensitivity. Conclusions Post-mortem supraorbital sampling of brain tissue improves the specificity of the diagnosis of fatal cerebral malaria and provides accurate quantitative estimates of cerebral sequestration. This tool can be of great value in clinical, pathogenetic, and epidemiological research studies on cerebral malaria. PMID:22291197

Applications of multiple-constraint matrix updates to the optimal control of large structures

NASA Technical Reports Server (NTRS)

Smith, S. W.; Walcott, B. L.

1992-01-01

Low-authority control or vibration suppression in large, flexible space structures can be formulated as a linear feedback control problem requiring computation of displacement and velocity feedback gain matrices. To ensure stability in the uncontrolled modes, these gain matrices must be symmetric and positive definite. In this paper, efficient computation of symmetric, positive-definite feedback gain matrices is accomplished through the use of multiple-constraint matrix update techniques originally developed for structural identification applications. Two systems were used to illustrate the application: a simple spring-mass system and a planar truss. From these demonstrations, use of this multiple-constraint technique is seen to provide a straightforward approach for computing the low-authority gains.

47 CFR 76.1200 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Definitions. 76.1200 Section 76.1200... in this subpart: (a) Multichannel video programming system. A distribution system that makes available for purchase, by customers or subscribers, multiple channels of video programming other than an...

40 CFR 437.41 - Special definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... procedures it has adopted will ensure its treatment systems are well-operated and maintained. ... STANDARDS (CONTINUED) THE CENTRALIZED WASTE TREATMENT POINT SOURCE CATEGORY Multiple Wastestreams § 437.41 Special definitions. (a) Initial Certification Statement for this subpart means a written submission to...

40 CFR 437.41 - Special definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... procedures it has adopted will ensure its treatment systems are well-operated and maintained. ... STANDARDS (CONTINUED) THE CENTRALIZED WASTE TREATMENT POINT SOURCE CATEGORY Multiple Wastestreams § 437.41 Special definitions. (a) Initial Certification Statement for this subpart means a written submission to...

40 CFR 437.41 - Special definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... procedures it has adopted will ensure its treatment systems are well-operated and maintained. ... STANDARDS (CONTINUED) THE CENTRALIZED WASTE TREATMENT POINT SOURCE CATEGORY Multiple Wastestreams § 437.41 Special definitions. (a) Initial Certification Statement for this subpart means a written submission to...

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Definitions. 76.800 Section 76.800 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

Detecting borderline infection in an automated monitoring system for healthcare-associated infection using fuzzy logic.

PubMed

de Bruin, Jeroen S; Adlassnig, Klaus-Peter; Blacky, Alexander; Koller, Walter

2016-05-01

Many electronic infection detection systems employ dichotomous classification methods, classifying patient data as pathological or normal with respect to one or several types of infection. An electronic monitoring and surveillance system for healthcare-associated infections (HAIs) known as Moni-ICU is being operated at the intensive care units (ICUs) of the Vienna General Hospital (VGH) in Austria. Instead of classifying patient data as pathological or normal, Moni-ICU introduces a third borderline class. Patient data classified as borderline with respect to an infection-related clinical concept or HAI surveillance definition signify that the data nearly or partly fulfill the definition for the respective concept or HAI, and are therefore neither fully pathological nor fully normal. Using fuzzy sets and propositional fuzzy rules, we calculated how frequently patient data are classified as normal, borderline, or pathological with respect to infection-related clinical concepts and HAI definitions. In dichotomous classification methods, borderline classification results would be confounded by normal. Therefore, we also assessed whether the constructed fuzzy sets and rules employed by Moni-ICU classified patient data too often or too infrequently as borderline instead of normal. Electronic surveillance data were collected from adult patients (aged 18 years or older) at ten ICUs of the VGH. All adult patients admitted to these ICUs over a two-year period were reviewed. In all 5099 patient stays (4120 patients) comprising 49,394 patient days were evaluated. For classification, a part of Moni-ICU's knowledge base comprising fuzzy sets and rules for ten infection-related clinical concepts and four top-level HAI definitions was employed. Fuzzy sets were used for the classification of concepts directly related to patient data; fuzzy rules were employed for the classification of more abstract clinical concepts, and for top-level HAI surveillance definitions. Data for each clinical concept and HAI definition were classified as either normal, borderline, or pathological. For the assessment of fuzzy sets and rules, we compared how often a borderline value for a fuzzy set or rule would result in a borderline value versus a normal value for its associated HAI definition(s). The statistical significance of these comparisons was expressed in p-values calculated with Fisher's exact test. The results showed that, for clinical concepts represented by fuzzy sets, 1-17% of the data were classified as borderline. The number was substantially higher (20-81%) for fuzzy rules representing more abstract clinical concepts. A small body of data were found to be in the borderline range for the four top-level HAI definitions (0.02-2.35%). Seven of ten fuzzy sets and rules were associated significantly more often with borderline values than with normal values for their respective HAI definition(s) (p<0.001). The study showed that Moni-ICU was effective in classifying patient data as borderline for infection-related concepts and top-level HAI surveillance definitions. Copyright © 2016 Elsevier B.V. All rights reserved.

The definition of IVM is clear-variations need defining.

PubMed

De Vos, Michel; Smitz, Johan; Thompson, Jeremy G; Gilchrist, Robert B

2016-11-01

Oocyte in vitro maturation (IVM) is currently defined as the maturation in vitro of immature cumulus-oocyte complexes collected from antral follicles. This is the original definition as first described by Pincus and Enzmann and then by Edwards many decades ago, and this clear and unambiguous definition has served us well ever since. In an attempt to clarify apparent differences among clinicians, the following revised definition of IVM was recently proposed: 'The retrieval of oocytes from small and intermediate sized follicles in an ovary before the largest follicle has surpassed 13 mm in mean diameter'. As such, this proposed definition should encompass the use of hCG triggering. To change the clear and long-serving definition of IVM to fit varying clinical practices requires a compelling justification based on solid scientific and clinical grounds. We are of the opinion that the proposed revised definition of IVM is counterintuitive as it includes protocols that are intended to mature oocytes in vivo The proposed definitions are cumbersome and indeed further complicate the situation. It is not scientifically rational to base the definition on follicular size, and the definition ignores the vast corporate knowledge acquired from the many decades and >6000 publications in animal research that universally practices IVM as per the existing definition. Furthermore, such a definition can lead to false results in interpreting the follow-up of children conceived using IVM. Hence, we see no rationale to change the existing definition of IVM. However, we agree that variations on IVM require alternative nomenclature-these definitions need to be intuitive and need to clearly distinguish themselves from the existing long-standing definition of IVM. This would help to clarify the recent confusion within the clinical ART community as to what is and what is not, IVM. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

International survey among orthopaedic trauma surgeons: Lack of a definition of fracture-related infection.

PubMed

Morgenstern, M; Moriarty, T F; Kuehl, R; Richards, R G; McNally, M A; Verhofstad, M H J; Borens, O; Zalavras, C; Raschke, M; Kates, S L; Metsemakers, W J

2018-03-01

Fracture-related infection (FRI) is one of the most challenging musculoskeletal complications in orthopaedic-trauma surgery. Although the orthopaedic community has developed and adopted a consensus definition of prosthetic joint infections (PJI), it still remains unclear how the trauma surgery community defines FRI in daily clinical practice or in performing clinical research studies. The central aim of this study was to survey the opinions of a global network of trauma surgeons on the definitions and criteria they routinely use, and their opinion on the need for a unified definition of FRI. The secondary aims were to survey their opinion on the utility of currently used definitions that may be at least partially applicable for FRI, and finally their opinion on the important clinical parameters that should be considered as diagnostic criteria for FRI. An 11-item questionnaire was developed to cover the above-mentioned aims. The questionnaire was administered by SurveyMonkey and was sent via blast email to all registered users of AO Trauma (Davos, Switzerland). Out of the 26'563 recipients who opened the email, 2'327 (8.8%) completed the questionnaire. Nearly 90% of respondents agreed that a consensus-derived definition for FRI is required and 66% of the surgeons also agreed that PJI and FRI are not equal with respect to diagnosis, treatment and outcome. Furthermore, "positive cultures from microbiology testing", "elevation of CRP", "purulent drainage" and "local clinical signs of infection" were voted the most important diagnostic parameters for FRI. This international survey infers the need for a consensus definition of FRI and provides insight into the clinical parameters seen by an international community of trauma surgeons as being critical for defining FRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intravascular migration of a broken cerclage wire into the left heart.

PubMed

Leonardi, Francesco; Rivera, Fabrizio

2014-10-01

This article describes a patient in whom a broken cerclage wire migrated from the left hip into the left ventricle. A 71-year-old woman was admitted to the authors' hospital for preoperative examination before femoral hernia repair. Chest radiograph showed a metallic wire in the left ventricle. Twenty-four years earlier, she had a revision arthroplasty. During revision surgery, fragments of the osteotomy were fixed to the femur with multiple cerclage wires. During the past 5 years, radiographic follow-up showed progressive multiple ruptures of cerclage wires. The cerclage wiring was not removed because the patient had no related clinical symptoms. Radiograph of the left hip showed a well-fixed cemented acetabular ring and an uncemented femoral stem with a healed trochanteric osteotomy. All cerclage wires were broken into multiple parts, and it was very difficult to determine which part had migrated into the heart. Thoracic computed tomography scan showed wire that had migrated into the anterior left ventricular myocardial wall at the atrioventricular level. The patient had no clinical symptoms. Electrocardiogram showed a normal sinus rhythm and right bundle branch block. Because of the high risk of surgical left ventriculotomy associated with searching for wire that had migrated into the myocardial wall, patient monitoring was planned. Definitive management of this complication constitutes a dilemma. Although this complication is highly unusual, the possibility of intracardiac migration of broken wire should be considered when deciding on prophylactic surgical removal of hardware after fracture or osteotomy healing. Copyright 2014, SLACK Incorporated.

Defining and assessing wisdom: a review of the literature.

PubMed

Bangen, Katherine J; Meeks, Thomas W; Jeste, Dilip V

2013-12-01

With increasing longevity and a growing focus on successful aging, there has been a recent growth of research designed to operationalize and assess wisdom. We aimed to (1) investigate the degree of overlap among empirical definitions of wisdom, (2) identify the most commonly cited wisdom subcomponents, (3) examine the psychometric properties of existing assessment instruments, and (4) investigate whether certain assessment procedures work particularly well in tapping the essence of subcomponents of the various empirical definitions. We searched PsychINFO-indexed articles published through May 2012 and their bibliographies. Studies were included if they were published in a peer-reviewed journal and (1) proposed a definition of wisdom or (2) discussed the development or validation of an instrument designed to assess wisdom. Thirty-one articles met inclusion criteria. Despite variability among the 24 reviewed definitions, there was significant overlap. Commonly cited subcomponents of wisdom included knowledge of life, prosocial values, self-understanding, acknowledgment of uncertainty, emotional homeostasis, tolerance, openness, spirituality, and sense of humor. Published reports describing the psychometric properties of nine instruments varied in comprehensiveness but most measures were examined for selected types of reliability and validity, which were generally acceptable. Given limitations of self-report procedures, an approach integrating multiple indices (e.g., self-report and performance-based measures) may better capture wisdom. Significant progress in the empirical study of wisdom has occurred over the past four decades; however, much needs to be done. Future studies with larger, more diverse samples are needed to determine the generalizability, usefulness, and clinical applicability of these definitions and assessment instruments. Such work will have relevance for the fields of geriatrics, psychiatry, psychology, sociology, education, and public health, among others. Copyright © 2013 American Association for Geriatric Psychiatry. All rights reserved.

State-of-the-Art: Hypo-responsiveness to oral antiplatelet therapy in patients with type 2 diabetes mellitus.

PubMed

Kumbhani, Dharam J; Marso, Steven P; Alvarez, Carlos A; McGuire, Darren K

2015-01-01

Diabetes mellitus is a global pandemic, associated with a high burden of cardiovascular disease. There are multiple platelet derangements in patients with diabetes, and antiplatelet drugs remain the first-line agents for secondary prevention as well as for high-risk primary prevention among patients with diabetes. This review provides a summary of oral antiplatelet drug hypo-responsiveness in patients with diabetes, specifically aspirin and Clopidogrel resistance. Topics discussed include antiplatelet testing, definitions used to define hypo-response and resistance, its prevalence, association with clinical outcomes and strategies to mitigate resistance. The role of prasugrel and ticagrelor, as well as investigational agents, is also discussed.

CT arthrographic patterns in recurrent glenohumeral instability.

PubMed

Singson, R D; Feldman, F; Bigliani, L

1987-10-01

CT double-contrast arthrograms were performed on 54 shoulders in 53 patients with recurrent dislocation or subluxation to detect responsible underlying bony or soft-tissue abnormalities. Lesions of the anterior labrum in 52 (96%) of 54 cases and of the capsuloligamentous complex in 42 (78%) of 54 cases were the two most common abnormalities. There was no difference in the degree or number of labral lesions between subluxations and dislocations. However, more severe capsular lesions, subscapularis tendon tears, and widened subscapularis bursae were consistently found among patients with dislocations. Subsequent clinical, arthroscopic, and surgical findings showed that the use of CT double-contrast arthrograms resulted in improved definition of the multiple lesions associated with glenohumeral dysfunction.

[Epilepsy, vertigo, dizziness, headache, emesis as neurological manifestation in a Giteleman's Sindrome case].

PubMed

Delsere, Mirco; Campogiani, Vincenzo; Carletti, Vincenzo; Mancini, Stefania; Piccinini, Nadia; Castelli, Paolo; Sopranzi, Franco

2015-01-01

We report the case of a woman presenting the recent onset of multiple seizure and epilepsy episodes combined with other neurological symptoms (e.g. vertigo, dizziness, vomiting, headache). She was resistant to antiepileptic and symptomatic therapy, having been first admitted to the neurology ward and subsequently to the general medicine ward. In this case, several patient assessments and imaging exams were not conclusive evidence of specific etiopathogenesis, or definitive neurological illness; however, the patient showed laboratory indexes compatible with Gitelmans Syndrome. The correction of the electrolytic imbalances of tubulopathy (including low magnesium and potassium levels) led to the progressive improvement of clinical manifestations and the eventual interruption of the antiepileptic therapy.

[A retrospective clinicopathological study of aspiration pneumonia in the elderly].

PubMed

Pu, Chun; Zhong, Xuefeng; Fang, Fang; Yang, Yimeng; Xu, Xiaomao; Sun, Tieying

2014-08-01

To explore the clinicopathological characteristics of aspiration pneumonia in the elderly. The clinical data of 30 cases of autopsy-proven aspiration pneumonia in Beijing Hospital from 1973 to 2002 were reviewed. The patients consisted of 28 males and 2 females, aged from 63 to 103 [mean (83 ± 9)] years. Only 15 cases were clinically diagnosed as aspiration pneumonia before death. Concomitant diseases were severe and complex, mostly coronary disease, cerebrovascular disease, hypertension, COPD, and diabetes mellitus. All the patients suffered from at least 3 concomitant diseases. Long-term bedridden and nasogastric feeding was seen in 11 and 17 patients respectively. The clinical presentation and chest X-ray of aspiration pneumonia in the elderly were nonspecific and variable. Mixed infections were common . The main bacteria isolated were Gram-negative bacilli, in particular Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli and Candida albicans. By pathology, macrophages with foreign bodies were found in all the 30 cases and multiple small abscesses were found in 14 cases. The lesions were adjacent to the bronchioles and in the lung tissue around the bronchioles, mostly multi-lobar and bilateral. Unilateral or bilateral pleural effusion developed in 20 patients. The accordance between radiological and pathological diagnosis of aspiration pneumonia was very poor. The foci of infection detected by X-ray were proven by autopsy in 13 patients, while pleural effusions in X-ray were proven by autopsy in 15 patients. Multi-concomitant diseases, mixed infection and extra-pulmonary presentations were common in elderly patients with aspiration pneumonia. Multiple small abscesses were the pathological characteristics of aspiration pneumonia in the aged. A definite clinical diagnosis of aspiration pneumonia was difficult. Recurrent silent microaspiration was a feature of aspiration in the elderly. The assessment of risk factor of aspiration played an important role in the clinical diagnosis of aspiration pneumonia.

Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study

PubMed Central

Leray, Emmanuelle; Vukusic, Sandra; Debouverie, Marc; Clanet, Michel; Brochet, Bruno; de Sèze, Jérôme; Zéphir, Hélène; Defer, Gilles; Lebrun-Frenay, Christine; Moreau, Thibault; Clavelou, Pierre; Pelletier, Jean; Berger, Eric; Cabre, Philippe; Camdessanché, Jean-Philippe; Kalson-Ray, Shoshannah; Confavreux, Christian; Edan, Gilles

2015-01-01

Background Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France. Objectives Estimate survival in MS patients and compare mortality with that of the French general population. Methods We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration. Results After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]). Conclusions This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression. PMID:26148099

Review of the operational definition for first-episode psychosiseip

PubMed Central

Breitborde, Nicholas J. K.; Srihari, Vinod H.; Woods, Scott W.

2015-01-01

Aim Given the growing interest in the study of first-episode psychosis, clinical and research programmes would benefit from a conceptual clarification of how to operationalize ‘first-episode psychosis’. We review the variety of definitions in use and discuss their relative merits with respect to both clinical (e.g. early treatment) and research (e.g. obtaining meaningfully homogeneous populations) agendas. Methods We completed a selective review of the literature to investigate how first-episode psychosis was operationally defined. Results Operational definitions for ‘first-episode psychosis’ fall largely into three categories: (i) first treatment contact; (ii) duration of antipsychotic medication use; and (iii) duration of psychosis. Each definitional category contains a number of underlying assumptions that contribute to the strengths and weaknesses of the definition. Conclusions The term ‘first-episode psychosis’ as used within clinical and research settings is misleading regardless of which operational definition is used. This term is typically used to refer to individuals early in the course of a psychotic illness or treatment rather than individuals who are truly in the midst of a first ‘episode’ of illness. The alternative of ‘recent-onset psychosis’ with related definitions based on ‘duration of psychosis’ is proposed. Based on this review, we provide suggestions with regard to the overarching pragmatic consideration of setting up a clinical service that can attract and assemble a population of early psychosis patients for the related purposes of treatment and research. PMID:22642728

Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group.

PubMed

Rodeghiero, Francesco; Stasi, Roberto; Gernsheimer, Terry; Michel, Marc; Provan, Drew; Arnold, Donald M; Bussel, James B; Cines, Douglas B; Chong, Beng H; Cooper, Nichola; Godeau, Bertrand; Lechner, Klaus; Mazzucconi, Maria Gabriella; McMillan, Robert; Sanz, Miguel A; Imbach, Paul; Blanchette, Victor; Kühne, Thomas; Ruggeri, Marco; George, James N

2009-03-12

Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.

Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis.

PubMed

Buchinsky, Farrel J; Donfack, Joseph; Derkay, Craig S; Choi, Sukgi S; Conley, Stephen F; Myer, Charles M; McClay, John E; Campisi, Paolo; Wiatrak, Brian J; Sobol, Steven E; Schweinfurth, John M; Tsuji, Domingos H; Hu, Fen Z; Rockette, Howard E; Ehrlich, Garth D; Post, J Christopher

2008-05-28

RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Time to definitive diagnosis of breast cancer in Latina and non-Hispanic white women: the six cities study.

PubMed

Ramirez, Amelie G; Pérez-Stable, Eliseo J; Talavera, Gregory A; Penedo, Frank J; Carrillo, J Emilio; Fernandez, Maria E; Muñoz, Edgar; Long Parma, Dorothy; Holden, Alan Ec; San Miguel de Majors, Sandra; Nápoles, Anna; Castañeda, Sheila F; Gallion, Kipling J

2013-12-01

Time delay after an abnormal screening mammogram may have a critical impact on tumor size, stage at diagnosis, treatment, prognosis, and survival of subsequent breast cancer. This study was undertaken to evaluate disparities between Latina and non-Hispanic white (NHW) women in time to definitive diagnosis of breast cancer after an abnormal screening mammogram, as well as factors contributing to such disparities. As part of the activities of the National Cancer Institute (NCI)-funded Redes En Acción research network, clinical records of 186 Latinas and 74 NHWs who received abnormal screening mammogram results were reviewed to determine the time to obtain a definitive diagnosis. Data was obtained from participating clinics in six U.S. cities and included demographics, clinical history, and mammogram characteristics. Kaplan-Meier estimates and Cox proportional hazards models were used to test differences in median time to definitive diagnosis by ethnicity after adjusting for clinic site, demographics, and clinical characteristics. Time-to-event analysis showed that Latinas took 2.2 times longer to reach 50% definitively diagnosed with breast cancer relative to NHWs, and three times longer to reach 80% diagnosed (p=0.001). Latinas' median time to definitive diagnosis was 60 days compared to 27 for NHWs, a 59% gap in diagnosis rates (adjusted Hazard Ratio [aHR] = 1.59, 95% CI = 1.09, 2.31; p=0.015). BI-RADS-4/5 women's diagnosis rate was more than twice that of BI-RADS-3 (aHR = 2.11, 95% CI = 1.18, 3.78; p=0.011). Disparities in time between receipt of abnormal screening result and definitive diagnosis adversely affect Latinas compared to NHWs, and remain significant after adjusting for demographic and clinical variables. With cancer now the leading cause of mortality among Latinos, a greater need exists for ethnically and culturally appropriate interventions like patient navigation to facilitate Latinas' successful entry into, and progression through, the cancer care system.

Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

PubMed

Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

2015-11-01

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

What is the definition of sports-related concussion: a systematic review.

PubMed

McCrory, Paul; Feddermann-Demont, Nina; Dvořák, Jiří; Cassidy, J David; McIntosh, Andrew; Vos, Pieter E; Echemendia, Ruben J; Meeuwisse, Willem; Tarnutzer, Alexander A

2017-06-01

Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC. This is a systematic literature review. Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016). Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data. Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation. SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A survey of Australian prosthodontists: The use of posts in endodontically treated teeth.

PubMed

Sambrook, Raelene; Burrow, Michael

2018-05-09

This study aimed to gain insight into common practices of Australian prosthodontists when placing a post in an endodontically treated tooth (ETT). A 17-question open- and closed- format questionnaire was sent to registered Australian prosthodontists. The response rate was 55% (n=95). The majority of respondents indicated the purpose of a post was to retain a core (n=94, 99%). The decision to place a post is affected by the quantity of remaining tooth structure (n=91, 96%) and the definitive restoration (n=68, 72%). The ideal post length is neither a short nor long post with the most frequent response (n=52, 34%) being 'as long as possible without disturbing the apical seal'. The apical seal requirements were defined as 4-5mm of Gutta Percha for 77% of respondents. The most preferred post type was a custom cast metal post (n=85, 49%). The most popular luting cement was resin composite (n=84, 39%). The results from this survey do not provide a definitive guide for restoring an ETT. However, it illustrates how Australian prosthodontists address this clinical challenge. The multiple responses received for a number of questions suggest that the material and technique employed in the Australian context is influenced by the individual clinical case. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Basic mechanisms of urgency: preclinical and clinical evidence.

PubMed

Michel, Martin C; Chapple, Christopher R

2009-08-01

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

Patients' misunderstanding of common orthopaedic terminology: the need for clarity

PubMed Central

Bagley, CHM; Hunter, AR; Bacarese-Hamilton, IA

2011-01-01

INTRODUCTION Patients' understanding of their medical problems is essential to allow them to make competent decisions, comply with treatment and enable recovery. We investigated Patients' understanding of orthopaedic terms to identify those words surgeons should make the most effort to explain. METHODS This questionnaire-based study recruited patients attending the orthopaedic clinics. Qualitative and quantitative data were collected using free text boxes for the Patients' written definitions and multiple choice questions (MCQs). RESULTS A total of 133 patients took part. Of these, 74% identified English as their first language. ‘Broken bone’ was correctly defined by 71% of respondents whereas ‘fractured bone’ was only correctly defined by 33%. ‘Sprain’ was correctly defined by 17% of respondents, with 29% being almost correct, 25% wrong and 29% unsure. In the MCQs, 51% of respondents answered correctly for ‘fracture’, 55% for ‘arthroscopy’, 46% for ‘meniscus’, 35% for ‘tendon’ and 23% for ‘ligament’. ‘Sprained’ caused confusion, with only 11% of patients answering correctly. Speaking English as a second language was a significant predictive factor for patients who had difficulty with definitions. There was no significant variation among different age groups. CONCLUSIONS Care should be taken by surgeons when using basic and common orthopaedic terminology in order to avoid misunderstanding. Educating patients in clinic is a routine part of practice. PMID:21943466

Simulating pad-electrodes with high-definition arrays in transcranial electric stimulation

NASA Astrophysics Data System (ADS)

Kempe, René; Huang, Yu; Parra, Lucas C.

2014-04-01

Objective. Research studies on transcranial electric stimulation, including direct current, often use a computational model to provide guidance on the placing of sponge-electrode pads. However, the expertise and computational resources needed for finite element modeling (FEM) make modeling impractical in a clinical setting. Our objective is to make the exploration of different electrode configurations accessible to practitioners. We provide an efficient tool to estimate current distributions for arbitrary pad configurations while obviating the need for complex simulation software. Approach. To efficiently estimate current distributions for arbitrary pad configurations we propose to simulate pads with an array of high-definition (HD) electrodes and use an efficient linear superposition to then quickly evaluate different electrode configurations. Main results. Numerical results on ten different pad configurations on a normal individual show that electric field intensity simulated with the sampled array deviates from the solutions with pads by only 5% and the locations of peak magnitude fields have a 94% overlap when using a dense array of 336 electrodes. Significance. Computationally intensive FEM modeling of the HD array needs to be performed only once, perhaps on a set of standard heads that can be made available to multiple users. The present results confirm that by using these models one can now quickly and accurately explore and select pad-electrode montages to match a particular clinical need.

IT Infrastructure Components for Biobanking

PubMed Central

Prokosch, H.U.; Beck, A.; Ganslandt, T.; Hummel, M.; Kiehntopf, M.; Sax, U.; Ückert, F.; Semler, S.

2010-01-01

Objective Within translational research projects in the recent years large biobanks have been established, mostly supported by homegrown, proprietary software solutions. No general requirements for biobanking IT infrastructures have been published yet. This paper presents an exemplary biobanking IT architecture, a requirements specification for a biorepository management tool and exemplary illustrations of three major types of requirements. Methods We have pursued a comprehensive literature review for biobanking IT solutions and established an interdisciplinary expert panel for creating the requirements specification. The exemplary illustrations were derived from a requirements analysis within two university hospitals. Results The requirements specification comprises a catalog with more than 130 detailed requirements grouped into 3 major categories and 20 subcategories. Special attention is given to multitenancy capabilities in order to support the project-specific definition of varying research and bio-banking contexts, the definition of workflows to track sample processing, sample transportation and sample storage and the automated integration of preanalytic handling and storage robots. Conclusion IT support for biobanking projects can be based on a federated architectural framework comprising primary data sources for clinical annotations, a pseudonymization service, a clinical data warehouse with a flexible and user-friendly query interface and a biorepository management system. Flexibility and scalability of all such components are vital since large medical facilities such as university hospitals will have to support biobanking for varying monocentric and multicentric research scenarios and multiple medical clients. PMID:23616851

Older kidneys donor transplantation: five years' experience without biopsy and using clinical laboratory and macroscopic anatomy evaluation.

PubMed

Santangelo, M; Zuccaro, M; De Rosa, P; Tammaro, V; Grassia, S; Federico, S; Ciotola, A L; Spinosa, G; Renda, A

2007-01-01

The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy. Between 2000 and 2005, 58 older kidneys were harvested: 27 were transplanted in our center; 13 were discarded; and 18 were transplanted in other centers. We considered 3 factors to define kidney quality: macroscopic anatomy, multiple factors linked to the donor, and clinical-laboratory data. After transplantation, we observed the patients for at least 1 year and up to 6 years. At 1 year, 24/27 (89%) patients had a functional kidney, 2 patients showed an initial renal failure and 1 patient lost the kidney. At maximum follow-up, 19 patients (70%) had functional kidneys, 4 with initial renal failure. These results compared with the kidneys harvested using Standard Donor Kidney Criteria are acceptable. Obviously we need long-term follow-up to increase, the amount of data and obtain a definitive outcome. Biopsy is the gold standard for the definition of an older kidney's quality. When a biopsy is not feasible, the study of the macroscopic anatomy the kidney's donor and of some donor's parameters represent an acceptable biopsy alternative, being able to rescue some organs that would be otherwise lost.

IT Infrastructure Components for Biobanking.

PubMed

Prokosch, H U; Beck, A; Ganslandt, T; Hummel, M; Kiehntopf, M; Sax, U; Uckert, F; Semler, S

2010-01-01

Within translational research projects in the recent years large biobanks have been established, mostly supported by homegrown, proprietary software solutions. No general requirements for biobanking IT infrastructures have been published yet. This paper presents an exemplary biobanking IT architecture, a requirements specification for a biorepository management tool and exemplary illustrations of three major types of requirements. We have pursued a comprehensive literature review for biobanking IT solutions and established an interdisciplinary expert panel for creating the requirements specification. The exemplary illustrations were derived from a requirements analysis within two university hospitals. The requirements specification comprises a catalog with more than 130 detailed requirements grouped into 3 major categories and 20 subcategories. Special attention is given to multitenancy capabilities in order to support the project-specific definition of varying research and bio-banking contexts, the definition of workflows to track sample processing, sample transportation and sample storage and the automated integration of preanalytic handling and storage robots. IT support for biobanking projects can be based on a federated architectural framework comprising primary data sources for clinical annotations, a pseudonymization service, a clinical data warehouse with a flexible and user-friendly query interface and a biorepository management system. Flexibility and scalability of all such components are vital since large medical facilities such as university hospitals will have to support biobanking for varying monocentric and multicentric research scenarios and multiple medical clients.

40 CFR 437.41 - Special definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... are well-operated and maintained; and (5) Explain why the procedures it has adopted will ensure its... STANDARDS THE CENTRALIZED WASTE TREATMENT POINT SOURCE CATEGORY Multiple Wastestreams § 437.41 Special definitions. (a) Initial Certification Statement for this subpart means a written submission to the...

40 CFR 437.41 - Special definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... are well-operated and maintained; and (5) Explain why the procedures it has adopted will ensure its... STANDARDS THE CENTRALIZED WASTE TREATMENT POINT SOURCE CATEGORY Multiple Wastestreams § 437.41 Special definitions. (a) Initial Certification Statement for this subpart means a written submission to the...

Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. AUSTIMS Research Group.

PubMed Central

1989-01-01

The role of interferon-alpha (IFN-alpha) and transfer factor (TF) in the treatment of multiple sclerosis was investigated in a prospective, multi-centric, three year, double-blind, placebo-controlled trial. One hundred and eighty two patients with clinically definite multiple sclerosis were randomised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status. Subcutaneous injections of IFN-alpha (3 x 10(6) units), TF (0.5 units) manufactured from leucocytes of cohabiting donors, or placebo were given twice weekly for two months, once weekly for 10 months then fortnightly for 24 months. One hundred and fifty three patients completed the injection regimen. There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group. Similarly, change in visual evoked responses (VER), and in number of oligoclonal bands (OCB) and the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) over the trial period did not differ significantly between the three groups. However, the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups. PMID:2659737

SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions.

PubMed

Beneteau, Claire; Cavé, Hélène; Moncla, Anne; Dorison, Nathalie; Munnich, Arnold; Verloes, Alain; Leheup, Bruno

2009-10-01

We report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of Noonan syndrome. Two patients show mutations in PTPN11 (p.Tyr62Asp and p.Asn308Asp) and three in SOS1 (p.Arg552Ser and p.Arg552Thr). The latter are the first SOS1 mutations reported outside PTPN11 in NL/MGCL syndrome. MGCL lesions were observed in jaws ('cherubism') and joints ('pigmented villonodular synovitis'). We show through those patients that both types of MGCL are not PTPN11-specific, but rather represent a low penetrant (or perhaps overlooked) complication of the dysregulated RAS/MAPK signaling pathway. We recommend discarding NL/MGCL syndrome from the nosology, as this presentation is neither gene-nor allele-specific of Noonan syndrome; these patients should be described as Noonan syndrome with MGCL (of the mandible, the long bone...). The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

The International Glossary on Infertility and Fertility Care, 2017†‡§

PubMed Central

Zegers-Hochschild, Fernando; Adamson, G David; Dyer, Silke; Racowsky, Catherine; de Mouzon, Jacques; Sokol, Rebecca; Rienzi, Laura; Sunde, Arne; Schmidt, Lone; Cooke, Ian D; Simpson, Joe Leigh; van der Poel, Sheryl

2017-01-01

Abstract STUDY QUESTION Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? SUMMARY ANSWER A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, DURATION Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, METHODS Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN RESULTS AND THE ROLE OF CHANCE A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as ‘fertility care’ and ‘fertility awareness’ together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of ‘infertility’ has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, REASONS FOR CAUTION All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. WIDER IMPLICATIONS OF THE FINDINGS Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS None. TRIAL REGISTRATION NUMBER N/A. PMID:29117321

Defining delirium for the International Classification of Diseases, 11th Revision.

PubMed

Meagher, David J; Maclullich, Alasdair M J; Laurila, Jouko V

2008-09-01

The development of ICD-11 provides an opportunity to update the description of delirium according to emerging data that have added to our understanding of this complex neuropsychiatric syndrome. Synthetic article based on published work considered by the authors to be relevant to the definition of delirium. The current DSM-IV definition of delirium is preferred to the ICD-10 because of its greater inclusivity. Evidence does not support major changes in the principal components of present definitions but a number of key issues for the updated definition were identified. These include better account of non-cognitive features, more guidance for rating contextual diagnostic items, clearer definition regarding the interface with dementia, and accounting for illness severity, clinical subtypes and course. Development of the ICD definition of delirium can allow for more targeted research and clinical effort.

A Framework to Support the Sharing and Reuse of Computable Phenotype Definitions Across Health Care Delivery and Clinical Research Applications.

PubMed

Richesson, Rachel L; Smerek, Michelle M; Blake Cameron, C

2016-01-01

The ability to reproducibly identify clinically equivalent patient populations is critical to the vision of learning health care systems that implement and evaluate evidence-based treatments. The use of common or semantically equivalent phenotype definitions across research and health care use cases will support this aim. Currently, there is no single consolidated repository for computable phenotype definitions, making it difficult to find all definitions that already exist, and also hindering the sharing of definitions between user groups. Drawing from our experience in an academic medical center that supports a number of multisite research projects and quality improvement studies, we articulate a framework that will support the sharing of phenotype definitions across research and health care use cases, and highlight gaps and areas that need attention and collaborative solutions. An infrastructure for re-using computable phenotype definitions and sharing experience across health care delivery and clinical research applications includes: access to a collection of existing phenotype definitions, information to evaluate their appropriateness for particular applications, a knowledge base of implementation guidance, supporting tools that are user-friendly and intuitive, and a willingness to use them. We encourage prospective researchers and health administrators to re-use existing EHR-based condition definitions where appropriate and share their results with others to support a national culture of learning health care. There are a number of federally funded resources to support these activities, and research sponsors should encourage their use.

A Framework to Support the Sharing and Reuse of Computable Phenotype Definitions Across Health Care Delivery and Clinical Research Applications

PubMed Central

Richesson, Rachel L.; Smerek, Michelle M.; Blake Cameron, C.

2016-01-01

Introduction: The ability to reproducibly identify clinically equivalent patient populations is critical to the vision of learning health care systems that implement and evaluate evidence-based treatments. The use of common or semantically equivalent phenotype definitions across research and health care use cases will support this aim. Currently, there is no single consolidated repository for computable phenotype definitions, making it difficult to find all definitions that already exist, and also hindering the sharing of definitions between user groups. Method: Drawing from our experience in an academic medical center that supports a number of multisite research projects and quality improvement studies, we articulate a framework that will support the sharing of phenotype definitions across research and health care use cases, and highlight gaps and areas that need attention and collaborative solutions. Framework: An infrastructure for re-using computable phenotype definitions and sharing experience across health care delivery and clinical research applications includes: access to a collection of existing phenotype definitions, information to evaluate their appropriateness for particular applications, a knowledge base of implementation guidance, supporting tools that are user-friendly and intuitive, and a willingness to use them. Next Steps: We encourage prospective researchers and health administrators to re-use existing EHR-based condition definitions where appropriate and share their results with others to support a national culture of learning health care. There are a number of federally funded resources to support these activities, and research sponsors should encourage their use. PMID:27563686

Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

PubMed

Lublin, Fred D; Cofield, Stacey S; Cutter, Gary R; Conwit, Robin; Narayana, Ponnada A; Nelson, Flavia; Salter, Amber R; Gustafson, Tarah; Wolinsky, Jerry S

2013-03-01

A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. Copyright © 2013 American Neurological Association.

What is "grazing"? Reviewing its definition, frequency, clinical characteristics, and impact on bariatric surgery outcomes, and proposing a standardized definition.

PubMed

Conceição, Eva M; Mitchell, James E; Engel, Scott G; Machado, Paulo P P; Lancaster, Kathryn; Wonderlich, Stephen A

2014-01-01

Grazing, characterized by a repetitive eating pattern, has received increased attention among bariatric surgery patients. However, different definitions and terminology have been used, preventing the accurate measurement of this phenomenon and comparison of data across studies. To review existing definitions and associated clinical features of grazing among different samples and to propose a standardized definition that will allow for consistency in future work. University and Clinical Research Institute. Of the 39 studies found, 9 provided an original definition and 12 provided data of its association with weight outcomes. Six were studies of nonbariatric surgery populations. Based on this literature review, the most common criteria used in previous studies to define grazing were included in a survey that was sent to 24 individuals who have published work in the field. These experts were asked to provide their opinion on what should constitute grazing. Grazing is a frequent behavior in the bariatric surgery population as well as in eating disordered and community samples. Its association with psychopathology is not clear, but its negative impact on weight outcomes after bariatric surgery generally has been supported. Survey data provided a consensus regarding the definition of grazing as an eating behavior characterized by the repetitive eating (more than twice) of small/modest amounts of food in an unplanned manner, with what we characterize as compulsive and noncompulsive subtypes. Given the clinical relevance of grazing among bariatric surgery patients, a unique definition is crucial to better study its associated features and impact on different populations. Copyright © 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Clinical Criteria Versus a Possible Research Case Definition in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

PubMed

Jason, Leonard A; McManimen, Stephanie; Sunnquist, Madison; Newton, Julia L; Strand, Elin Bolle

2017-01-01

The Institute of Medicine (IOM) recently developed clinical criteria for what had been known as chronic fatigue syndrome (CFS). Given the broad nature of the clinical IOM criteria, there is a need for a research definition that would select a more homogenous and impaired group of patients than the IOM clinical criteria. At the present time, it is unclear what will serve as the research definition. The current study focused on a research definition which selected homebound individuals who met the four IOM criteria, excluding medical and psychiatric co-morbidities. Our research criteria were compared to those participants meeting the IOM criteria. Those not meeting either of these criteria sets were placed in a separate group defined by 6 or more months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and the SF-36. Due to unequal sample sizes and variances, Welch's F tests and Games-Howell post hoc tests were conducted. Using a large database of over 1,000 patients from several countries, we found that those meeting a more restrictive research definition were even more impaired and more symptomatic than those meeting criteria for the other two groups. Deciding on a particular research case definition would allow researchers to select more comparable patient samples across settings, and this would represent one of the most significant methodologic advances for this field of study.

Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood.

PubMed

Kuerten, Stefanie; Pommerschein, Giovanna; Barth, Stefanie K; Hohmann, Christopher; Milles, Bianca; Sammer, Fabian W; Duffy, Cathrina E; Wunsch, Marie; Rovituso, Damiano M; Schroeter, Michael; Addicks, Klaus; Kaiser, Claudia C; Lehmann, Paul V

2014-01-01

B cells are increasingly coming into play in the pathogenesis of multiple sclerosis (MS). Here, we screened peripheral blood mononuclear cells (PBMC) from patients with clinically isolated syndrome (CIS), MS, other non-inflammatory neurological, inflammatory neurological or autoimmune diseases, and healthy donors for their B cell reactivity to CNS antigen using the enzyme-linked immunospot technique (ELISPOT) after 96 h of polyclonal stimulation. Our data show that nine of 15 patients with CIS (60.0%) and 53 of 67 patients with definite MS (79.1%) displayed CNS-reactive B cells, compared to none of the control donors. The presence of CNS-reactive B cells in the blood of the majority of patients with MS or at risk to develop MS along with their absence in control subjects suggests that they might be indicative of a B cell-dependent subpopulation of the disease. Copyright © 2014. Published by Elsevier Inc.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

PubMed Central

IV, Edward C Oldfield; III, Edward C Oldfield; Johnson, David A

2014-01-01

Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies. PMID:24729930

Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients.

PubMed

Harder, Anja; Wesemann, Martin; Hagel, Christian; Schittenhelm, Jens; Fischer, Susan; Tatagiba, Marcos; Nagel, Christoph; Jeibmann, Astrid; Bohring, Axel; Mautner, Victor-Felix; Paulus, Werner

2012-05-01

We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses.

Thromboelastographic evidence of inhibition of fibrinolysis after ε-aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy.

PubMed

Yoo, Seung H; Venn, Emilee; Sullivan, Lauren A; Olver, Christine S

2016-09-01

To describe the thromboelastographic changes in fibrinolysis with ε-aminocaproic acid treatment in a dog with suspected acute traumatic coagulopathy. A 9-year-old female spayed Airedale Terrier was presented with multiple injuries consistent with motor vehicle trauma. After surgical repair of a diaphragmatic hernia and minor laceration of the right cranial lung lobe, the dog continued to produce copious volumes of hemorrhagic fluid from the thoracic cavity despite multiple plasma transfusions, autotransfusions, and failure to locate a definitive source of bleeding during 2 separate surgeries. ε-Aminocaproic acid treatment was initiated and was associated with rapid clinical improvement and diminished fibrinolysis based on a modified plasma-based thromboelastogram. This report describes thromboelastographic evidence of inhibition of fibrinolysis after ε-aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy. Thromboelastrography may be useful in monitoring therapy with antifibrinolytic drugs. © Veterinary Emergency and Critical Care Society 2016.

Pelvic pain: a pathway for care developed for both men and women by the British Pain Society.

PubMed

Baranowski, A P; Lee, J; Price, C; Hughes, J

2014-03-01

This paper aims to explain the key points and highlight some of the controversies in the development of the British Pain Society's pelvic pain patient pathway map. Many clinicians lack experience and confidence with this group of patients, and this issue is highlighted. Additionally, the difficulties of classification and definitions in this area are discussed in detail. These are historical causes of disagreement among specialists which can lead to confused clinical care. This group of patients have multiple issues that cross many professional boundaries; they are best managed by the co-ordinated involvement of multiple teams. Patients suffer from significant distress and disability that often needs specialist assessment and intervention (interdisciplinary). This suggests that an integrated approach is required across the historic boundaries of primary and secondary care. A variety of interventions, including opioids and neuromodulation are recommended in the pathway and the controversies surrounding these inclusions are aired in detail.

3D Fast Spin Echo T2-weighted Contrast for Imaging the Female Cervix

NASA Astrophysics Data System (ADS)

Vargas Sanchez, Andrea Fernanda

Magnetic Resonance Imaging (MRI) with T2-weighted contrast is the preferred modality for treatment planning and monitoring of cervical cancer. Current clinical protocols image the volume of interest multiple times with two dimensional (2D) T2-weighted MRI techniques. It is of interest to replace these multiple 2D acquisitions with a single three dimensional (3D) MRI acquisition to save time. However, at present the image contrast of standard 3D MRI does not distinguish cervical healthy tissue from cancerous tissue. The purpose of this thesis is to better understand the underlying factors that govern the contrast of 3D MRI and exploit this understanding via sequence modifications to improve the contrast. Numerical simulations are developed to predict observed contrast alterations and to propose an improvement. Improvements of image contrast are shown in simulation and with healthy volunteers. Reported results are only preliminary but a promising start to establish definitively 3D MRI for cervical cancer applications.

[Status and progress of stimulating parameters in acupuncture treatment of ischemic cerebrovascular disease].

PubMed

Wei, Yuan-yuan; Fan, Xiao-nong; Wang, Shu; Shi, Xue-min

2008-08-01

Acute ischemic cerebrovascular disease is one of the critical diseases seriously endangering human health. Acupuncture therapy, an effective treatment method for many types of disorders has been generally acknowledged. In recent years, many scientific researchers have studied the relationship between the effects of acupuncture in relieving cerebral ischemia-induced sequelae and the stimulating parameters. The acupuncture stimulating parameter includes the frequency of electroacupuncture (EA), the frequency of acupuncture treatment, and the acquired quantity of stimulation, etc for clinical patients and experimental animals. It was found that different stimulating parameters may have different efficacies. Current research results provide a good basis not only for analysis of the factors of acupuncture-produced effects, but also for determination of the optimal combination of stimulating parameters. However, acupuncture therapeutic effect involves multiple factors and multiple levels, and current quantitative acupuncture parameter researches have been mainly restricted to animal experiments. Hence, more researches in which statistics specialists take part are definitely needed.

34 CFR 350.5 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... expected to require multiple vocational rehabilitation services over an extended period of time; and (iii..., hemiplegia, hemophilia, respiratory or pulmonary dysfunction, mental retardation, mental illness, multiple sclerosis, muscular dystrophy, musculoskeletal disorders, neurological disorders (including stroke and...

34 CFR 350.5 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... expected to require multiple vocational rehabilitation services over an extended period of time; and (iii..., hemiplegia, hemophilia, respiratory or pulmonary dysfunction, mental retardation, mental illness, multiple sclerosis, muscular dystrophy, musculoskeletal disorders, neurological disorders (including stroke and...

Mumps: a year of enhanced surveillance in Catalonia, Spain.

PubMed

Dominguez, Angela; Oviedo, Manuel; Torner, Nuria; Carmona, Gloria; Costa, Josep; Caylà, Joan; Sala, M Rosa; Barrabeig, Irene; Camps, Neus; Minguell, Sofia; Alvarez, Josep; Godoy, Pere; Jansà, Josep M

2009-05-26

Mumps is a vaccine-preventable disease candidate for elimination. Positive predictive value (PPV) of clinical case definition was assessed. During 2007, 410 suspected cases were reported in Catalonia: 348 fulfilled clinical case definition and 159 were laboratory confirmed. Incidence rate was 4.8 per 100,000 for cases that fulfilled the clinical definition, and 2.2 for laboratory confirmed cases. Global PPV was 44.5%; 38.5% in <15 years and 50% in > or =15 years (p=0.04). Most laboratory confirmed cases (72.3%) received at least one MMR dose. With sustained high MMR coverage, laboratory confirmation is necessary to control the disease and assess vaccine failure.

Clinical relevance of sarcopenia in chronic kidney disease

PubMed Central

Moorthi, Ranjani N.; Avin, Keith G.

2018-01-01

Purpose of review In this article, we review sarcopenia in chronic kidney disease (CKD). We aim to present how definitions of sarcopenia from the general population may pertain to those with CKD, its assessment by clinicians and emerging therapies for sarcopenia in CKD. For this review, we limit our description and recommendations to patients with CKD who are not on dialysis. Recent findings Poorer parameters of lean mass, strength and physical function are associated with worsening patient-centered outcomes such as limiting mobility, falls and mortality in CKD; however, the magnitude of these associations are different in those with and without CKD. Sarcopenia in CKD is a balance between skeletal muscle regeneration and catabolism, which are both altered in the uremic environment. Multiple pathways are involved in these derangements, which are briefly reviewed. Differences between commonly used terms cachexia, frailty, protein-energy wasting, dynapenia and sarcopenia are described. Therapeutic options in predialysis CKD are not well studied; therefore, we review exercise options and emerging pharmacological therapies. Summary Sarcopenia, now with its own International Classification of Diseases, 10th Revision (ICD-10) code, is of importance clinically and should be accounted for in research studies in patients with CKD. Multiple therapies for sarcopenia are in development and will hopefully be available for our patients in the future. PMID:28198733

Message Processing Research from Psychology to Communication.

ERIC Educational Resources Information Center

Basil, Michael D.

Information processing theories have been very useful in psychology. The application of information processing literature to communication, however, requires definitions of audiences and definitions of messages relevant to information-processing theories. In order to establish the relevant aspect of audiences, a multiple-stage model of audiences…

Blackboard architecture for medical image interpretation

NASA Astrophysics Data System (ADS)

Davis, Darryl N.; Taylor, Christopher J.

1991-06-01

There is a growing interest in using sophisticated knowledge-based systems for biomedical image interpretation. We present a principled attempt to use artificial intelligence methodologies in interpreting lateral skull x-ray images. Such radiographs are routinely used in cephalometric analysis to provide quantitative measurements useful to clinical orthodontists. Manual and interactive methods of analysis are known to be error prone and previous attempts to automate this analysis typically fail to capture the expertise and adaptability required to cope with the variability in biological structure and image quality. An integrated model-based system has been developed which makes use of a blackboard architecture and multiple knowledge sources. A model definition interface allows quantitative models, of feature appearance and location, to be built from examples as well as more qualitative modelling constructs. Visual task definition and blackboard control modules allow task-specific knowledge sources to act on information available to the blackboard in a hypothesise and test reasoning cycle. Further knowledge-based modules include object selection, location hypothesis, intelligent segmentation, and constraint propagation systems. Alternative solutions to given tasks are permitted.

The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

PubMed

Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

2013-01-01

There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

Functional recovery in patients with schizophrenia: recommendations from a panel of experts.

PubMed

Lahera, Guillermo; Gálvez, José L; Sánchez, Pedro; Martínez-Roig, Miguel; Pérez-Fuster, J V; García-Portilla, Paz; Herrera, Berta; Roca, Miquel

2018-06-05

The management of schizophrenia is evolving towards a more comprehensive model based on functional recovery. The concept of functional recovery goes beyond clinical remission and encompasses multiple aspects of the patient's life, making it difficult to settle on a definition and to develop reliable assessment criteria. In this consensus process based on a panel of experts in schizophrenia, we aimed to provide useful insights on functional recovery and its involvement in clinical practice and clinical research. After a literature review of functional recovery in schizophrenia, a scientific committee of 8 members prepared a 75-item questionnaire, including 6 sections: (I) the concept of functional recovery (9 items), (II) assessment of functional recovery (23 items), (III) factors influencing functional recovery (16 items), (IV) psychosocial interventions and functional recovery (8 items), (V) pharmacological treatment and functional recovery (14 items), and (VI) the perspective of patients and their relatives on functional recovery (5 items). The questionnaire was sent to a panel of 53 experts, who rated each item on a 9-point Likert scale. Consensus was achieved in a 2-round Delphi dynamics, using the median (interquartile range) scores to consider consensus in either agreement (scores 7-9) or disagreement (scores 1-3). Items not achieving consensus in the first round were sent back to the experts for a second consideration. After the two recursive rounds, consensus was achieved in 64 items (85.3%): 61 items (81.3%) in agreement and 3 (4.0%) in disagreement, all of them from section II (assessment of functional recovery). Items not reaching consensus were related to the concepts of functional recovery (1 item, 1.3%), functional assessment (5 items, 6.7%), factors influencing functional recovery (3 items, 4.0%), and psychosocial interventions (2 items, 5.6%). Despite the lack of a well-defined concept of functional recovery, we identified a trend towards a common archetype of the definition and factors associated with functional recovery, as well as its applicability in clinical practice and clinical research.

[Research progress on the clinical value of Ki-67 in breast cancer and its cut-off definition].

PubMed

Chen, Qing; Wu, Kejin

2015-08-01

Ki-67 has an important application value in clinical practice. However, it is still a little tough in clinical application because of the debate on the cut-off definition of Ki-67 index. This review summarizes most studies on the prognostic and predictive value of Ki-67, analyzes the reasons for the discrepancies among the studies cited, and presents the necessity and clinical significance of scientifically defining the cut-off of Ki-67 index, providing a theoretical basis for Ki-67 in clinical application.

Satellite Lesions in Congenital Melanocytic Nevi—Time for a Change of Name

PubMed Central

KINSLER, VERONICA

2011-01-01

Abstract The term “satellite lesions” is used in many conditions in dermatology, generally to describe smaller lesions near the edges of a principal lesion. An online medical dictionary gives the definition “a smaller lesion accompanying a main one and situated nearby,” and this can apply both macroscopically and microscopically. The implication is that the smaller lesions have spread from the parent lesion. Given this definition and usual understanding of the term its use is not apt in the case of congenital melanocytic nevi (CMN). In the vast majority of cases where the patient is said to have satellite lesions these are not restricted to the area around or near the edge of the principal lesion, and are not necessarily significantly smaller. It seems likely that the early use of the term in this condition is an adaptation of the established and correct use in the context of melanoma. Not only is the term not apt clinically but has no known etiological basis. This leaves us with the question of what to call these lesions in cases of CMN. This proposal is to categorise cases into single or multiple CMN, where multiple is 2 or more nevi of any size at birth. An accurate count or good estimate of the number of lesions at birth should also be recorded, and the largest lesion classified as usual with respect to projected adult size. PMID:21418289

Critical care in the surgical global period.

PubMed

Painter, Julie R

2013-03-01

This article explores the rules and regulations from Current Procedural Terminology (CPT) code set and US Medicare and Medicaid Services (Medicare) regarding multiple physicians reporting critical care services during the global period. The article takes into account the critical care definitions, regulations, documentation requirements, and services each provider can report to Medicare. A clinical scenario based on literature supporting the types of complications and care that might typically be included in the post-operative period for a patient who is surgically treated for a type A aortic dissection was analyzed. It was determined that multiple physicians may provide critical care services to a single patient during the global period. The physician who performed the primary procedure cannot report critical care separately unless documentation supporting use of modifier 25 (significant, separately identifiable services) or 24 (unrelated services) supports that critical care is unrelated to the global period. Other physicians may report critical care services separately if specific criteria are met. To report critical care services to Medicare, the patient's condition must meet the Medicare definition of critical care and the physicians should generally represent different specialties providing different aspects of care to the critically ill or injured patient as defined by Medicare. There should be no overlap in time of services provided by each physician. Each physician's documentation should clearly support medical necessity with the diagnosis demonstrating the critical nature of the patients' illness, the total time spent providing critical care, the critical care service provided, and other contributing factors.

Intervening to reduce the risk of future disability from multiple sclerosis: are we there yet?

PubMed

Dahdaleh, Maurice; Alroughani, Raed; Aljumah, Mohammed; AlTahan, Abdulrahman; Alsharoqi, Issa; Bohlega, Saeed A; Daif, Abdulkader; Deleu, Dirk; Inshasi, Jihad; Karabudak, Rana; Sahraian, Mohammed A; Taha, Karim; Yammout, Bassem I; Zakaria, Magd

2017-10-01

Disease-modifying therapies (DMTs) delay or may prevent the progression of patients with high-risk clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), and from relapsing-remitting MS to secondary progressive MS. Current evidence on the effects of DMT on disability in MS is supported by the use of the Expanded Disability Status Scale (EDSS), which is dominated by ambulation, and usually used as a secondary outcome measure. Less is known about the long-term effects of DMTs on other aspects of functional status, particularly cognition, which is a key determinant of ability to work. The time scale for measurements of disability is at most a few years, with scant data from more than 10 years of observation. Longer prospective follow-up of large numbers of patients with CIS is needed to determine whether early intervention with a DMT influences long-term disease progression. Finally, the emergence of the radiologically isolated syndrome (RIS) as a clinical entity has shifted the debate about when to intervene to an even earlier time frame. Balancing the significant side-effects associated with DMT in general and the expected outcome of pharmacologic intervention is increasingly problematic for managing patients with uncertain prognosis, as many patients may have low-risk CIS, benign MS or patients with RIS only. Preventing long-term disability in MS should be recognised more clearly as an important outcome in its own right, with disability measured more consistently with more sensitive instruments beyond the use of the EDSS.

A multimedia electronic patient record (ePR) system to improve decision support in pre- and rehabilitation through clinical and movement analysis

NASA Astrophysics Data System (ADS)

Liu, Brent; Documet, Jorge; McNitt-Gray, Sarah; Requejo, Phil; McNitt-Gray, Jill

2011-03-01

Clinical decisions for improving motor function in patients both with disability as well as improving an athlete's performance are made through clinical and movement analysis. Currently, this analysis facilitates identifying abnormalities in a patient's motor function for a large amount of neuro-musculoskeletal pathologies. However definitively identifying the underlying cause or long-term consequences of a specific abnormality in the patient's movement pattern is difficult since this requires information from multiple sources and formats across different times and currently relies on the experience and intuition of the expert clinician. In addition, this data must be persistent for longitudinal outcomes studies. Therefore a multimedia ePR system integrating imaging informatics data could have a significant impact on decision support within this clinical workflow. We present the design and architecture of such an ePR system as well as the data types that need integration in order to develop relevant decision support tools. Specifically, we will present two data model examples: 1) A performance improvement project involving volleyball athletes and 2) Wheelchair propulsion evaluation of patients with disabilities. The end result is a new frontier area of imaging informatics research within rehabilitation engineering and biomechanics.

Acute kidney injury—an overview of diagnostic methods and clinical management

PubMed Central

Hertzberg, Daniel; Rydén, Linda; Pickering, John W.; Sartipy, Ulrik

2017-01-01

Abstract Acute kidney injury (AKI) is a common condition in multiple clinical settings. Patients with AKI are at an increased risk of death, over both the short and long term, and of accelerated renal impairment. As the condition has become more recognized and definitions more unified, there has been a rapid increase in studies examining AKI across many different clinical settings. This review focuses on the classification, diagnostic methods and clinical management that are available, or promising, for patients with AKI. Furthermore, preventive measures with fluids, acetylcysteine, statins and remote ischemic preconditioning, as well as when dialysis should be initiated in AKI patients are discussed. The classification of AKI includes both changes in serum creatinine concentrations and urine output. Currently, no kidney injury biomarkers are included in the classification of AKI, but proposals have been made to include them as independent diagnostic markers. Treatment of AKI is aimed at addressing the underlying causes of AKI, and at limiting damage and preventing progression. The key principles are: to treat the underlying disease, to optimize fluid balance and optimize hemodynamics, to treat electrolyte disturbances, to discontinue or dose-adjust nephrotoxic drugs and to dose-adjust drugs with renal elimination. PMID:28616210

What do we (not) know about how paracetamol (acetaminophen) works?

PubMed

Toussaint, K; Yang, X C; Zielinski, M A; Reigle, K L; Sacavage, S D; Nagar, S; Raffa, R B

2010-12-01

Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Causes of poor performance of horses during training, racing, or showing: 348 cases (1992-1996).

PubMed

Martin, B B; Reef, V B; Parente, E J; Sage, A D

2000-02-15

To determine results for horses undergoing a high-speed treadmill examination, including videoendoscopy of the pharynx and larynx before and during exercise, echocardiography before and after exercise, and electrocardiography before, during, and after exercise, because of poor performance. Retrospective study. 348 horses. A definitive diagnosis was obtained for 256 (73.5%) horses. One hundred forty-eight horses had dynamic obstruction of the airway during exercise, 33 had clinically important cardiac arrhythmias alone, 22 had a combination of dynamic airway obstruction and clinically important cardiac arrhythmias, 19 had poor cardiac fractional shortening immediately after exercise, 10 had exertional rhabdomyolyis, 15 had clinically apparent lameness, and 9 had other disorders. Thirty-nine of the horses with dynamic obstruction of the airway during exercise had multiple airway abnormalities. Fifty-three horses also had subclinical myopathy Results suggest that a complete evaluation, including a high-speed treadmill examination, should be conducted in horses with poor performance, regardless or whether horses do or do not have a history of abnormal respiratory noises and particularly if the horses have grade-II or -III left laryngeal hemiplegia.

Tuberculous meningitis: a uniform case definition for use in clinical research.

PubMed

Marais, Suzaan; Thwaites, Guy; Schoeman, Johan F; Török, M Estée; Misra, Usha K; Prasad, Kameshwar; Donald, Peter R; Wilkinson, Robert J; Marais, Ben J

2010-11-01

Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, South Africa, and was attended by 41 international participants experienced in the research or management of tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical research. We present the consensus case definition together with the rationale behind the recommendations. This case definition is applicable irrespective of the patient's age, HIV infection status, or the resources available in the research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific communication, and ultimately improve care. Copyright © 2010 Elsevier Ltd. All rights reserved.

Health Sciences Librarians and Education: Clinical Librarianship, Consortia, Extraterrestial Telemedicine

ERIC Educational Resources Information Center

Cummings, Polly; And Others

1978-01-01

Three speeches presented by a panel of health science librarians discuss: (1) clinical medical librarianship, with a definition and descriptions of programs in several medical school libraries; (2) consortia, including a definition and reasons for their development; and (3) use of telecommunications for sharing medical information. (MBR)

38 CFR 51.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... NURSING HOME CARE OF VETERANS IN STATE HOMES General § 51.2 Definitions. For purposes of this part: Clinical nurse specialist means a licensed professional nurse who has a Master's degree in nursing with a major in a clinical nursing specialty from an academic program accredited by the National League for...

38 CFR 51.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... NURSING HOME CARE OF VETERANS IN STATE HOMES General § 51.2 Definitions. For purposes of this part: Clinical nurse specialist means a licensed professional nurse who has a Master's degree in nursing with a major in a clinical nursing specialty from an academic program accredited by the National League for...

38 CFR 51.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... NURSING HOME CARE OF VETERANS IN STATE HOMES General § 51.2 Definitions. For purposes of this part: Clinical nurse specialist means a licensed professional nurse who has a Master's degree in nursing with a major in a clinical nursing specialty from an academic program accredited by the National League for...

38 CFR 51.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... NURSING HOME CARE OF VETERANS IN STATE HOMES General § 51.2 Definitions. For purposes of this part: Clinical nurse specialist means a licensed professional nurse who has a Master's degree in nursing with a major in a clinical nursing specialty from an academic program accredited by the National League for...

38 CFR 51.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... NURSING HOME CARE OF VETERANS IN STATE HOMES General § 51.2 Definitions. For purposes of this part: Clinical nurse specialist means a licensed professional nurse who has a Master's degree in nursing with a major in a clinical nursing specialty from an academic program accredited by the National League for...

Defining Research: The Effect of Linguistic Choices on the Intentions to Participate in Clinical Research.

PubMed

Strekalova, Yulia A

2017-06-01

Significant barriers to participant recruitment for clinical research (CR) are related to effective communication, and nurse coordinators are entrusted with being knowledge brokers between investigators and prospective participants. This prospective cohort study sought to identify linguistic choices that could inform and facilitate recruitment efforts. Healthy adults ( N = 204) were invited to join an online survey to assess the likelihood of participation in CR based on short and extended definitions of CR. Five short definitions included clinical trial, clinical study, health-related research study, community participatory study, and quality improvement study. The likelihood of participation in CR was the lowest for clinical trial and the highest for health-related research study. However, when only an extended definition was provided, those differences were not observed. A linguistic change from trial to study could lead to positive attitude toward CR and improvements in recruitment. However, ethical implications of linguistic choices should be considered.

Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia.

PubMed

Walsh, Michele C; Wilson-Costello, Deanna; Zadell, Arlene; Newman, Nancy; Fanaroff, Avroy

2003-09-01

Bronchopulmonary dysplasia (BPD) is the focus of many intervention trials, yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians. Thus, we wished to define BPD by a standardized oxygen saturation monitoring at 36 weeks corrected age, and compare this physiologic definition with the standard clinical definition of BPD based solely on oxygen administration. A total of 199 consecutive very low birthweight infants (VLBW, 501 to 1500 g birthweight) were assessed prospectively at 36+/-1 weeks corrected age. Neonates on positive pressure support or receiving >30% supplemental oxygen were assigned the outcome BPD. Those receiving < or =30% oxygen underwent a stepwise 2% reduction in supplemental oxygen to room air while under continuous observation and oxygen saturation monitoring. Outcomes of the test were "no BPD" (saturations > or =88% for 60 minutes) or "BPD" (saturation < 88%). At the conclusion of the test, all infants were returned to their baseline oxygen. Safety (apnea, bradycardia, increased oxygen use), inter-rater reliability, test-retest reliability, and validity of the physiologic definition vs the clinical definition were assessed. A total of 199 VLBW were assessed, of whom 45 (36%) were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks corrected age. The physiologic definition identified 15 infants treated with oxygen who successfully passed the saturation monitoring test in room air. The physiologic definition diagnosed BPD in 30 (24%) of the cohort. All infants were safely studied. The test was highly reliable (inter-rater reliability, kappa=1.0; test-retest reliability, kappa=0.83) and highly correlated with discharge home in oxygen, length of hospital stay, and hospital readmissions in the first year of life. The physiologic definition of BPD is safe, feasible, reliable, and valid and improves the precision of the diagnosis of BPD. This may be of benefit in future multicenter clinical trials.

Time for a neonatal–specific consensus definition for sepsis

PubMed Central

Wynn, James L.; Wong, Hector R.; Shanley, Thomas P.; Bizzarro, Matthew J.; Saiman, Lisa; Polin, Richard A.

2014-01-01

Objective To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. Study selection The review focused primarily on pediatric literature relevant to the topic of interest. Conclusions Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates. PMID:24751791

12 CFR 583.12 - Multiple savings and loan holding company.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Multiple savings and loan holding company. 583.12 Section 583.12 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING SAVINGS AND LOAN HOLDING COMPANIES § 583.12 Multiple savings and loan...

The Mayan Activity: A Way of Teaching Multiple Quantifications in Logical Contexts

ERIC Educational Resources Information Center

Roh, Kyeong Hah; Lee, Yong Hah

2011-01-01

In this article, we suggest an instructional intervention to help students understand statements involving multiple quantifiers in logical contexts. We analyze students' misinterpretations of multiple quantifiers related to the epsilon-N definition of convergence and point out that they result from a lack of understanding of the significance of…

Seroprevalence, isolation, and co-infection of multiple Toxoplasma gondii strains in individual bobcats (Lynx rufus) from Mississippi, USA

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii causes lifelong chronic infection in both feline definitive hosts and intermediate hosts. Multiple exposures of the parasite are likely to occur in nature because of high environmental contamination. Here, we present data of high seroprevalence and multiple T. gondii strain co-infe...

Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.

PubMed

Burgers, Leonie E; Siljehult, Filip; Ten Brinck, Robin M; van Steenbergen, Hanna W; Landewé, Robert B M; Rantapää-Dahlqvist, Solbritt; van der Helm-van Mil, Annette H M

2017-12-01

Recently a EULAR-taskforce defined arthralgia suspicious for progression to RA, in order to allow inclusion of homogeneous sets of arthralgia patients in clinical studies. This longitudinal study aimed (i) to validate this definition in arthralgia patients in whom rheumatologists felt that imminent RA was more likely than other arthralgias [clinically suspect arthralgia (CSA)], that is, the target population fulfilling the entry criterion, and (ii) to explore the performance in arthralgia patients who were referred to secondary care prior to rheumatological evaluation, hence ignoring the entry criterion. The definition was assessed in 241 Dutch patients identified with CSA by rheumatologists and 113 patients referred to the Umeå university hospital with recent-onset arthralgia in small joints. The external reference was arthritis development <2 years' follow-up. CSA patients with a positive definition (⩾3/7 parameters present) had an increased risk for developing arthritis compared with definition-negative CSA patients (hazard ratio = 2.1, 95% CI: 0.9, 4.7). The sensitivity was 84% and the positive predictive value 30%. In arthralgia patients in whom the definition was applied before rheumatological evaluation, a positive definition was neither sensitive (10%) nor predictive (positive predictive value 3%). The EULAR definition of arthralgia suspicious for progression to RA is sensitive when used to support the rheumatologist's opinion on imminent RA. This validation study shows that the definition, when used as designed, further homogenizes patients that rheumatologists consider at risk for RA. To arrive at a high specificity, the clinical definition needs to be combined with biomarkers. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

PubMed

Garcia-Garcia, Hector M; McFadden, Eugène P; Farb, Andrew; Mehran, Roxana; Stone, Gregg W; Spertus, John; Onuma, Yoshinobu; Morel, Marie-Angèle; van Es, Gerrit-Anne; Zuckerman, Bram; Fearon, William F; Taggart, David; Kappetein, Arie-Pieter; Krucoff, Mitchell W; Vranckx, Pascal; Windecker, Stephan; Cutlip, Donald; Serruys, Patrick W

2018-06-14

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

The design and methodology of premature ejaculation interventional studies

PubMed Central

2016-01-01

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials. PMID:27652224

Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition.

PubMed

Cummings, Jeffrey; Mintzer, Jacobo; Brodaty, Henry; Sano, Mary; Banerjee, Sube; Devanand, D P; Gauthier, Serge; Howard, Robert; Lanctôt, Krista; Lyketsos, Constantine G; Peskind, Elaine; Porsteinsson, Anton P; Reich, Edgardo; Sampaio, Cristina; Steffens, David; Wortmann, Marc; Zhong, Kate

2015-01-01

Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.

Objective Sepsis Surveillance Using Electronic Clinical Data

PubMed Central

Rhee, Chanu; Kadri, Sameer; Huang, Susan S.; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael

2016-01-01

OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health record–based surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definition’s accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 2003–2012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health record–based clinical surveillance definition had stable and high sensitivity over time (77% in 2003–2009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 2003–2009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%–88%) and absolute mortality declined by 5.4% (95% CI, 4.6%–6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, −1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%–2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends. PMID:26526737

Obsessionality & compulsivity: a phenomenology of obsessive-compulsive disorder.

PubMed

Denys, Damiaan

2011-02-01

Progress in psychiatry depends on accurate definitions of disorders. As long as there are no known biologic markers available that are highly specific for a particular psychiatric disorder, clinical practice as well as scientific research is forced to appeal to clinical symptoms. Currently, the nosology of obsessive-compulsive disorder is being reconsidered in view of the publication of DSM-V. Since our diagnostic entities are often simplifications of the complicated clinical profile of patients, definitions of psychiatric disorders are imprecise and always indeterminate. This urges researchers and clinicians to constantly think and rethink well-established definitions that in psychiatry are at risk of being fossilised. In this paper, we offer an alternative view to the current definition of obsessive-compulsive disorder from a phenomenological perspective. TRANSLATION: This article is translated from Dutch, originally published in [Handbook Obsessive-compulsive disorders, Damiaan Denys, Femke de Geus (Eds.), (2007). De Tijdstroom uitgeverij BV, Utrecht. ISBN13: 9789058980878.].

Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies.

PubMed

Tzikas, Apostolos; Holmes, David R; Gafoor, Sameer; Ruiz, Carlos E; Blomström-Lundqvist, Carina; Diener, Hans-Christoph; Cappato, Riccardo; Kar, Saibal; Lee, Randal J; Byrne, Robert A; Ibrahim, Reda; Lakkireddy, Dhanunjaya; Soliman, Osama I; Nabauer, Michael; Schneider, Steffen; Brachmann, Johannes; Saver, Jeffrey L; Tiemann, Klaus; Sievert, Horst; Camm, A John; Lewalter, Thorsten

2017-01-01

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

A Practical Approach to Governance and Optimization of Structured Data Elements.

PubMed

Collins, Sarah A; Gesner, Emily; Morgan, Steven; Mar, Perry; Maviglia, Saverio; Colburn, Doreen; Tierney, Diana; Rocha, Roberto

2015-01-01

Definition and configuration of clinical content in an enterprise-wide electronic health record (EHR) implementation is highly complex. Sharing of data definitions across applications within an EHR implementation project may be constrained by practical limitations, including time, tools, and expertise. However, maintaining rigor in an approach to data governance is important for sustainability and consistency. With this understanding, we have defined a practical approach for governance of structured data elements to optimize data definitions given limited resources. This approach includes a 10 step process: 1) identification of clinical topics, 2) creation of draft reference models for clinical topics, 3) scoring of downstream data needs for clinical topics, 4) prioritization of clinical topics, 5) validation of reference models for clinical topics, and 6) calculation of gap analyses of EHR compared against reference model, 7) communication of validated reference models across project members, 8) requested revisions to EHR based on gap analysis, 9) evaluation of usage of reference models across project, and 10) Monitoring for new evidence requiring revisions to reference model.

Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes.

PubMed

Nanchen, David; Gencer, Baris; Muller, Olivier; Auer, Reto; Aghlmandi, Soheila; Heg, Dik; Klingenberg, Roland; Räber, Lorenz; Carballo, David; Carballo, Sebastian; Matter, Christian M; Lüscher, Thomas F; Windecker, Stephan; Mach, François; Rodondi, Nicolas

2016-09-06

Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07-5.65; P=0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46-5.11; P=0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26-9.94; P=0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins. © 2016 American Heart Association, Inc.

Case definition for progressive multifocal leukoencephalopathy following treatment with monoclonal antibodies.

PubMed

Mentzer, Dirk; Prestel, Jürgen; Adams, Ortwin; Gold, Ralf; Hartung, Hans-Peter; Hengel, Hartmut; Kieseier, Bernd C; Ludwig, Wolf-Dieter; Keller-Stanislawski, Brigitte

2012-09-01

Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for PML is a prerequisite for a thorough assessment of PML. A working group was established to develop a standardised case definition for PML which permits data comparability across clinical trials, postauthorisation safety studies and passive postmarketing surveillance. The case definition is designed to define levels of diagnostic certainty of reported PML cases following treatment with MABs. It was subsequently used to categorise retrospectively suspected PML cases from Germany reported to the Paul-Ehrlich-Institute as the responsible national competent authority. The algorithm of the case definition is based on clinical symptoms, PCR for JC virus DNA in cerebrospinal fluid, brain MRI, and brain biopsy/autopsy. The case definition was applied to 119 suspected cases of PML following treatment with MABs and is considered to be helpful for case ascertainment of suspected PML cases for various MABs covering a broad spectrum of indications. Even if the available information is not yet complete, the case definition provides a level of diagnostic certainty. The proposed case definition permits data comparability among different medicinal products and among active as well as passive surveillance settings. It may form a basis for meaningful risk analysis and communication for regulators and healthcare professionals.

Traumatic brain injury: It is all about definition.

PubMed

Savitsky, B; Givon, A; Rozenfeld, M; Radomislensky, I; Peleg, K

2016-01-01

TBI may be defined by different methods. Some may be most useful for immediate clinical purposes, however less optimal for epidemiologic research. Other methods, such as the Abbreviated Injury Score (AIS), may prove more beneficial for this task, if the cut-off-points for their categories are defined correctly. To reveal the optimal cut-off-points for AIS in definition of severity of TBI in order to ensure uniformity between future studies of TBI. Mortality of patients with TBI AIS 3, 4 was 1.9% and 2.9% respectively, comparing with 31.1% among TBI AIS 5+. Predictive discrimination ability of the model with cut-off-points of 5+ for TBI AIS (in comparison with other cut-off-points) was better. Patients with missing Glasgow Coma Scale (GCS) in the ED had an in-hospital mortality rate of 11.5%. In this group, 25% had critical TBI according to AIS. Normal GCS didn't indicate an absence of head injury, as, among patients with GCS 15 in the ED, 26% had serious/critical TBI injury. Moreover, 7% of patients with multiple injury and GCS 3-8 had another reason than head injury for unconsciousness. This study recommends the adoption of an AIS cut-off ≥ 5 as a valid definition of severe TBI in epidemiological studies, while AIS 3-4 may be defined as 'moderate' TBI and AIS 1-2 as 'mild'.

Metabolic risk profiles created using cluster analysis are differentially associated with physical activity: The ARIC study

USDA-ARS?s Scientific Manuscript database

Conditions such as hypertension, dyslipidemia, glucose intolerance, and obesity tend to cluster together and predict cardiovascular disease, type 2 diabetes, and premature mortality. This clustering has led to multiple definitions of the Metabolic Syndrome (MetS). While the definitions agree on the ...

[Target volume margins for lung cancer: internal target volume/clinical target volume].

PubMed

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions

PubMed Central

Cavender, Matthew A.; Stone, Gregg W.; White, Harvey D.; Steg, Ph. Gabriel; Gibson, C. Michael; Hamm, Christian W.; Price, Matthew J.; Leonardi, Sergio; Prats, Jayne; Deliargyris, Efthymios N.; Mahaffey, Kenneth W.; Harrington, Robert A.

2016-01-01

BACKGROUND: Cangrelor is an intravenous P2Y12 inhibitor approved to reduce periprocedural ischemic events in patients undergoing percutaneous coronary intervention not pretreated with a P2Y12 inhibitor. METHODS: A total of 11 145 patients were randomized to cangrelor or clopidogrel in the CHAMPION PHOENIX trial (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). We explored the effects of cangrelor on myocardial infarction (MI) using different definitions and performed sensitivity analyses on the primary end point of the trial. RESULTS: A total of 462 patients (4.2%) undergoing percutaneous coronary intervention had an MI as defined by the second universal definition. The majority of these MIs (n=433, 93.7%) were type 4a. Treatment with cangrelor reduced the incidence of MI at 48 hours (3.8% versus 4.7%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67–0.97; P=0.02). When the Society of Coronary Angiography and Intervention definition of periprocedural MI was applied to potential ischemic events, there were fewer total MIs (n=134); however, the effects of cangrelor on MI remained significant (OR, 0.65; 95% CI, 0.46–0.92; P=0.01). Similar effects were seen in the evaluation of the effects of cangrelor on MIs with peak creatinine kinase-MB ≥10 times the upper limit of normal (OR, 0.64; 95% CI, 0.45–0.91) and those with peak creatinine kinase-MB ≥10 times the upper limit of normal, ischemic symptoms, or ECG changes (OR, 0.63; 95% CI, 0.48–0.84). MIs defined by any of these definitions were associated with increased risk of death at 30 days. Treatment with cangrelor reduced the composite end point of death, MI (Society of Coronary Angiography and Intervention definition), ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis (1.4% versus 2.1%; OR, 0.69; 95% CI, 0.51–0.92). CONCLUSIONS: MI in patients undergoing percutaneous coronary intervention, regardless of definition, remains associated with increased risk of death in the current era. Cangrelor compared with clopidogrel significantly reduces MI regardless of the definition. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01156571. PMID:27482008

Comparison of different criteria for periodontitis case definition in head and neck cancer individuals.

PubMed

Bueno, Audrey Cristina; Ferreira, Raquel Conceição; Cota, Luis Otávio Miranda; Silva, Guilherme Carvalho; Magalhães, Cláudia Silami; Moreira, Allyson Nogueira

2015-09-01

Different periodontitis case definitions have been used in clinical research and epidemiology. The aim of this study was to determine more accurate criterion for the definition of mild and moderate periodontitis case to be applied to head and neck cancer individuals before radiotherapy. The frequency of periodontitis in a sample of 84 individuals was determined according to different diagnostic criteria: (1) Lopez et al. (2002);(2) Hujoel et al. (2006); (3) Beck et al. (1990); (4) Machtei et al. (1992); (5) Tonetti and Claffey (2005); (6) and Page and Eke (2007). All diagnosis were based on the clinical parameters obtained by a single calibrated examiner (Kw = 0.71). The individuals were evaluated before radiotherapy. They received oral hygiene instructions, and the cases diagnosed with periodontitis (Page and Eke 2007) were treated. The gold standard was the definition 6, and the others were compared by means of agreement, sensitivity (SS), specificity (SP), and the area under ROC curve. The kappa test evaluated the agreement between definitions. The frequency of periodontitis at baseline was 53.6 % (definition 1), 81.0 % (definition 2), 40.5 % (definition 3), 26.2 % (definition 4), 13.1 % (definition 5), and 70.2 % (definition 6). The kappa test showed a moderate agreement between definitions 6 and 2 (59.0 %) and definitions 6 and 1 (56.0 %). The criterion with higher SS (0.92) and SP (0.73) was definition 1. Definition 1 was the most accurate criterion to case periodontitis definition to be applied to head and neck cancer individuals.

Clinical Criteria Versus a Possible Research Case Definition in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

PubMed Central

Jason, Leonard A.; McManimen, Stephanie; Sunnquist, Madison; Newton, Julia L.; Strand, Elin Bolle

2017-01-01

Background The Institute of Medicine (IOM) recently developed clinical criteria for what had been known as chronic fatigue syndrome (CFS). Given the broad nature of the clinical IOM criteria, there is a need for a research definition that would select a more homogenous and impaired group of patients than the IOM clinical criteria. At the present time, it is unclear what will serve as the research definition. Purpose The current study focused on a research definition which selected homebound individuals who met the four IOM criteria, excluding medical and psychiatric co-morbidities. Methods Our research criteria were compared to those participants meeting the IOM criteria. Those not meeting either of these criteria sets were placed in a separate group defined by 6 or more months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and the SF-36. Due to unequal sample sizes and variances, Welch’s F tests and Games-Howell post hoc tests were conducted. Results Using a large database of over 1,000 patients from several countries, we found that those meeting a more restrictive research definition were even more impaired and more symptomatic than those meeting criteria for the other two groups. Conclusion Deciding on a particular research case definition would allow researchers to select more comparable patient samples across settings, and this would represent one of the most significant methodologic advances for this field of study. PMID:29062593

Of Atkins and men: deviations from clinical definitions of mental retardation in death penalty cases.

PubMed

Blume, John H; Johnson, Sheri Lynn; Seeds, Christopher

2009-01-01

Under Atkins v. Virginia, the Eighth Amendment exempts from execution individuals who meet the clinical definitions of mental retardation set forth by the American Association on Intellectual and Developmental Disabilities and the American Psychiatric Association. Both define mental retardation as significantly subaverage intellectual functioning accompanied by significant limitations in adaptive functioning, originating before the age of 18. Since Atkins, most jurisdictions have adopted definitions of mental retardation that conform to those definitions. But some states, looking often to stereotypes of persons with mental retardation, apply exclusion criteria that deviate from and are more restrictive than the accepted scientific and clinical definitions. These state deviations have the effect of excluding from Atkins's reach some individuals who plainly fall within the class it protects. This article focuses on the cases of Roger Cherry, Jeffrey Williams, Michael Stallings, and others, who represent an ever-growing number of individuals inappropriately excluded from Atkins. Left unaddressed, the state deviations discussed herein permit what Atkins does not: the death-sentencing and execution of some capital defendants who have mental retardation.

Evaluation of the WHO clinical case definition of AIDS among children in India.

PubMed

Gurprit, Grover; Tripti, Pensi; Gadpayle, A K; Tanushree, Banerjee

2008-03-01

The need of a clinical case definition (CCD) for Acquired Immunodeficiency Syndrome (AIDS) was felt by public health agencies to monitor diseases resulting from human immunodeficiency virus (HIV) infection. To test the statistical significance of the existing World Health Organization (WHO) CCD for the diagnosis of AIDS in areas where diagnostic resources are limited in India, a prospective study was conducted in the Paediatrics department at Dr. Ram Manohar Lohia Hospital, New Delhi. 360 cases between 18 months-12 years of age satisfying WHO case definitions of AIDS were included in the study group. Informed consent was taken from the parents. The serum of patients was subjected to ELISA to conform the diagnosis of HIV infection. Our study detected 16.66% (60) of HIV prevalence in children visiting paediatrics outpatient clinic. 20% cases manifested 3 major and 2 minor signs. This definition had a sensitivity of 73.33%, specificity of 90.66%, positive predictive value (PPV) of 61.11% and negative predictive value (NPV) of 94.44%. On using stepwise logistic regression analysis weight loss, chronic fever > 1 month and total lymphocyte count of less than 1500 cells/mm3 emerged as important predictors. Cases showing 2 major and 2 minor signs were 86 (23.89%) with a sensitivity and specificity of 86.66% and 88.66% respectively. Based on these findings, we propose a clinical case definition based on 13 clinical signs and symptoms for paediatric AIDS in India with better sensitivity and PPV than the WHO case definition but with almost similar specificity. Thus multicentric studies are further required to modify these criteria in Indian set up.

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

PubMed

Sokka, Tuulikki; Hetland, Merete Lund; Mäkinen, Heidi; Kautiainen, Hannu; Hørslev-Petersen, Kim; Luukkainen, Reijo K; Combe, Bernard; Badsha, Humeira; Drosos, Alexandros A; Devlin, Joe; Ferraccioli, Gianfranco; Morelli, Alessia; Hoekstra, Monique; Majdan, Maria; Sadkiewicz, Stefan; Belmonte, Miguel; Holmqvist, Ann-Carin; Choy, Ernest; Burmester, Gerd R; Tunc, Recep; Dimić, Aleksander; Nedović, Jovan; Stanković, Aleksandra; Bergman, Martin; Toloza, Sergio; Pincus, Theodore

2008-09-01

To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Multiple Chronic Conditions and Healthcare Costs among Adults

PubMed Central

Sambamoorthi, Usha; Tan, Xi; Deb, Arijita

2015-01-01

The prevalence of multiple chronic conditions (MCC) is increasing among individuals of all ages. MCC are associated with poor health outcomes. The presence of MCC has profound healthcare utilization and cost implications for public and private insurance payers, individuals, and families. Investigators have used a variety of definitions for MCC to evaluate costs associated with MCC. The objective of this article is to examine the current literature in estimating excess costs associated with MCC among adults. The discussion highlights some of the theoretical and technical merits of various MCC definitions and models used to estimate the excess costs associated with MCC. PMID:26400220

Child Emotional Aggression and Abuse: Definitions and Prevalence

ERIC Educational Resources Information Center

Slep, Amy M. Smith; Heyman, Richard E.; Snarr, Jeffery D.

2011-01-01

Objective: Research on and intervention for child emotional abuse and emotional aggression toward children have been severely hampered because there have been no agreed-upon, clinically usable definitions. Methods: We have (a) proposed and field-tested a set of criteria to operationally define child emotional abuse for clinical settings and (b)…

Clinical Social Work Practice and Education: What Would Flexner Think Now?

ERIC Educational Resources Information Center

Tosone, Carol

2016-01-01

A century has passed since Abraham Flexner posed the question on whether social work is a profession. This article attempts to answer that question, and considers several definitions put forth by global and national social work professional organizations, including a definition of clinical social work. Addressing the current state of social work…

Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review.

PubMed

Bartoszko, Justyna; Vorobeichik, Leon; Jayarajah, Mohandas; Karkouti, Keyvan; Klein, Andrew A; Lamy, Andre; Mazer, C David; Murphy, Mike; Richards, Toby; Englesakis, Marina; Myles, Paul S; Wijeysundera, Duminda N

2017-06-30

'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. This scoping review of the previously published literature does not require research ethics approval. The results will be used to inform a consensus-based process to develop definitions of clinically important perioperative blood loss and transfusion. The results of the scoping review will be published in a peer-reviewed scientific journal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An entropy-based nonparametric test for the validation of surrogate endpoints.

PubMed

Miao, Xiaopeng; Wang, Yong-Cheng; Gangopadhyay, Ashis

2012-06-30

We present a nonparametric test to validate surrogate endpoints based on measure of divergence and random permutation. This test is a proposal to directly verify the Prentice statistical definition of surrogacy. The test does not impose distributional assumptions on the endpoints, and it is robust to model misspecification. Our simulation study shows that the proposed nonparametric test outperforms the practical test of the Prentice criterion in terms of both robustness of size and power. We also evaluate the performance of three leading methods that attempt to quantify the effect of surrogate endpoints. The proposed method is applied to validate magnetic resonance imaging lesions as the surrogate endpoint for clinical relapses in a multiple sclerosis trial. Copyright © 2012 John Wiley & Sons, Ltd.

[Shift work and night work: what effect on blood pressure?].

PubMed

Cassat, M; Wuerzner, G; Burnier, M

2015-09-09

Shift work has become more and more common for the last thirty years. By definition, shift work disturbs the circadian rhythm and the internal clock. Even if the pathophysiological mechanisms are not well understood, a greater cardiovascular risk has been attributed to shift work. Cross-sectional and cohort studies have identified an association between shift work and an elevated blood pressure. Shift workers also present a higher incidence of hypertension and progression than day workers. Unfortunately, the heterogeneity of the studies, the multiple confounding factors, as well as the complexity to achieve a suitable comparison group make it impossible to draw firm clinical evidence. Nevertheless, this population needs a medical follow-up focused on the cardiovascular risks and blood pressure.

Proposing a New Conceptual Model and an Exemplar Measure Using Health Information: Technology to Examine the Impact of Relational Nurse Continuity on Hospital-Acquired Pressure Ulcers

PubMed Central

STIFTER, Janet; YAO, Yingwei; LOPEZ, Karen Dunn; KHOKHAR, Ashfaq; WILKIE, Diana J.; KEENAN, Gail M.

2015-01-01

The influence of the staffing variable nurse continuity on patient outcomes has been rarely studied and with inconclusive results. Multiple definitions and an absence of systematic methods for measuring the influence of continuity have resulted in its exclusion from nurse-staffing studies and conceptual models. We present a new conceptual model and an innovative use of health information technology to measure nurse continuity and to demonstrate the potential for bringing the results of big data science back to the bedside. Understanding the power of big data to address critical clinical issues may foster a new direction for nursing administration theory development. PMID:26244480

Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

PubMed

Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

2015-01-01

Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

Development of a clinical definition for acute respiratory distress syndrome using the Delphi technique.

PubMed

Ferguson, Niall D; Davis, Aileen M; Slutsky, Arthur S; Stewart, Thomas E

2005-06-01

The objective of this study is to describe the implementation of formal consensus techniques in the development of a clinical definition for acute respiratory distress syndrome. A Delphi consensus process was conducted using e-mail. Sixteen panelists who were both researchers and opinion leaders were systematically recruited. The Delphi technique was performed over 4 rounds on the background of an explicit definition framework. Item generation was performed in round 1, item reduction in rounds 2 and 3, and definition evaluation in round 4. Explicit consensus thresholds were used throughout. Of the 16 panelists, 11 actually participated in developing a definition that met a priori consensus rules on the third iteration. New incorporations in the Delphi definition include the use of a standardized oxygenation assessment and the documentation of either a predisposing factor or decreased thoracic compliance. The panelists rated the Delphi definition as acceptable to highly acceptable (median score, 6; range, 5-7 on a 7-point Likert scale). We conclude that it is feasible to consider using formal consensus in the development of future definitions of acute respiratory distress syndrome. Testing of sensibility, reliability, and validity are needed for this preliminary definition; these test results should be incorporated into future iterations of this definition.

Emotional and Behavioral Disorders in South Korea: Current Status and Issues

ERIC Educational Resources Information Center

Kim, Joungmin; Kim, Kyeong-hwa

2016-01-01

In South Korea, there is no consensus on the definition of emotional and behavioral disorders (EBD). This column focuses on how the definition has affected the prevalence rates and services available for students with EBDs. Of the legal, clinical, and educational definitions, the legal definition of EBDs is currently in common use, which raises…

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

PubMed

Di Filippo, M; Anderson, V M; Altmann, D R; Swanton, J K; Plant, G T; Thompson, A J; Miller, D H

2010-02-01

Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

The Multiple-Car Method. Exploring Its Use in Driver and Traffic Safety Education. Second Edition.

ERIC Educational Resources Information Center

American Driver and Traffic Safety Education Association, Washington, DC.

Primarily written for school administrators and driver education teachers, this publication presents information on planning and implementing the multiple car method of driver instruction. An introductory section presents a definition of the multiple car method and its history of development. It is defined as an off-street paved area incorporating…

Application of the McDonald MRI criteria in multiple sclerosis.

PubMed

Chan, Ling Ling; Sitoh, Yih Yian; Chong, June; See, Siew Ju; Umapathi, Thirugnanam N; Lim, Shih Hui; Ong, Benjamin

2007-08-01

The aim of this study was to assess the sensitivity of McDonald's magnetic resonance imaging (MRI) criteria for the diagnosis of multiple sclerosis (MS) in a group of Asian patients diagnosed with clinically definite MS, based on lesion characterisation on MRI scans. Forty-nine patients from 3 major neurological institutions were classified as having Asian- or Western-type MS based on clinical assessment. Each MRI scan was reviewed by 2 neuroradiologists for the presence and characteristics of brain and spinal lesions. The McDonald's MRI criteria were then applied and its sensitivity evaluated. Nine patients were excluded, leaving 34 females and 6 males who were dominantly Chinese (90%), with a mean age of 36.2 years. The MRI brain and spinal findings were detailed and tabulated. Statistically significant differences (P <0.01) in MRI brain findings and sensitivity of McDonald's MRI criteria were found between our Asian- and Western-type MS patients. The diagnostic yield of McDonald's MRI criteria increased by 20% when we substituted a cord for a brain lesion, and applied the substitution for enhancing cord lesions as well. The diagnosis is more likely to be made when using McDonald MRI criteria based on brain findings, in a patient who presents clinically with Western-type MS. The provision for substitution of "one brain for a spinal lesion" is helpful in Asian-type MS, where there is preponderance of spinal lesion load. Our findings suggest that minor modifications in the interpretation of McDonald's MRI criteria have significant impact on the diagnosis in patients clinically presenting as Asian-type MS, with potential bearing on their subsequent management.

[Application of second generation dual-source computed tomography dual-energy scan mode in detecting pancreatic adenocarcinoma].

PubMed

Xue, Hua-dan; Liu, Wei; Sun, Hao; Wang, Xuan; Chen, Yu; Su, Bai-yan; Sun, Zhao-yong; Chen, Fang; Jin, Zheng-yu

2010-12-01

To analyze the clinical value of multiple sequences derived from dual-source computed tomography (DSCT) dual-energy scan mode in detecting pancreatic adenocarcinoma. Totally 23 patients with clinically or pathologically diagnosed pancreatic cancer were enrolled in this retrospective study. DSCT (Definition Flash) was used and dual-energy scan mode was used in their pancreatic parenchyma phase scan (100kVp/230mAs and Sn140kVp/178mAs) . Mono-energetic 60kev, mono-energetic 80kev, mono-energetic 100kev, mono-energetic 120kev, linear blend image, non-linear blend image, and iodine map were acquired. pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were calculated. One-way ANOVA was used for the comparison of diagnostic values of the above eight different dual-energy derived sequences for pancreatic cancer. The pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were significantly different among eight sequences (P<0.05) . Mono-energetic 60kev image showed the largest parenchyma-tumor CT value [ (77.53 ± 23.42) HU] , and iodine map showed the lowest tumor/parenchyma enhancement ratio (0.39?0.12) and the largest contrast to noise ratio (4.08 ± 1.46) . Multiple sequences can be derived from dual-energy scan mode with DSCT via multiple post-processing methods. Integration of these sequences may further improve the sensitivity of the multislice spiral CT in the diagnosis of pancreatic cancer.

Case definition and classification of leukodystrophies and leukoencephalopathies.

PubMed

Vanderver, Adeline; Prust, Morgan; Tonduti, Davide; Mochel, Fanny; Hussey, Heather M; Helman, Guy; Garbern, James; Eichler, Florian; Labauge, Pierre; Aubourg, Patrick; Rodriguez, Diana; Patterson, Marc C; Van Hove, Johan L K; Schmidt, Johanna; Wolf, Nicole I; Boespflug-Tanguy, Odile; Schiffmann, Raphael; van der Knaap, Marjo S

2015-04-01

An approved definition of the term leukodystrophy does not currently exist. The lack of a precise case definition hampers efforts to study the epidemiology and the relevance of genetic white matter disorders to public health. Thirteen experts at multiple institutions participated in iterative consensus building surveys to achieve definition and classification of disorders as leukodystrophies using a modified Delphi approach. A case definition for the leukodystrophies was achieved, and a total of 30 disorders were classified under this definition. In addition, a separate set of disorders with heritable white matter abnormalities but not meeting criteria for leukodystrophy, due to presumed primary neuronal involvement and prominent systemic manifestations, was classified as genetic leukoencephalopathies (gLE). A case definition of leukodystrophies and classification of heritable white matter disorders will permit more detailed epidemiologic studies of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Postoperative Tachycardia: Clinically Meaningful or Benign Consequence of Orthopedic Surgery?

PubMed

Sigmund, Alana E; Fang, Yixin; Chin, Matthew; Reynolds, Harmony R; Horwitz, Leora I; Dweck, Ezra; Iturrate, Eduardo

2017-01-01

To determine the clinical significance of tachycardia in the postoperative period. Individuals 18 years or older undergoing hip and knee arthroplasty were included in the study. Two data sets were collected from different time periods: development data set from January 1, 2011, through December 31, 2011, and validation data set from December 1, 2012, through September 1, 2014. We used the development data set to identify the optimal definition of tachycardia with the strongest association with the vascular composite outcome (pulmonary embolism and myocardial necrosis and infarction). The predictive value of this definition was assessed in the validation data set for each outcome of interest, pulmonary embolism, myocardial necrosis and infarction, and infection using multiple logistic regression to control for known risk factors. In 1755 patients in the development data set, a maximum heart rate (HR) greater than 110 beats/min was found to be the best cutoff as a correlate of the composite vascular outcome. Of the 4621 patients who underwent arthroplasty in the validation data set, 40 (0.9%) had pulmonary embolism. The maximum HR greater than 110 beats/min had an odds ratio (OR) of 9.39 (95% CI, 4.67-18.87; sensitivity, 72.5%; specificity, 78.0%; positive predictive value, 2.8%; negative predictive value, 99.7%) for pulmonary embolism. Ninety-seven patients (2.1%) had myocardial necrosis (elevated troponin). The maximum HR greater than 110 beats/min had an OR of 4.71 (95% CI, 3.06-7.24; sensitivity, 47.4%; specificity, 78.1%; positive predictive value, 4.4%; negative predictive value, 98.6%) for this outcome. Thirteen (.3%) patients had myocardial infarction according to our predetermined definition, and the maximum HR greater than 110 beats/min had an OR of 1.72 (95% CI, 0.47-6.27). Postoperative tachycardia within the first 4 days of surgery should not be dismissed as a postoperative variation in HR, but may precede clinically significant adverse outcomes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Clinical utility of new bleeding criteria: a prospective study of evaluation for the Bleeding Academic Research Consortium definition of bleeding in patients undergoing percutaneous coronary intervention.

PubMed

Choi, Jae-Hyuk; Seo, Jeong-Min; Lee, Dong Hyun; Park, Kyungil; Kim, Young-Dae

2015-04-01

The aim of this study was to evaluate the clinical utility of the new bleeding criteria, proposed by the Bleeding Academic Research Consortium (BARC), compared with the old criteria for determining the action of physicians in contact with bleeding events, after percutaneous coronary intervention (PCI). The BARC criteria were independently associated with an increased risk of 1-year mortality after PCI, and provided a predictive value, in regard to 1-year mortality. The standardized bleeding definitions will be expected to help the physician to correctly analyze the bleeding events, to select an optimal treatment, and to objectively compare the results of multiple trials and registries. All the patients undergoing PCI from June to September 2012 were prospectively enrolled. Patients who experienced a bleeding event were further classified, based on three different bleeding severity criteria: BARC, Thrombolysis In Myocardial Infarction (TIMI), and Global Use of Strategies To Open coronary arteries (GUSTO). The primary outcome was the occurrence of bleeding events requiring interruption of antiplatelet therapy (IAT) by physicians. A total of 376 consecutive patients were included in this study. Total bleeding events occurred in 46 patients (12.2%). BARC type ≥2 bleeding occurred in 30 patients (8.0%); however, TIMI major or minor bleeding, and GUSTO moderate or severe bleeding occurred in 6 (1.6%) and 11 patients (2.9%), respectively. Of the 46 patients, 28 (60.9% of patients) required IAT. On receiver-operating characteristic curve analysis, bleeding defined BARC type ≥2 effectively predicted IAT, with a sensitivity of 89.3%, and a specificity of 98.5% (p<0.001), compared with TIMI (sensitivity, 21.4%; specificity, 100%; p<0.001), and GUSTO (sensitivity, 39.3%; specificity, 100%; p<0.001). Compared with TIMI and GUSTO, the BARC definition may be a more useful tool for the detection of bleeding with clinical relevance, for patients undergoing PCI. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Clinical trials with multiple endpoints can establish a correlation, but not (yet) causality, between dietary supplementation with omega-3 fatty acids and keratoconjunctivitis sicca.

PubMed

Mendoza, Roger Lee

2018-06-13

We review clinical evidence of therapeutic efficacy and effectiveness of omega-3 fatty acids (omega-3s) in keratoconjunctivitis sicca, colloquially known as dry eye disease. In doing so, we identify relevant literature to address the following questions: (1) What definitive guidance can clinical evidence offer eye physicians and their patients? (2) What aspects of omega-3 supplementation lack definitive evidence, and how might economic assessments help? A targeted and systematic search strategy based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was designed in this study for refereed clinical trials of omega-3s in dry eye treatment. Four key databases were accessed. Records were filtered through a three-step process using predetermined inclusion criteria. Data was extracted for experimental design, sample population characteristics, content of test and control groups, symptoms and associated opthalmologic conditions, diagnostic measures, patient health outcomes, adverse events, and model time horizon. A total of 219 records were initially identified, of which 21 prospective clinical trials, with a total of 2,973 participants, were admitted for review. Clinical evidence indicates that daily oral supplementation with omega-3s statistically correlates with dry eye treatment in the general symptomatic population as well as induced sub-populations. Reported adverse events are minimal. These trials nonetheless exhibit considerable heterogeneity in clinical endpoints, particularly as a result of the multi-factorial character of dry eye as well as continuous advances in scientific knowledge and technology. Their findings and recommendations appear to be of limited external validity. And causal inferences are needed, but difficult to establish. These have encouraged and sustained wide variations in ophthalmologic practice and normative decision-making. Comparability of omega-3 therapeutic efficacy and effectiveness remains a major challenge in dry eye disease management. Notwithstanding its multi-factorial character, addressing prevailing methodological and empirical issues in clinical trials will help reduce knowledge gaps and normative choices among eye physicians and patients alike. In this regard, pharmacoeconomics offers a useful and robust toolset through which analysis of cost-minimization, cost-effectiveness, and cost-utility as well as meta-analysis can be comparatively pursued. Blending measures of costs and outcomes puts in perspective the heterogeneity of clinical endpoints in keratoconjunctivitis sicca.

Very-high-risk localized prostate cancer: definition and outcomes.

PubMed

Sundi, D; Wang, V M; Pierorazio, P M; Han, M; Bivalacqua, T J; Ball, M W; Antonarakis, E S; Partin, A W; Schaeffer, E M; Ross, A E

2014-03-01

Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.

A literature review on self-care of chronic illness: definition, assessment and related outcomes.

PubMed

Ausili, Davide; Masotto, Matteo; Dall'Ora, Chiara; Salvini, Lorena; Di Mauro, Stefania

2014-01-01

Chronic illnesses care represents a challenging issue for people well-being and future health systems' sustainability. Promotion of self-care is considered a key point for chronically ill patients' care. The aim of this literature was to explore: how self-care of chronic illness has been theoretically defined; how self-care can be assessed in clinical and research settings; what associations exist between self-care and health outcomes of chronically ill patients. A wide range of definitions and terminologies related to self-care of chronic illness has been found in the literature. Although some common elements useful to explain the concept of self-care have been identified, the physical, cognitive, emotional and social processes underlying self-care remain controversial and poorly defined. Valid and reliable disease-specific assessment tools have been developed and used in a growing number of studies; however, the lack of utilization of standardized instruments in clinical practice has been referred by many authors. Significant correlations between self-care of chronic illness and outcome measures e.g. general health status, quality of life and healthcare costs, are reported by a limited number of studies. Supporting patient self-care is recognized as a crucial factor in chronic illness care. A deeper analysis of variables and processes influencing self-care could help for a full description of the phenomenon. A systematic evaluation of self-care in health professionals' everyday clinical practice is strongly recommended. The development of general non-disease-specific assessment tools could facilitate the evaluation of complex patients, especially those with multiple co-morbidities. Although self-care has been recognized as a vital intermediate outcome, further large-scale studies clarifying the association between self-care and patients' and health systems' outcomes are needed.

Targeting Functional Decline: Results from the Alzheimer’s Disease Multiple Intervention Trial

PubMed Central

Callahan, Christopher M.; Boustani, Malaz A.; Schmid, Arlene A.; LaMantia, Michael A.; Austrom, Mary G.; Miller, Douglas K.; Gao, Sujuan; Ferguson, Denisha Y.; Lane, Kathleen A.; Hendrie, Hugh C.

2017-01-01

Background Alzheimer’s disease (AD) results in progressive functional decline leading to loss of independence Objective To determine whether collaborative care plus two years of home-based occupational therapy delays functional decline Design Randomized controlled clinical trial Setting Urban public health system Patients 180 community-dwelling subjects who were diagnosed with AD and their informal caregivers Interventions All subjects received collaborative care for dementia. Intervention patients also received in-home occupational therapy delivered in 24 sessions over 2 years. Measurements The primary outcome measures was the Alzheimer’s Disease Cooperative Studies Group Activities of Daily Living Scale (ADCS ADL); performance based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM) Results At baseline, there were no significant between group differences in clinical characteristics; the mean MMSE for both groups was 19 (SD=7). The intervention group received a median of 18 home visits from the study occupational therapists. Both groups declined in ADCS ADL scores over 24 months. At the primary endpoint of 24 months, there were no between group differences in ADCS ADL scores (mean difference 2.34, 95% CI −5.27, 9.96). We were also unable to definitively demonstrate between-group differences in the mean SPPB or SPSM. Limitations The results of this trial are indeterminate and do not rule out potentially clinically important effects of the intervention. Conclusions We were unable to definitively demonstrate whether the addition of two years of in-home occupational therapy to a collaborative care management model slows the rate of functional decline among persons with AD. This trial underscores the burden undertaken by family caregivers as they provide care for persons with AD and the difficulty in slowing functional decline. PMID:27893087

Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery.

PubMed

Zappitelli, Michael; Greenberg, Jason H; Coca, Steven G; Krawczeski, Catherine D; Li, Simon; Thiessen-Philbrook, Heather R; Bennett, Michael R; Devarajan, Prasad; Parikh, Chirag R

2015-06-01

Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use. Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.

Association of Definition of Acute Kidney Injury by Cystatin C Rise With Biomarkers and Clinical Outcomes in Children Undergoing Cardiac Surgery

PubMed Central

Zappitelli, Michael; Greenberg, Jason H.; Coca, Steven G.; Krawczeski, Catherine D.; Li, Simon; Thiessen-Philbrook, Heather R.; Bennett, Michael R.; Devarajan, Prasad; Parikh, Chirag R.

2015-01-01

IMPORTANCE Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. OBJECTIVE To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. EXPOSURES For biomarker vs clinical AKI associations, the exposures were first postoperative (0–6 hours after surgery) urine interleukin 18, neutrophil gelatinase – associated lipocalin, kidney injury molecule 1, and liver fatty acid–binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). MAIN OUTCOMES AND MEASURES Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. RESULTS The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55–73.93) and 6.93 (95% CI, 1.88–25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76–15.76) and 2.04 (95% CI, 0.94–4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase–associated lipocalin and liver fatty acid–binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use. CONCLUSIONS AND RELEVANCE Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies. PMID:25844892

Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital.

PubMed

Teh, Benjamin W; Worth, Leon J; Harrison, Simon J; Thursky, Karin A; Slavin, Monica A

2015-07-01

Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.

A Summary of the Biological Basis of Frailty.

PubMed

Fielding, Roger A

2015-01-01

Frailty has been defined as a geriatric syndrome that is characterized by a reduction in the physiological reserve required for an individual to respond to endogenous and exogenous stressors. Using a discrete definition of frailty that includes sedentariness, involuntary weight loss, fatigue, poor muscle strength, and slow gait speed, 'frailty' has been associated with increased disability, postsurgical complications, and increased mortality. Despite the strong associations between frailty and subsequent poor outcomes, limited attention to this common geriatric condition has been paid in clinical settings. A more fundamental basic understanding of the biological factors that contribute to the frailty phenotype has begun to emerge. Multiple underlying biological factors such as dysregulation of inflammatory processes, genomic instability, oxidative stress, mitochondrial dysfunction, and cellular senescence appear to contribute to the clinical presentation of frailty. This chapter summarizes the papers presented on the biological basis of frailty from the 83rd Nestlé Nutrition Institute Workshop on 'Frailty, Pathophysiology, Phenotype and Patient Care' held in Barcelona, Spain, in March 2014. © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel.

A generalized concept of power helped to choose optimal endpoints in clinical trials.

PubMed

Borm, George F; van der Wilt, Gert J; Kremer, Jan A M; Zielhuis, Gerhard A

2007-04-01

A clinical trial may have multiple objectives. Sometimes the results for several parameters may need to be significant or meet certain other criteria. In such cases, it is important to evaluate the probability that all these objectives will be met, rather than the probability that each will be met. The purpose of this article is to introduce a definition of power that is tailored to handle this situation and that is helpful for the design of such trials. We introduce a generalized concept of power. It can handle complex situations, for example, in which there is a logical combination of partial objectives. These may be formulated not only in terms of statistical tests and of confidence intervals, but also in nonstatistical terms, such as "selecting the optimal by dose." The power of a trial was calculated for various objectives and combinations of objectives. The generalized concept of power may lead to power calculations that closely match the objectives of the trial and contribute to choosing more efficient endpoints and designs.

[Systemic learning planification for medical students during oncology clinical rotation].

PubMed

Gonçalves, Anthony; Viens, Patrice; Gilabert, Marine; Turrini, Olivier; Lambaudie, Eric; Prebet, Thomas; Farnault, Bertrand; Eisinger, François; Gorincour, Guillaume; Bertucci, François

2011-12-01

The expected increase in cancer incidence emphasizes the need for specific training in this area, including either family physician or specialized oncologists. In France, the fourth to sixth years of medical teaching include both theoretical classes at the university and daily actual practice at the hospital. Thus, clinical rotations are thought to play a major role in the training of medical students and also largely participate to the choice of the student of his/her final specialty. Pedagogic quality of these rotations is dependent on multiple parameters, including a rigorous planification of the expected learning. Here, we reported a systemic planification of learning activities for medical students during an oncology rotation at the Paoli-Calmettes Institute in Marseille, France, a regional comprehensive cancer center. This planification includes an evaluation of learning requirements, definition of learning objectives, selection of learning methods and choice of methods of assessment of the students' achievement of these objectives as well as the learning activity itself.

Phyllodes tumours of the breast: a consensus review

PubMed Central

Tan, Benjamin Y; Acs, Geza; Apple, Sophia K; Badve, Sunil; Bleiweiss, Ira J; Brogi, Edi; Calvo, José P; Dabbs, David J; Ellis, Ian O; Eusebi, Vincenzo; Farshid, Gelareh; Fox, Stephen B; Ichihara, Shu; Lakhani, Sunil R; Rakha, Emad A; Reis-Filho, Jorge S; Richardson, Andrea L; Sahin, Aysegul; Schmitt, Fernando C; Schnitt, Stuart J; Siziopikou, Kalliopi P; Soares, Fernando A; Tse, Gary M; Vincent-Salomon, Anne; Tan, Puay Hoon

2016-01-01

Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours. PMID:26768026

Expanding a First-Order Logic Mitigation Framework to Handle Multimorbid Patient Preferences

PubMed Central

Michalowski, Martin; Wilk, Szymon; Rosu, Daniela; Kezadri, Mounira; Michalowski, Wojtek; Carrier, Marc

2015-01-01

The increasing prevalence of multimorbidity is a challenge for physicians who have to manage a constantly growing number of patients with simultaneous diseases. Adding to this challenge is the need to incorporate patient preferences as key components of the care process, thanks in part to the emergence of personalized and participatory medicine. In our previous work we proposed a framework employing first order logic to represent clinical practice guidelines (CPGs) and to mitigate possible adverse interactions when concurrently applying multiple CPGs to a multimorbid patient. In this paper, we describe extensions to our methodological framework that (1) broaden our definition of revision operators to support required and desired types of revisions defined in secondary knowledge sources, and (2) expand the mitigation algorithm to apply revisions based on their type. We illustrate the capabilities of the expanded framework using a clinical case study of a multimorbid patient with stable cardiac artery disease who suffers a sudden onset of deep vein thrombosis. PMID:26958226

ASPEN-AND-ESPEN: A postacute-care comparison of the basic definition of malnutrition from the American Society of Parenteral and Enteral Nutrition and Academy of Nutrition and Dietetics with the European Society for Clinical Nutrition and Metabolism definition.

PubMed

Sánchez-Rodríguez, Dolores; Marco, Ester; Ronquillo-Moreno, Natalia; Maciel-Bravo, Liev; Gonzales-Carhuancho, Abel; Duran, Xavier; Guillén-Solà, Anna; Vázquez-Ibar, Olga; Escalada, Ferran; Muniesa, Josep M

2018-01-25

The aim of this study was to assess the prevalence of malnutrition by applying the ASPEN/AND definition and the ESPEN consensus definition in a postacute-care population, and secondly, to determine the metrological properties of the set of six clinical characteristics that constitute the ASPEN/AND basic diagnosis, compared to the ESPEN consensus, based mostly on objective anthropometric measurements. Prospective study of 84 consecutive deconditioned older inpatients (85.4 ± 6.2; 59.5% women) admitted for rehabilitation in postacute care. ASPEN/AND diagnosis of malnutrition was considered in presence of at least two of the following: low energy intake, fluid accumulation, diminished handgrip strength, and loss of weight, muscle mass, or subcutaneous fat. Sensitivity, specificity, positive and negative predictive values, accuracy, likelihood ratios, and kappa statistics were calculated for ASPEN/AND criteria and compared with ESPEN consensus. The prevalence of malnutrition by ASPEN/AND criteria was 63.1% and by ESPEN consensus, 20.2%; both diagnoses were associated with significantly longer length of stay, but the ESPEN definition was significantly associated with poorer functional outcomes after the rehabilitation program. Compared to ESPEN consensus, ASPEN/AND diagnosis showed fair validity (sensitivity = 94.1%; specificity = 44.8%); kappa statistic was 2.217. Applying the ASPEN/AND definition obtained a higher prevalence of malnutrition in a postacute-care population than was identified by the ESPEN definition. ASPEN/AND criteria had fair validity and agreement compared with the ESPEN definition. A simple, evidence-based, unified malnutrition definition might improve geriatric care. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

PubMed

Ruperto, Nicolino; Pistorio, Angela; Ravelli, Angelo; Rider, Lisa G; Pilkington, Clarissa; Oliveira, Sheila; Wulffraat, Nico; Espada, Graciela; Garay, Stella; Cuttica, Ruben; Hofer, Michael; Quartier, Pierre; Melo-Gomes, Jose; Reed, Ann M; Wierzbowska, Malgorzata; Feldman, Brian M; Harjacek, Miroslav; Huppertz, Hans-Iko; Nielsen, Susan; Flato, Berit; Lahdenne, Pekka; Michels, Harmut; Murray, Kevin J; Punaro, Lynn; Rennebohm, Robert; Russo, Ricardo; Balogh, Zsolt; Rooney, Madeleine; Pachman, Lauren M; Wallace, Carol; Hashkes, Philip; Lovell, Daniel J; Giannini, Edward H; Gare, Boel Andersson; Martini, Alberto

2010-11-01

To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM. Copyright © 2010 by the American College of Rheumatology.

An evaluation of the usefulness of consensus definitions of sarcopenia in older men: results from the observational Osteoporotic Fractures in Men (MrOS) cohort study

PubMed Central

Cawthon, Peggy M; Blackwell, Terri L; Cauley, Jane; Kado, Deborah M; Barrett-Connor, Elizabeth; Lee, Christine G; Hoffman, Andrew R; Nevitt, Michael M; Stefanick, Marcia L; Lane, Nancy E; Ensrud, Kristine E; Cummings, Steven R; Orwoll, Eric S

2016-01-01

Background Recently, several consensus definitions for sarcopenia have been developed. Objective To evaluate the associations and discriminative ability of definitions of sarcopenia against clinical outcomes. Design Osteoporotic Fractures in Men study Setting Six clinical centers Participants 5,934 community-dwelling men aged ≥65 yrs Measurements Sarcopenia definitions evaluated were: International Working Group (IWG), European Working Group for Sarcopenia in Older Persons (EWGSOP), Foundation for the NIH (FNIH) Sarcopenia, Baumgartner, and Newman. Recurrent falls were defined as ≥2 self-reported falls in the year after baseline (N=694, 11.9%). Incident hip fractures (N=207, 3.5 %) and deaths (N=2003, 34.1%) were confirmed by central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and again 4.6 years later. Logistic regression or proportional hazards models estimated associations between sarcopenia and falls, hip fractures or death. The discriminative ability of the sarcopenia definitions (compared to referent models) for these outcomes was evaluated with areas under the receiver operator curve (AUCs) or C-statistics. Referent models included age alone for falls, function limitations and mortality, and age and BMD for hip fractures. Results The association between sarcopenia by the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with increased mortality risk. However, none of the definitions materially changed discrimination based on AUC and C-statistic when compared to referent models (change ≤1% in all models). Conclusions Sarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men. PMID:26502831

Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data.

PubMed

Rhoads, Stephanie Golubic; Hendricks, Heather M; Frazier-Bowers, Sylvia A

2013-08-01

Proper diagnosis and management of eruption disturbances remains challenging but is critical to a functional occlusion. The objective of this study was to establish definitive criteria to differentiate and diagnose eruption disorders, specifically primary failure of eruption (PFE) and ankylosis. Sixty-four affected persons were placed into 3 cohorts: PFE diagnosed through confirmed PTH1R mutation (n = 11), PFE diagnosed based on clinical criteria (n = 47), and ankylosis diagnosed based on clinical criteria (n = 6). These groups were assessed to identify clinical features that differentiate PFE and ankylosis. Ninety-three percent of the subjects in the genetic and clinical PFE cohorts combined (n = 58) and 100% in the genetic PFE cohort had at least 1 infraoccluded first permanent molar. Additionally, a novel functional PTH1R mutation, 1092delG, was identified and linked to PFE in the deciduous dentition. An infraoccluded, supracrestal first molar is a hallmark of PFE, often involving both arches in the permanent or deciduous dentition, and with unilateral or bilateral affection, infraoccluded second premolar or second molar, and multiple affected adjacent teeth. Our results further suggest that PFE and ankylosis might be clinically indistinguishable without knowledge of prior trauma, treatment history, genetic information, or obliteration of the periodontal ligament space. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

The operator algebra approach to quantum groups

PubMed Central

Kustermans, Johan; Vaes, Stefaan

2000-01-01

A relatively simple definition of a locally compact quantum group in the C*-algebra setting will be explained as it was recently obtained by the authors. At the same time, we put this definition in the historical and mathematical context of locally compact groups, compact quantum groups, Kac algebras, multiplicative unitaries, and duality theory. PMID:10639116

Preliminary definition of improvement in juvenile arthritis.

PubMed

Giannini, E H; Ruperto, N; Ravelli, A; Lovell, D J; Felson, D T; Martini, A

1997-07-01

To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.

Would a new definition and classification of nocturia and nocturnal polyuria improve our management of patients? ICI-RS 2014.

PubMed

Bosch, J L H Ruud; Everaert, Karel; Weiss, Jeffrey P; Hashim, Hashim; Rahnama'i, M Sajjad; Goessaert, An-Sofie; Aizen, Joshua

2016-02-01

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place September 22-24, 2014 in Bristol, UK. The report is organized into sections pertaining to the main topic of discussion focussing on the question as to whether a new definition and classification of nocturia and nocturnal polyuria would improve the outcome of management in our patients. First, discussions identified theoretical and practical shortcomings of current definitions. Secondly, the utility of several nocturnal polyuria definitions was tested in a real life population in relation to the symptom nocturia, in order to display weaknesses of these definitions. Thirdly, we explored in a clinical population the utility of bladder diary based parameters by asking the question: when nocturia improves, which of these parameters improve most? Based on the above explorations the Think Tank summarized elements of the current definitions that need reconsideration and suggests proposals for further research to reach more practical and more clinically meaningful definitions. © 2015 Wiley Periodicals, Inc.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

The relationship of three common definitions of the metabolic syndrome with sub-clinical carotid atherosclerosis.

PubMed

Paras, Erica; Mancini, G B John; Lear, Scott A

2008-05-01

Presence of the metabolic syndrome (MetS) increases a patient's risk for future cardiovascular disease. However, there is no consensus as to which of the proposed definitions should be used. Therefore, using carotid atherosclerotic burden as an index of cumulative effects of atherosclerotic risk factors, we assessed the association of the three commonly used MetS definitions with sub-clinical atherosclerosis in a primary prevention population and determined if this association was independent of the component risk factors. A multi-ethnic cohort of 796 men and women without cardiovascular disease was assessed for demographics, risk factors, properties of the carotid arteries using ultrasound and presence or absence of MetS based on each of the World Health Organization (WHO), the National Cholesterol Education Program Expert Panel (NCEP) and the International Diabetes Federation (IDF) definitions. Using any definition, 29% of the cohort had MetS. After adjusting for age, gender, ethnicity and smoking status, participants with MetS had greater intima-media thickening and total area (intima-media area and focal lesion area combined) than participants without MetS. Only participants meeting the WHO MetS criteria had a greater prevalence of focal lesions. After further adjustment for the individual risk factor components of each MetS definition separately, none of MetS definitions was associated with any of the carotid artery measures. All three MetS definitions were associated with measures of sub-clinical carotid atherosclerosis and these associations were entirely mediated through the risk factor components of MetS.

Consensus Based Definition of Growth Restriction in the Newborn.

PubMed

Beune, Irene M; Bloomfield, Frank H; Ganzevoort, Wessel; Embleton, Nicholas D; Rozance, Paul J; van Wassenaer-Leemhuis, Aleid G; Wynia, Klaske; Gordijn, Sanne J

2018-05-01

To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard. An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm. In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight <10th percentile; head circumference <10th percentile; length <10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information. Consensus was reached on a definition for growth restriction in the newborn. This definition recognizes that infants with birth weights <10th percentile may not be growth restricted and that infants with birth weights >10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

[Study on differences between pharmacokinetics and chromatopharmacodynamics for Chinese materia medica formulae].

PubMed

He, Fuyuan; Deng, Kaiwen; Zou, Huan; Qiu, Yun; Chen, Feng; Zhou, Honghao

2011-01-01

To study on the differences between chromatopharmacokinetics (pharmacokinetics with fingerprint chromatography) and chromatopharmacodynamics (pharmacodynamics with fingerprint chromatography) of Chinese materia medica formulae to answer the question whether the pharmacokinetic parameters of multiple composites can be utilized to guide the medication of multiple composites. On the base of established four chromatopharmacology (pharmacology with chromatographic fingerprint), the pharmacokinetics, and pharmacodynamics were analyzed comparably on their mathematical model and parameter definition. On the basis of quantitative pharmacology, the function expressions and total statistical parameters, such as total zero moment, total first moment, total second moment of the pharmacokinetics, and pharmacodynamics were analyzed to the common expressions and elucidated results for single and multiple components in Chinese materia medica formulae. Total quantitative pharmacokinetic, i.e., chromatopharmacokinetic parameter were decided by each component pharmacokinetic parameters, whereas the total quantitative pharmacodynamic, i.e., chromatopharmacodynamic parameter were decided by both of pharmacokinetic and pharmacodynamic parameters of each components. The pharmacokinetic parameters were corresponded to pharmacodynamic parameters with an existing stable effective coefficient when the constitutive ratio of each composite was a constant. The effects of Chinese materia medica were all controlled by pharmacokinetic and pharmacodynamic coefficient. It is a special case that the pharmacokinetic parameter could independently guide the clinical medication for single component whereas the chromatopharmacokinetic parameters are not applied to the multiple drug combination system, and not be used to solve problems of chromatopharmacokinetic of Chinese materia medica formulae.

Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.

PubMed

Cohen, Jeffrey A; Imrey, Peter B; Planchon, Sarah M; Bermel, Robert A; Fisher, Elizabeth; Fox, Robert J; Bar-Or, Amit; Sharp, Susan L; Skaramagas, Thomai T; Jagodnik, Patricia; Karafa, Matt; Morrison, Shannon; Reese Koc, Jane; Gerson, Stanton L; Lazarus, Hillard M

2018-04-01

Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 10 6 MSCs/kg were thawed and administered IV. In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 10 6 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

20 CFR 345.102 - Multiple employer limitation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Multiple employer limitation. 345.102 Section 345.102 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT EMPLOYERS' CONTRIBUTIONS AND CONTRIBUTION REPORTS General Provisions and Definitions § 345.102...

Dear Verity: Why Are All the Dictionaries Wrong?

ERIC Educational Resources Information Center

Dempsey, Deirdre; Marshall, John

2001-01-01

An education major enrolled in a mathematics education course ponders confusing definitions of "multiplication" functions in dictionaries and in a handout on Euclid. This student teacher wants to teach elementary students what multiplication really is, not just impart an algorithmic skill. (MLH)

Clinical Research Informatics: Challenges, Opportunities and Definition for an Emerging Domain

PubMed Central

Embi, Peter J.; Payne, Philip R.O.

2009-01-01

Objectives Clinical Research Informatics, an emerging sub-domain of Biomedical Informatics, is currently not well defined. A formal description of CRI including major challenges and opportunities is needed to direct progress in the field. Design Given the early stage of CRI knowledge and activity, we engaged in a series of qualitative studies with key stakeholders and opinion leaders to determine the range of challenges and opportunities facing CRI. These phases employed complimentary methods to triangulate upon our findings. Measurements Study phases included: 1) a group interview with key stakeholders, 2) an email follow-up survey with a larger group of self-identified CRI professionals, and 3) validation of our results via electronic peer-debriefing and member-checking with a group of CRI-related opinion leaders. Data were collected, transcribed, and organized for formal, independent content analyses by experienced qualitative investigators, followed by an iterative process to identify emergent categorizations and thematic descriptions of the data. Results We identified a range of challenges and opportunities facing the CRI domain. These included 13 distinct themes spanning academic, practical, and organizational aspects of CRI. These findings also informed the development of a formal definition of CRI and supported further representations that illustrate areas of emphasis critical to advancing the domain. Conclusions CRI has emerged as a distinct discipline that faces multiple challenges and opportunities. The findings presented summarize those challenges and opportunities and provide a framework that should help inform next steps to advance this important new discipline. PMID:19261934

A pragmatic definition of therapeutic synergy suitable for clinically relevant in vitro multicompound analyses.

PubMed

Kashif, Muhammad; Andersson, Claes; Åberg, Magnus; Nygren, Peter; Sjöblom, Tobias; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

2014-07-01

For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. ©2014 American Association for Cancer Research.

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

PubMed

Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

2015-09-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis, and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency.

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

PubMed Central

Gilbert, Peter B.; Gabriel, Erin E.; Huang, Ying; Chan, Ivan S.F.

2015-01-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis, and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency. PMID:26722639

Considerations concerning the definition of sarcopenia

USDA-ARS?s Scientific Manuscript database

In this commentary, we describe the sarcopenia spectrum that results in frailty and consider the impact of several components of the frailty definition on its global prevalence. We review proposed operational definitions of sarcopenia the extent to which they have been shown to predict hard clinical...

Remission in systemic lupus erythematosus: durable remission is rare.

PubMed

Wilhelm, Theresa R; Magder, Laurence S; Petri, Michelle

2017-03-01

Remission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission. We applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT. 2307 patients entered the cohort from 1987 to 2014 and were seen at least quarterly. Patients not in remission at cohort entry were followed prospectively. We used the Kaplan-Meier approach to estimate the time to remission and the time from remission to relapse. Cox regression was used to identify baseline factors associated with time to remission, adjusting for baseline disease activity and baseline treatment. The median time to remission was 8.7, 11.0, 1.8 and 3.1 years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment was the major predictor of a longer time to remission, followed by high baseline activity. The median duration of remission for all definitions was 3 months. African-American ethnicity, baseline low C3 and baseline haematological activity were associated with longer time to remission for all definitions. Baseline anti-dsDNA and baseline low C4 were associated with longer time to Complete Remission and Complete ROT. Baseline low C4 was also negatively associated with Clinical Remission. Our results provide further insights into the frequency and duration of remission in SLE and call attention to the major role of baseline activity and baseline treatment in predicting remission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

PubMed

Garcia-Garcia, Hector M; McFadden, Eugène P; Farb, Andrew; Mehran, Roxana; Stone, Gregg W; Spertus, John; Onuma, Yoshinobu; Morel, Marie-Angèle; van Es, Gerrit-Anne; Zuckerman, Bram; Fearon, William F; Taggart, David; Kappetein, Arie-Pieter; Krucoff, Mitchell W; Vranckx, Pascal; Windecker, Stephan; Cutlip, Donald; Serruys, Patrick W

2018-06-12

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices. © 2018 American Heart Association, Inc., and European Society of Cardiology.

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes

PubMed Central

Makris, Konstantinos; Spanou, Loukia

2016-01-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI. PMID:28303073

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

PubMed

Makris, Konstantinos; Spanou, Loukia

2016-05-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

[Damage control in trauma patients with hemodynamic instability].

PubMed

Müller, Thorben; Doll, Dietrich; Kliebe, Frank; Ruchholtz, Steffen; Kühne, Christian

2010-10-01

The term "Damage-control" is borrowed from naval terminology. It means the initial control of a damaged ship. Because of the lethal triad in multiple injured patients the classical concept of definitive surgically therapy in the acute phase of the injury has a high rate of complications such as exsanguination, sepsis, heart failure and multiple organ failure. The core idea of the damage control concept was to minimize the additional trauma by surgical operations in these critical patients in the first phase. This means temporary control of a hemorrhage and measures for stopping abdominal contamination. After 24 - 48 hours in the intensive care unit and correction of physiological disturbances further interventions are performed for definitively treatment of the injuries. Summarized, the damage control strategy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation after hemodynamic stabilisation of the patient. © Georg Thieme Verlag Stuttgart · New York.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

PubMed

Lansky, Alexandra J; Messé, Steven R; Brickman, Adam M; Dwyer, Michael; Bart van der Worp, H; Lazar, Ronald M; Pietras, Cody G; Abrams, Kevin J; McFadden, Eugene; Petersen, Nils H; Browndyke, Jeffrey; Prendergast, Bernard; Ng, Vivian G; Cutlip, Donald E; Kapadia, Samir; Krucoff, Mitchell W; Linke, Axel; Scala Moy, Claudia; Schofer, Joachim; van Es, Gerrit-Anne; Virmani, Renu; Popma, Jeffrey; Parides, Michael K; Kodali, Susheel; Bilello, Michel; Zivadinov, Robert; Akar, Joseph; Furie, Karen L; Gress, Daryl; Voros, Szilard; Moses, Jeffrey; Greer, David; Forrest, John K; Holmes, David; Kappetein, Arie P; Mack, Michael; Baumbach, Andreas

2018-05-14

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Communication Optimal Parallel Multiplication of Sparse Random Matrices

DTIC Science & Technology

2013-02-21

Definition 2.1), and (2) the algorithm is sparsity- independent, where the computation is statically partitioned to processors independent of the sparsity...struc- ture of the input matrices (see Definition 2.5). The second assumption applies to nearly all existing al- gorithms for general sparse matrix-matrix...where A and B are n× n ER(d) matrices: Definition 2.1 An ER(d) matrix is an adjacency matrix of an Erdős-Rényi graph with parameters n and d/n. That

New EAACI definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

PubMed

Karatzas, Kostas; Katsifarakis, Nikos; Riga, Marina; Werchan, Barbora; Werchan, Matthias; Berger, Uwe; Pfaar, Oliver; Bergmann, Karl-Christian

2018-05-23

The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergens exposure time-periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. Data coming from four Pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014 - 2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hayfever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Bancaud and Talairach view on the epileptogenic zone: a working hypothesis.

PubMed

Kahane, Philippe; Landré, Elisabeth; Minotti, Lorella; Francione, Stafano; Ryvlin, Philippe

2006-08-01

The definition of the epileptogenic zone, as proposed by Talairach and Bancaud, is an ictal electro-clinical definition based on the results of stereotactic intracerebral EEG (SEEG) recordings. It takes into account not only the anatomical location of the "site of the beginning and of the primary organization" of the epileptic discharge, but also how this discharge gives rise to the accompanying clinical symptoms. This definition is different from the North American view since, for the French authors, the epileptogenic zone is not synonymous with what can be called the "what-to-remove area". In fact, it is above all a conceptual definition which emphazises the importance of studying the spatio-temporal dynamics of seizure discharges, and not only their starting point.

Addiction recovery: its definition and conceptual boundaries.

PubMed

White, William L

2007-10-01

The addiction field's failure to achieve consensus on a definition of "recovery" from severe and persistent alcohol and other drug problems undermines clinical research, compromises clinical practice, and muddles the field's communications to service constituents, allied service professionals, the public, and policymakers. This essay discusses 10 questions critical to the achievement of such a definition and offers a working definition of recovery that attempts to meet the criteria of precision, inclusiveness, exclusiveness, measurability, acceptability, and simplicity. The key questions explore who has professional and cultural authority to define recovery, the defining ingredients of recovery, the boundaries (scope and depth) of recovery, and temporal benchmarks of recovery (when recovery begins and ends). The process of defining recovery touches on some of the most controversial issues within the addictions field.

Validation of a surveillance case definition for arthritis.

PubMed

Sacks, Jeffrey J; Harrold, Leslie R; Helmick, Charles G; Gurwitz, Jerry H; Emani, Srinivas; Yood, Robert A

2005-02-01

To assess whether self-reports of chronic joint symptoms or doctor-diagnosed arthritis can validly identify persons with clinically verifiable arthritis. The Behavioral Risk Factor Surveillance System (BRFSS), a telephone health survey, defines a case of arthritis as a self-report of chronic joint symptoms (CJS) and/or doctor-diagnosed arthritis (DDx). A sample of health plan enrollees aged 45-64 years and >/= 65 years with upcoming annual physical examinations were surveyed by telephone using the 2002 BRFSS CJS and DDx questions. Based on responses (CJS+, DDx-; CJS-, DDx+; CJS+, DDx+; CJS-, DDx-), respondents were recruited to undergo a standardized clinical history and physical examination for arthritis (the gold standard for clinical validation). Weighted sensitivities and specificities of the case definition were calculated to adjust for sampling. Of 2180 persons completing the telephone questionnaire, 389 were examined; of these, 258 met the case definition and 131 did not. For those examined and aged 45 to 64 years (n = 179), 96 persons had arthritis confirmed, of whom 76 met the case definition. Among those examined and aged >/= 65 (n = 210), 150 had arthritis confirmed, of whom 124 met the case definition. Among those without clinical arthritis, 45 of 83 of those aged 45 to 64 years and 40 of 60 of those aged >/= 65 did not meet the case definition. For those aged 45 to 64 years, the weighted sensitivity of the case definition in this sample was 77.4% and the weighted specificity was 58.8%; for those aged >/= 65, the sensitivity was 83.6% and specificity 70.6%. CJS+ had higher sensitivity and lower specificity than DDx+ in the younger age group; CJS+ and DDx+ behaved more comparably in the older age group. The case definition based on self-reported CJS and/or DDx appeared to be sensitive in identifying arthritis, but specificity was lower than desirable for those under age 65 years. Better methods of ascertaining arthritis by self-report are needed. Until then, a change in the surveillance case definition for arthritis appears warranted.

Defining post-sternotomy mediastinitis for clinical evidence-based studies.

PubMed

van Wingerden, Jan J; de Mol, Bas A J M; van der Horst, Chantal M A M

2016-05-01

Considerable advances have already been made in the treatment of deep thoracic wound infections following a median sternotomy for cardiac surgery. Further improvement in diagnosis, treatment, and outcome will require a targeted approach by multidisciplinary teams. Clear communication and synergy between the various clinical and supportive disciplines would assist in removing the last barriers to standardized evidence-based studies and the development of improved evidence-based guidelines. An extensive literature search without language restrictions was carried out on PubMed (Medline), EMBASE, and Web of Science, covering the period 1988 to week 16, 2014, and a manual search of the reference lists was performed regarding all possible definitions and classifications of post-sternotomy mediastinitis. Two hundred and eighteen papers describing post-sternotomy infections in a multitude of terms were identified, and the strengths and weaknesses of the most popular definitions and terms relating specifically to post-sternotomy infections were examined. This study revealed that clinicians use a multitude of terms to describe post-sternotomy infections without defining the condition under treatment. Occasionally, older epidemiological (surveillance) definitions were used. It also shows that supportive disciplines have their own definitions, or interpretations of existing definitions, to describe these infections. The outcome of this study is that clinicians have adopted no single definition, which is essential for further improvement for evidence-based studies. We suggest that it is possible to adopt a single term for thoracic infection after a sternotomy (and only sternotomy), and propose a clinical definition for this purpose. © The Author(s) 2016.

Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

PubMed

Pozzilli, C; Prosperini, L; Sbardella, E; De Giglio, L; Onesti, E; Tomassini, V

2005-12-01

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

Defining and assessing professional competence.

PubMed

Epstein, Ronald M; Hundert, Edward M

2002-01-09

Current assessment formats for physicians and trainees reliably test core knowledge and basic skills. However, they may underemphasize some important domains of professional medical practice, including interpersonal skills, lifelong learning, professionalism, and integration of core knowledge into clinical practice. To propose a definition of professional competence, to review current means for assessing it, and to suggest new approaches to assessment. We searched the MEDLINE database from 1966 to 2001 and reference lists of relevant articles for English-language studies of reliability or validity of measures of competence of physicians, medical students, and residents. We excluded articles of a purely descriptive nature, duplicate reports, reviews, and opinions and position statements, which yielded 195 relevant citations. Data were abstracted by 1 of us (R.M.E.). Quality criteria for inclusion were broad, given the heterogeneity of interventions, complexity of outcome measures, and paucity of randomized or longitudinal study designs. We generated an inclusive definition of competence: the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, values, and reflection in daily practice for the benefit of the individual and the community being served. Aside from protecting the public and limiting access to advanced training, assessments should foster habits of learning and self-reflection and drive institutional change. Subjective, multiple-choice, and standardized patient assessments, although reliable, underemphasize important domains of professional competence: integration of knowledge and skills, context of care, information management, teamwork, health systems, and patient-physician relationships. Few assessments observe trainees in real-life situations, incorporate the perspectives of peers and patients, or use measures that predict clinical outcomes. In addition to assessments of basic skills, new formats that assess clinical reasoning, expert judgment, management of ambiguity, professionalism, time management, learning strategies, and teamwork promise a multidimensional assessment while maintaining adequate reliability and validity. Institutional support, reflection, and mentoring must accompany the development of assessment programs.

American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials.

PubMed

Felson, David T; Smolen, Josef S; Wells, George; Zhang, Bin; van Tuyl, Lilian H D; Funovits, Julia; Aletaha, Daniel; Allaart, Cornelia F; Bathon, Joan; Bombardieri, Stefano; Brooks, Peter; Brown, Andrew; Matucci-Cerinic, Marco; Choi, Hyon; Combe, Bernard; de Wit, Maarten; Dougados, Maxime; Emery, Paul; Furst, Daniel; Gomez-Reino, Juan; Hawker, Gillian; Keystone, Edward; Khanna, Dinesh; Kirwan, John; Kvien, Tore K; Landewé, Robert; Listing, Joachim; Michaud, Kaleb; Martin-Mola, Emilio; Montie, Pamela; Pincus, Theodore; Richards, Pamela; Siegel, Jeffrey N; Simon, Lee S; Sokka, Tuulikki; Strand, Vibeke; Tugwell, Peter; Tyndall, Alan; van der Heijde, Desirée; Verstappen, Suzan; White, Barbara; Wolfe, Frederick; Zink, Angela; Boers, Maarten

2011-03-01

Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3. We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.

American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials.

PubMed

Felson, David T; Smolen, Josef S; Wells, George; Zhang, Bin; van Tuyl, Lilian H D; Funovits, Julia; Aletaha, Daniel; Allaart, Cornelia F; Bathon, Joan; Bombardieri, Stefano; Brooks, Peter; Brown, Andrew; Matucci-Cerinic, Marco; Choi, Hyon; Combe, Bernard; de Wit, Maarten; Dougados, Maxime; Emery, Paul; Furst, Daniel; Gomez-Reino, Juan; Hawker, Gillian; Keystone, Edward; Khanna, Dinesh; Kirwan, John; Kvien, Tore K; Landewé, Robert; Listing, Joachim; Michaud, Kaleb; Martin-Mola, Emilio; Montie, Pamela; Pincus, Theodore; Richards, Pamela; Siegel, Jeffrey N; Simon, Lee S; Sokka, Tuulikki; Strand, Vibeke; Tugwell, Peter; Tyndall, Alan; van der Heijde, Desirée; Verstappen, Suzan; White, Barbara; Wolfe, Frederick; Zink, Angela; Boers, Maarten

2011-03-01

Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (e.g., tender and swollen joint counts, C-reactive protein [CRP] level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year followup data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (a) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤ 1, or (b) when the score on the Simplified Disease Activity Index is ≤ 3.3. We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial. Copyright © 2011 by the American College of Rheumatology.

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation.

PubMed

Levine, Deborah J; Glanville, Allan R; Aboyoun, Christina; Belperio, John; Benden, Christian; Berry, Gerald J; Hachem, Ramsey; Hayes, Don; Neil, Desley; Reinsmoen, Nancy L; Snyder, Laurie D; Sweet, Stuart; Tyan, Dolly; Verleden, Geert; Westall, Glen; Yusen, Roger D; Zamora, Martin; Zeevi, Adriana

2016-04-01

Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Donepezil improved memory in multiple sclerosis in a randomized clinical trial.

PubMed

Krupp, L B; Christodoulou, C; Melville, P; Scherl, W F; MacAllister, W S; Elkins, L E

2004-11-09

To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Nonlinearity of the forward-backward correlation function in the model with string fusion

NASA Astrophysics Data System (ADS)

Vechernin, Vladimir

2017-12-01

The behavior of the forward-backward correlation functions and the corresponding correlation coefficients between multiplicities and transverse momenta of particles produced in high energy hadronic interactions is analyzed by analytical and MC calculations in the models with and without string fusion. The string fusion is taking into account in simplified form by introducing the lattice in the transverse plane. The results obtained with two alternative definitions of the forward-backward correlation coefficient are compared. It is shown that the nonlinearity of correlation functions increases with the width of observation windows, leading at small string density to a strong dependence of correlation coefficient value on the definition. The results of the modeling enable qualitatively to explain the experimentally observed features in the behavior of the correlation functions between multiplicities and mean transverse momenta at small and large multiplicities.

Management of Skin Cancer in the High-Risk Patient.

PubMed

Behan, James W; Sutton, Adam; Wysong, Ashley

2016-12-01

Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

Advances in understanding behavioral phenotypes in neurogenetic syndromes.

PubMed

Harris, James C

2010-11-15

Syndrome-specific behavior was proposed by Langdon Down in his first clinical descriptions. Research interest followed but waned during the eugenics era when antisocial behavior was attributed to people with intellectual disability (ID) and the US Supreme Court legalized involuntary sterilization. When these claims were refuted and behavioral treatments introduced, their focus on environmental determination minimized the importance of biological research. The modern era began with the recognition that patterned behavior, for example, self-injury in Lesch-Nyhan syndrome and hyperphagia in PWS, was syndrome-specific, and when parent support groups pointed out syndrome-specific behavioral similarities in their children. Syndrome-specific rating scales and methodologies followed to allow behavioral comparisons between syndromes. The focus initially was on specific behaviors but with refinements in neuropsychological tests has expanded to include neurocognitive profiles. Greater clarification in genetic diagnoses has led to mutant mouse behavioral models and neurophysiologic and neuroimaging strategies have made possible the study of brain circuits. There is growing interest in investigating the developmental trajectory of behaviors from infancy to adulthood and old age. Because anxiety, mood disturbance, repetitive behaviors, and social deficits commonly occur in people with severe ID, those affected are often given multiple psychiatric diagnoses. This has led to considerable confusion in the literature. It is critical to focus on specific behaviors and cognitive patterns in research and not confuse psychiatric symptoms that lack precise definitions and involve multiple genes, the so-called psychiatric phenotype, with the more specific behavioral phenotype. New treatments based on knowledge of underlying neurobiology call for more fine-grained definition of behavior. © 2010 Wiley-Liss, Inc.