The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey

PubMed Central

Turner, Martin R; Swash, Michael

2015-01-01

Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS. PMID:25644224

Women with epilepsy: clinically relevant issues

PubMed Central

Bangar, Santosh; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E.

2016-01-01

Summary Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population. PMID:27678205

Teachers' Perceptions of and Responses to Student Evaluation of Teaching: Purposes and Uses in Clinical Education

ERIC Educational Resources Information Center

Wong, Wai Yee; Moni, Karen

2014-01-01

Student evaluation of teaching (SET) only becomes an effective tool for improving teaching and learning when the relevant stakeholders seriously consider and plan appropriate actions according to student feedback. It is common practice in medical education to provide clinical teachers with student feedback. However, there is limited evidence about…

Prevalence and psychosocial correlates of depressive symptoms in urban Chinese women during midlife.

PubMed

Wong, Carmen K M; Liang, Jun; Chan, Man L; Chan, Yin H; Chan, Laam; Wan, Kwong Y; Ng, Ming S; Chan, Dicken C C; Wong, Samuel Y S; Wong, Martin C S

2014-01-01

Depression is common in women with much research focusing on hormonal changes and menopausal symptoms but with little exploration of psychosocial problems in midlife. This study investigates the prevalence of clinically relevant depressive symptoms in midlife Chinese women and its association with psychosocial factors. A cross-sectional, community-based household survey of women aged 45 to 64 years of age was conducted in Hong Kong from September 2010 to March 2011. The structured questionnaire included demographic data, educational status, marital status and household income, as well as perceived current stressful events and significant life events in the past 12 months. Information on clinically relevant depressive symptoms was measured by the validated chinese Patient Health Questionnaire (PHQ-9). A total of 402 participants were recruited in the study period. Of the 393 women who completed the questionnaire, the prevalence of clinically relevant depressive symptoms (PHQ-9 score≧10) was 11.0%. In multiple regression analysis, being single/divorced/separated/widowed, having an educational level of primary school level or below, having multiple chronic diseases, loss of hobby or loss of close social support in the past 12 months in midlife were associated with clinically relevant depressive symptoms. Correlates of clinically relevant depressive symptoms in midlife Chinese women can be used to identify those at increased risk and potentiate further studies to explore early psychosocial and community interventions.

Clinical correlates of common corneal neovascular diseases: a literature review

PubMed Central

Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal

2015-01-01

A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches.

PubMed

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D'Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches

PubMed Central

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D’Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice. PMID:28083535

The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice

PubMed Central

Markowitz, Geoffrey J.; Kadam, Shilpa D.; Boothe, Dawn M.; Irving, Natasha D.; Comi, Anne M.

2010-01-01

Rodents eliminate antiepileptic drugs (AEDs) faster than humans, creating challenges for designing clinically-relevant protocols. Half-lives of AEDs in immature mice are unknown. The pharmacokinetics of commonly-used AEDs were examined in CD1 mice using a single-dose protocol at post-natal day 19. Following intraperitoneal therapeutic dosing, blood serum concentrations spanning 1–48 hours post-administration and corresponding brain tissue concentrations at 4 hours were analyzed. Half-lives of valproate, phenobarbital, diazepam (and metabolites), phenytoin, and levetiracetam were 2.6, 15.8, 22.3, 16.3, and 3.2 hours respectively, compared to 0.8, 7.5, 7.7, 16.0, and 1.5 hours reported for adult mice. Brain-to-blood ratios were comparable to adult ratios. AEDs tested had longer half-lives and maintained therapeutic plasma concentrations longer than reported in mature mice, making clinically-relevant protocols feasible. PMID:20848732

[Relevant allergans by periorbital allergic contact dermatitis. Oxybuprocain, an underestimated allergen].

PubMed

Blaschke, V; Fuchs, T

2003-08-01

Periorbital allergic contact dermatitis is a rare disease and the main differential diagnoses are atopic and seborrhoeic dermatitis. The diagnosis is based on clinical appearance, patient history and patch testing. Current systematic overviews on contact allergens involved are lacking and with changes in medical preparations, new relevant antigens may emerge. Based on the systematic data of the information network of dermatological clinics (IVDK), patch test reactions in 48,969 patients tested between 1996 and 2000 were evaluated. A total of 763 patients suffered from periorbital dermatitis which was suspected to be due to the use of topical medication. The most common epidermal sensitizations in the general population were observed against nickel and fragrances. In the periorbital dermatitis group, sensitization against local anaesthetics and antibiotics was more frequent than in the general population. In three patients, oxybuprocain was identified as the causative agent, which has not yet been recognized as a common allergen.

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Schlessinger, Daniel I; Iyengar, Sanjana; Yanes, Arianna F; Chiren, Sarah G; Godinez-Puig, Victoria; Chen, Brian R; Kurta, Anastasia O; Schmitt, Jochen; Deckert, Stefanie; Furlan, Karina C; Poon, Emily; Cartee, Todd V; Maher, Ian A; Alam, Murad; Sobanko, Joseph F

2017-07-12

Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials.

Update on Medical Practices that should be questioned in 2015

PubMed Central

Morgan, Daniel J.; Dhruva, Sanket S.; Wright, Scott M.; Korenstein, Deborah

2016-01-01

Importance Overuse of medical care, consisting primarily of overdiagnosis and overtreatment, is a common clinical problem. Objective To identify and highlight articles published in 2014 that are most likely to impact overuse, organized into the categories of overdiagnosis, overtreatment, and methods to avoid overuse. These manuscripts were reviewed and interpreted for their importance to clinical medicine. Evidence Review A structured review of English-language articles on PubMed published in 2014 and review of tables of contents of relevant journals to identify potential articles that related to medical overuse in adults. Findings We reviewed 910 articles, of which 440 addressed overuse. Of these, 104 were deemed most relevant based on the presentation of original data, quality of methodology, magnitude of clinical impact, and the number of patients potentially affected. The 10 most influential articles were selected by author consensus using the same criteria. Findings included lack of benefit for screening pelvic examinations (positive predictive value <5%), carotid artery and thyroid ultrasounds. Harms of cancer screening included unnecessary surgery and complications. Head CT scans were an overused diagnostic test (4% with clinically significant findings) and overtreatment included acetaminophen for low back pain, prolonged opioid use after surgery (3% of patients on >90 days), perioperative aspirin, medications to increase HDL, and stenting for renal artery stenosis. Conclusions and Relevance Many common medical practices should be reconsidered. It is hoped that our review promotes reflection on these 10 articles and lead to questioning other non-evidence based practices. PMID:26551354

Reflections on the present and future of upper limb prostheses.

PubMed

Farina, Dario; Amsüss, Sebastian

2016-01-01

Despite progress in research and media attention on active upper limb prostheses, presently the most common commercial upper limb prosthetic devices are not fundamentally different from solutions offered almost one century ago. Limited information transfer for both control and sensory-motor integration and challenges in socket technology have been major obstacles. By analysing the present state-of-the-art and academic achievements, we provide our opinion on the future of upper limb prostheses. We believe that surgical procedures for muscle reinnervation and osseointegration will become increasingly clinically relevant; muscle electrical signals will remain the main clinical means for prosthetic control; and chronic electrode implants, first in muscles (control), then in nerves (sensory feedback), will become viable clinical solutions. After decades of suspended clinically relevant progress, it is foreseeable that a new generation of upper limb prostheses will enter the market in the near future based on such advances, thereby offering substantial clinical benefit for patients.

DEFINING THE RELEVANT OUTCOME MEASURES IN MEDICAL DEVICE ASSESSMENTS: AN ANALYSIS OF THE DEFINITION PROCESS IN HEALTH TECHNOLOGY ASSESSMENT.

PubMed

Jacobs, Esther; Antoine, Sunya-Lee; Prediger, Barbara; Neugebauer, Edmund; Eikermann, Michaela

2017-01-01

Defining relevant outcome measures for clinical trials on medical devices (MD) is complex, as there is a large variety of potentially relevant outcomes. The chosen outcomes vary widely across clinical trials making the assessment in evidence syntheses very challenging. The objective is to provide an overview on the current common procedures of health technology assessment (HTA) institutions in defining outcome measures in MD trials. In 2012-14, the Web pages of 126 institutions involved in HTA were searched for methodological manuals written in English or German that describe methods for the predefinition process of outcome measures. Additionally, the institutions were contacted by email. Relevant information was extracted. All process steps were performed independently by two reviewers. Twenty-four manuals and ten responses from the email request were included in the analysis. Overall, 88.5 percent of the institutions describe the type of outcomes that should be considered in detail and 84.6 percent agree that the main focus should be on patient relevant outcomes. Specifically related to MD, information could be obtained in 26 percent of the included manuals and email responses. Eleven percent of the institutions report a particular consideration of MD related outcomes. This detailed analysis on common procedures of HTA institutions in the context of defining relevant outcome measures for the assessment of MD shows that standardized procedures for MD from the perspective of HTA institutions are not widespread. This leads to the question if a homogenous approach should be implemented in the field of HTA on MD.

[Heart disease in sports horses: Current recommendations of the 2014 ACVIM / ECEIM consensus statement].

PubMed

Schwarzwald, C

2016-10-01

Heart murmurs and arrhythmias are common in horses. Assessment of their clinical relevance concerning health, performance, safety and longevity of sports horses is of highest importance. A comprehensive cardiovascular examination is crucial for diagnosis and assessment of the severity of disease. Recently, an expert panel of the American College of Veterinary Internal Medicine (ACVIM) and the European College of Equine Internal Medicine (ECEIM) developed a consensus statement containing recommendations for sports horses with heart disease. This article summarizes the most relevant recommendations for practitioners, considering the most common and most important cardiac disorders in adult sports horses. These include mitral, aortic and tricuspid insufficiency, ventricular septal defects, atrial fibrillation as well as supraventricular and ventricular arrhythmias. Despite the fact that most horses with cardiovascular disease maintain a sufficient performance capacity, regular evaluations are indicated in horses with clinically relevant disorders. Under certain circumstances, horses with moderate to severe structural disease, with persistent untreated atrial fibrillation and with certain ventricular arrhythmias might still be used by informed adult riders. Horses with complex ventricular arrhythmias, pulmonary hypertension or congestive heart failure must not be ridden or driven and should be retired.

Potential common factors associated with predisposition to common cold in middle-aged and elderly Japanese: A community-based cross-sectional study.

PubMed

Shibata, Michi; Iwane, Taizo; Higuchi, Ryoko; Suwa, Kaname; Nakajima, Kei

2018-05-01

People worldwide frequently catch a common cold, which occasionally develops into secondary severe conditions such as pneumonia. However, it is unclear whether predisposition to the common cold is associated with the individual's characteristics including age, body weight, lifestyles, diets, and intestinal functions, besides exposure to a responsible pathogen. We addressed this issue epidemiologically considering many relevant clinical factors.We reviewed data from a cross-sectional study consisting of 39,524 apparently healthy Japanese aged 40 to 79 years (26,975 men and 12,549 women) who underwent a checkup in 2007. Self-reported predisposition to common cold (SPCC) and relevant clinical conditions and parameters were considered.We observed no significant difference in most clinical parameters including age, body mass index (BMI), glycated hemoglobin (HbA1c), and prevalence of men and current smokers between subjects with and without SPCC. In univariate analysis, circulating white blood cell (WBC) count and serum alanine-aminotransferase (ALT) were significantly higher in subjects with SPCC than in those without, whereas serum high-density lipoprotein cholesterol (HDL-C) and duration of sleep were lower. In logistic regression analysis after full adjustment for relevant confounding factors, BMI categories except BMI of ≥27.0 kg/m were significantly associated with SPCC compared with BMI of 23.0 to 24.9 kg/m. Short duration of sleep (≤5 hours), occasional alcohol drinking, and no-exercise were significantly associated with SPCC compared with 7 hours sleep duration, no-drinking alcohol, and low frequent exercise (twice per month), respectively. All gastrointestinal disorders (gastric complaints, constipation, and diarrhea) were independently associated with SPCC. Imbalanced diet and taking a snack were also associated with SPCC in a degree dependent manner. Furthermore, WBC count, serum ALT, and HDL-C (as continuous variables) were associated with SPCC (HDL-C was inversely), whereas no significant association was observed between SPCC and age, smoking, HbA1c, and pharmacotherapy for diabetes, hypertension, and dyslipidemia.Our results demonstrated that multifactorial conditions and parameters might be simultaneously associated with the predisposition to common cold. Prospective studies including detailed common cold questionnaire and measurements are needed to confirm currently suspected causative and protective factors.

The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism

PubMed Central

Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C.

2017-01-01

Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288

Prevalence and relevance of the positivity of skin prick testing in patients with chronic urticaria.

PubMed

Kulthanan, Kanokvalai; Jiamton, Sukhum; Rutnin, Ni-on; Insawang, Metavee; Pinkaew, Sumrauy

2008-06-01

Many patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000-2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty-eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One-third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food-induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.

Clinical Scenarios for Discordant Anti-Xa

PubMed Central

Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

2016-01-01

Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

Fragrance contact allergy in Iran.

PubMed

Firooz, A; Nassiri-Kashani, M; Khatami, A; Gorouhi, F; Babakoohi, S; Montaser-Kouhsari, L; Davari, P; Dowlati, Y

2010-12-01

Fragrances are considered as one of the most common causes of allergic contact dermatitis. About 1-4% of the general population suffer from fragrance contact allergy (FCA). To determine the frequency of FCA and its clinical relevance in a sample of Iranian patients with history of contact and/or atopic dermatitis from January 2004 to December 2008. Standardized patch testing with 28-allergen screening series recommended by the German Contact Dermatitis Research Group and European Standard Series was used at six dermatological clinics in Iran. Fragrance allergens comprised of fragrance mix I (FM I), Myroxylon pereirae (MP; balsam of Peru), Lyral, turpentine and FM II. Fragrance contact allergy was detected in 7.2% of the patients. The frequency of positive reactions to FM I, MP and FM II were 3.7% (41/1105), 2.8% (32/1135) and 1.1% (3/267) respectively. 82.4% of the reactions to fragrance allergens were clinically relevant. The most common involved areas were hands (68.4%) and face (35.4%). Fragrance allergy predominantly affected women aged more than 40 years (P=0.008). Positive reaction to more than two allergens was significantly higher in FCA patients compared with other contact dermatitis patients (P<0.0001), and FM I, nickel and MP were the most frequent allergens in these patients. Despite less frequency of FCA in comparison with some European countries, its clinical relevance in Iranian patients seems to be high. It mostly affects the hands and the face predominantly in women aged more than 40 years. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

Coronary artery anomalies overview: The normal and the abnormal

PubMed Central

Villa, Adriana DM; Sammut, Eva; Nair, Arjun; Rajani, Ronak; Bonamini, Rodolfo; Chiribiri, Amedeo

2016-01-01

The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery anatomy. Extensive iconography supports the text, with particular attention to images obtained in vivo using non-invasive imaging. We have divided this article into three groups, according to their frequency in the general population: Normal, normal variant and anomaly. Although congenital coronary artery anomalies are relatively uncommon, they are the second most common cause of sudden cardiac death among young athletes and therefore warrant detailed review. Based on the functional relevance of each abnormality, coronary artery anomalies can be classified as anomalies with obligatory ischemia, without ischemia or with exceptional ischemia. The clinical symptoms may include chest pain, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia, myocardial infarction and sudden cardiac death. Moreover, it is important to also identify variants and anomalies without clinical relevance in their own right as complications during surgery or angioplasty can occur. PMID:27358682

Detection of clinically relevant copy number alterations in oral cancer progression using multiplexed droplet digital PCR.

PubMed

Hughesman, Curtis B; Lu, X J David; Liu, Kelly Y P; Zhu, Yuqi; Towle, Rebecca M; Haynes, Charles; Poh, Catherine F

2017-09-19

Copy number alterations (CNAs), a common genomic event during carcinogenesis, are known to affect a large fraction of the genome. Common recurrent gains or losses of specific chromosomal regions occur at frequencies that they may be considered distinctive features of tumoral cells. Here we introduce a novel multiplexed droplet digital PCR (ddPCR) assay capable of detecting recurrent CNAs that drive tumorigenesis of oral squamous cell carcinoma. Applied to DNA extracted from oral cell lines and clinical samples of various disease stages, we found good agreement between CNAs detected by our ddPCR assay with those previously reported using comparative genomic hybridization or single nucleotide polymorphism arrays. Furthermore, we demonstrate that the ability to target specific locations of the genome permits detection of clinically relevant oncogenic events such as small, submicroscopic homozygous deletions. Additional capabilities of the multiplexed ddPCR assay include the ability to infer ploidy level, quantify the change in copy number of target loci with high-level gains, and simultaneously assess the status and viral load for high-risk human papillomavirus types 16 and 18. This novel multiplexed ddPCR assay therefore may have clinical value in differentiating between benign oral lesions from those that are at risk of progressing to oral cancer.

Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia

PubMed Central

Maharaj, R.

2012-01-01

Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. The spectrum of diastolic disease extends from the asymptomatic phase to fulminant cardiac failure. These patients are commonly encountered in operating rooms and critical care units. A clearer understanding of the underlying pathophysiology and clinical implications of HF with a preserved ejection fraction is fundamental to directing further research and to evaluate interventions. This review highlights the impact of diastolic dysfunction and HF with a preserved ejection fraction during the perioperative period and during critical illness. PMID:23960679

Transsphenoidal Surgery for Pituitary Tumors and Other Sellar Masses.

PubMed

Owen, Tina J; Martin, Linda G; Chen, Annie V

2018-01-01

Transsphenoidal surgery is an option for dogs and cats with functional and nonfunctional pituitary masses or other sellar and parasellar masses. An adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most common clinically relevant pituitary tumor in dogs, and the most common pituitary tumor seen in cats is a growth hormone-secreting tumor causing acromegaly. Transsphenoidal surgery can lead to rapid resolution of clinical signs and provide a cure for these patients. Because of the risks associated with this surgery, it should only be attempted by a cohesive pituitary surgery group with a sophisticated medical and surgical team. Copyright © 2017 Elsevier Inc. All rights reserved.

Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

PubMed Central

Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

2015-01-01

Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species.

PubMed

Alanio, A; Beretti, J-L; Dauphin, B; Mellado, E; Quesne, G; Lacroix, C; Amara, A; Berche, P; Nassif, X; Bougnoux, M-E

2011-05-01

New Aspergillus species have recently been described with the use of multilocus sequencing in refractory cases of invasive aspergillosis. The classical phenotypic identification methods routinely used in clinical laboratories failed to identify them adequately. Some of these Aspergillus species have specific patterns of susceptibility to antifungal agents, and misidentification may lead to inappropriate therapy. We developed a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based strategy to adequately identify Aspergillus species to the species level. A database including the reference spectra of 28 clinically relevant species from seven Aspergillus sections (five common and 23 unusual species) was engineered. The profiles of young and mature colonies were analysed for each reference strain, and species-specific spectral fingerprints were identified. The performance of the database was then tested on 124 clinical and 16 environmental isolates previously characterized by partial sequencing of the β-tubulin and calmodulin genes. One hundred and thirty-eight isolates of 140 (98.6%) were correctly identified. Two atypical isolates could not be identified, but no isolate was misidentified (specificity: 100%). The database, including species-specific spectral fingerprints of young and mature colonies of the reference strains, allowed identification regardless of the maturity of the clinical isolate. These results indicate that MALDI-TOF MS is a powerful tool for rapid and accurate identification of both common and unusual species of Aspergillus. It can give better results than morphological identification in clinical laboratories. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Evidence-Based Indicators of Neuropsychological Change in the Individual Patient: Relevant Concepts and Methods

PubMed Central

Duff, Kevin

2012-01-01

Repeated assessments are a relatively common occurrence in clinical neuropsychology. The current paper will review some of the relevant concepts (e.g., reliability, practice effects, alternate forms) and methods (e.g., reliable change index, standardized based regression) that are used in repeated neuropsychological evaluations. The focus will be on the understanding and application of these concepts and methods in the evaluation of the individual patient through examples. Finally, some future directions for assessing change will be described. PMID:22382384

The anatomy of the anterior cruciate ligament and its relevance to the technique of reconstruction.

PubMed

Śmigielski, R; Zdanowicz, U; Drwięga, M; Ciszek, B; Williams, A

2016-08-01

Anterior cruciate ligament (ACL) reconstruction is commonly performed and has been for many years. Despite this, the technical details related to ACL anatomy, such as tunnel placement, are still a topic for debate. In this paper, we introduce the flat ribbon concept of the anatomy of the ACL, and its relevance to clinical practice. Cite this article: Bone Joint J 2016;98-B:1020-6. ©2016 The British Editorial Society of Bone & Joint Surgery.

Drug-drug interactions as a result of co-administering Δ9-THC and CBD with other psychotropic agents.

PubMed

Rong, Carola; Carmona, Nicole E; Lee, Yena L; Ragguett, Renee-Marie; Pan, Zihang; Rosenblat, Joshua D; Subramaniapillai, Mehala; Shekotikhina, Margarita; Almatham, Fahad; Alageel, Asem; Mansur, Rodrigo; Ho, Roger C; McIntyre, Roger S

2018-01-01

To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents. Areas covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. Expert opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Adding ultrasound to clinical examination reduced frequency of enthesitis in primary care psoriasis patients with musculoskeletal complaints.

PubMed

van der Ven, Myrthe; Karreman, Maren C; Weel, Angelique E A M; Tchetverikov, Ilja; Vis, Marijn; Nijsten, Tamar E C; Hazes, Johanna M W; Luime, Jolanda J

2016-01-01

Part of the psoriasis patients with musculoskeletal complaints will have inflammation of the entheses. Entheseal inflammation is difficult to assess by clinical examination only. Therefore, we aimed to determine the frequency of clinically relevant ultrasound inflammation at the most commonly assessed entheses (MASEI; Madrid Sonographic Enthesis Index) in primary care psoriasis patients with one or more tender entheses. Adult primary care psoriasis patients with musculoskeletal complaints (tender enthesis or arthritis at physical examination) had an ultrasound examination of seven entheses according to the MASEI. Clinically relevant ultrasound inflammation was defined as active inflammation on ultrasound in combination with at least one clinical feature at the same enthesis. Active ultrasound inflammation contained positive power Doppler signal or in case of the plantar aponeurosis increased thickness. Structural changes entailed calcifications, enthesophytes, increased thickness, hypoechogeneicity indicating irregular fibre structure and erosions. Clinically, an enthesis was scored positive by a tender enthesis at clinical examination, reported pain in the history or self-reported pain in the questionnaires. Of 542 primary care psoriasis patient, 111 patients had tender entheses and/or arthritis. These patients were both clinically and ultrasonographically evaluated. Active ultrasound inflammation accompanied with pain or tenderness at the enthesis was found in 36% of the patients (n=40). Most common were inflammation at the knee (n=11) and at the plantar aponeurosis (n=10). Structural changes were observed in 95% of the psoriasis patients independent of their clinical manifestation. We found concurrent presence of ultrasound inflammatory changes and clinical symptoms in 36% of the primary care psoriasis patients who had tenderness at one or more entheseal sites.

Medical treatment of acquired nystagmus.

PubMed

Ehrhardt, David; Eggenberger, Eric

2012-11-01

This article synthesises recent findings and addresses relevant anatomy, pathophysiologic considerations, and current treatment options for common forms of acquired nystagmus including vestibular and gaze holding dysfunction. Some forms of nystagmus have relatively specific treatments, such as baclofen for periodic alternating nystagmus, and repositioning for benign paroxysmal positional vertigo. Recent studies have brought changes to many of the treatments of nystagmus variants. Additionally, other recent advances in nystagmus treatment, like the usage of 4-aminopyridine, have added potent medications to the physician's armamentarium. Nystagmus is a commonly encountered entity in clinical practice. However, evidence supported treatments are scarce. Medical treatment of nystagmus is difficult, with often limited and variable response to pharmacologic therapies. This mandates a continued re-evaluation of patients and creation of an individualized approach to this common clinical problem.

The Genus Corynebacterium and Other Medically Relevant Coryneform-Like Bacteria

PubMed Central

2012-01-01

Catalase-positive Gram-positive bacilli, commonly called “diphtheroids” or “coryneform” bacteria were historically nearly always dismissed as contaminants when recovered from patients, but increasingly have been implicated as the cause of significant infections. These taxa have been underreported, and the taxa were taxonomically confusing. The mechanisms of pathogenesis, especially for newly described taxa, were rarely studied. Antibiotic susceptibility data were relatively scant. In this minireview, clinical relevance, phenotypic and genetic identification methods, matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) evaluations, and antimicrobial susceptibility testing involving species in the genus Corynebacterium and other medically relevant Gram-positive rods, collectively called coryneforms, are described. PMID:22837327

Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level

USDA-ARS?s Scientific Manuscript database

Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its...

Hypercalcemic crisis: a clinical review.

PubMed

Ahmad, Shazia; Kuraganti, Gayatri; Steenkamp, Devin

2015-03-01

Hypercalcemia is a common metabolic perturbation. However, hypercalcemic crisis is an unusual endocrine emergency, with little clinical scientific data to support therapeutic strategy. We review the relevant scientific English literature on the topic and review current management strategies after conducting a PubMed, MEDLINE, and Google Scholar search for articles published between 1930 and June 2014 using specific keywords: "hypercalcemic crisis," "hyperparathyroid crisis," "parathyroid storm," "severe primary hyperparathyroidism," "acute hyperparathyroidism," and "severe hypercalcemia" for articles pertaining to the diagnosis, epidemiology, clinical presentation, and treatment strategies. Despite extensive clinical experience, large and well-designed clinical studies to direct appropriate clinical care are lacking. Nonetheless, morbidity and mortality rates have substantially decreased since early series reported almost universal fatality. Improved outcomes can be attributed to modern diagnostic capabilities, leading to earlier diagnosis, along with the recognition that primary hyperparathyroidism is the most common etiology for hypercalcemic crisis. Hypercalcemic crisis is an unusual endocrine emergency that portends excellent outcomes if rapid diagnosis, medical treatment, and definitive surgical treatment are expedited. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

PubMed Central

Busetti, Alessandro; Thompson, Thomas P.; Tegazzini, Diana; Megaw, Julianne; Maggs, Christine A.; Gilmore, Brendan F.

2015-01-01

The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds. PMID:26058011

Nitric oxide-releasing polyacrylonitrile disperses biofilms formed by wound-relevant pathogenic bacteria.

PubMed

Craven, M; Kasper, S H; Canfield, M J; Diaz-Morales, R R; Hrabie, J A; Cady, N C; Strickland, A D

2016-04-01

To test the antimicrobial and antibiofilm properties of a nitric oxide (NO)-releasing polymer against wound-relevant bacterial pathogens. Using a variety of 96-well plate assay systems that include standard well plates and the minimum biofilm eradication concentration biofilm assay well plate, a NO-releasing polymer based on (poly)acrylonitrile (PAN/NO) was studied for antimicrobial and antibiofilm activity against the common wound pathogens Pseudomonas aeruginosa (PAO1), Staphylococcus aureus (Mu50) and Enterococcus faecalis (V583). The polymer was capable of dispersing single-species biofilms of Ps. aeruginosa as well as a more clinically relevant multispecies biofilm that incorporates Ps. aeruginosa along with Staph. aureus and Ent. faecalis. PAN/NO also synergistically enhanced the susceptibility of the multispecies biofilms to the common broad-spectrum antibiotic, ciprofloxacin. Multiple in vitro biocompatibility assays show that PAN/NO has limited potential for mammalian cytotoxicity. This study demonstrates the feasibility of utilizing the NO-releasing polymer, PAN/NO, to manage biofilms formed by wound-relevant pathogens, and provides proof-of-concept for use of this NO-releasing polymer platform across multiple disciplines where bacterial biofilms pose significant problems. In the clinical sector, bacterial biofilms represent a substantial treatment challenge for health care professionals and are widely recognized as a key factor in prolonging patient morbidity. This study highlights the potential role for the ubiquitous signalling molecule nitric oxide (NO) as an antibiofilm therapy. © 2016 The Society for Applied Microbiology.

FDA: Evidentiary Standards for Drug Development and Approval

PubMed Central

Katz, Russell

2004-01-01

Summary: The United States Food and Drug Administration is charged with approving drug treatments that have been shown to be safe and effective. Relevant statutes and regulations provide a legal framework for establishing safety and effectiveness that is sufficiently flexible to ensure that appropriate scientific data are collected for specific treatments targeted to particular diseases. Nonetheless, all clinical trials proposed to establish effectiveness must incorporate common elements in order for the appropriate legal and scientific standards of drug approval to be met. This article will discuss the relevant laws and regulations pertaining to the current effectiveness standard and will discuss the most important clinical trial design elements currently considered acceptable for applications for treatments of neurologic and psychiatric illness. PMID:15717032

Attention to Local Health Burden and the Global Disparity of Health Research

PubMed Central

Evans, James A.; Shim, Jae-Mahn; Ioannidis, John P. A.

2014-01-01

Most studies on global health inequality consider unequal health care and socio-economic conditions but neglect inequality in the production of health knowledge relevant to addressing disease burden. We demonstrate this inequality and identify likely causes. Using disability-adjusted life years (DALYs) for 111 prominent medical conditions, assessed globally and nationally by the World Health Organization, we linked DALYs with MEDLINE articles for each condition to assess the influence of DALY-based global disease burden, compared to the global market for treatment, on the production of relevant MEDLINE articles, systematic reviews, clinical trials and research using animal models vs. humans. We then explored how DALYs, wealth, and the production of research within countries correlate with this global pattern. We show that global DALYs for each condition had a small, significant negative relationship with the production of each type of MEDLINE articles for that condition. Local processes of health research appear to be behind this. Clinical trials and animal studies but not systematic reviews produced within countries were strongly guided by local DALYs. More and less developed countries had very different disease profiles and rich countries publish much more than poor countries. Accordingly, conditions common to developed countries garnered more clinical research than those common to less developed countries. Many of the health needs in less developed countries do not attract attention among developed country researchers who produce the vast majority of global health knowledge—including clinical trials—in response to their own local needs. This raises concern about the amount of knowledge relevant to poor populations deficient in their own research infrastructure. We recommend measures to address this critical dimension of global health inequality. PMID:24691431

Attention to local health burden and the global disparity of health research.

PubMed

Evans, James A; Shim, Jae-Mahn; Ioannidis, John P A

2014-01-01

Most studies on global health inequality consider unequal health care and socio-economic conditions but neglect inequality in the production of health knowledge relevant to addressing disease burden. We demonstrate this inequality and identify likely causes. Using disability-adjusted life years (DALYs) for 111 prominent medical conditions, assessed globally and nationally by the World Health Organization, we linked DALYs with MEDLINE articles for each condition to assess the influence of DALY-based global disease burden, compared to the global market for treatment, on the production of relevant MEDLINE articles, systematic reviews, clinical trials and research using animal models vs. humans. We then explored how DALYs, wealth, and the production of research within countries correlate with this global pattern. We show that global DALYs for each condition had a small, significant negative relationship with the production of each type of MEDLINE articles for that condition. Local processes of health research appear to be behind this. Clinical trials and animal studies but not systematic reviews produced within countries were strongly guided by local DALYs. More and less developed countries had very different disease profiles and rich countries publish much more than poor countries. Accordingly, conditions common to developed countries garnered more clinical research than those common to less developed countries. Many of the health needs in less developed countries do not attract attention among developed country researchers who produce the vast majority of global health knowledge--including clinical trials--in response to their own local needs. This raises concern about the amount of knowledge relevant to poor populations deficient in their own research infrastructure. We recommend measures to address this critical dimension of global health inequality.

Actinic prurigo of the lip: Two case reports

PubMed Central

Miranda, Ana MO; Ferrari, Thiago M; Werneck, Juliana T; Junior, Arley Silva; Cunha, Karin S; Dias, Eliane P

2014-01-01

Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high-altitude living people, mainly in indigenous descendants. The diagnosis of actinic prurigo can be challenging, mainly when lip lesions are the only manifestation, which is not a common clinical presentation. The aim of this article is to report two cases of actinic prurigo showing only lip lesions. The patients were Afro-American and were unaware of possible Indian ancestry. Clinical exam, photographs, videoroscopy examination and biopsy were performed, and the diagnosis of actinic prurigo was established. Topical corticosteroid and lip balm with ultraviolet protection were prescribed with excellent results. The relevance of this report is to show that although some patients may not demonstrate the classical clinical presentation of actinic prurigo, the associated clinical and histological exams are determinants for the correct diagnosis and successful treatment of this disease. PMID:25133153

Clinical utility of marketing terms used for over-the-counter dermatologic products.

PubMed

Boozalis, Emily; Patel, Shivani

2018-05-08

Cosmetic products are commonly marketed using dermatologic terms such as 'hypoallergenic', 'non-comedogenic', 'fragrance-free', etc. The clinical relevance of these claims can be confusing to both patients and clinicians. A systematic review was performed via a PubMed search of published articles from January 1985 to October 2017 to further describe and elucidate the clinical utility of a predefined list of common dermatologic terms used by pharmaceutical companies to market over-the-counter products. The terms 'fragrance-free', 'hypoallergenic', 'non-comedogenic', and 'oil-free' on cosmetic product labels are not regulated by any governing body and provide varied clinical utility. Products labeled as having 'natural ingredients' are not necessarily safer or less irritating to patients with atopy or a history of allergic contact dermatitis. Despite the increasing popularity of 'paraben-free' cosmetics, parabens are safe for patients in the quantities used in cosmetic products and can be safely used in patients who do not exhibit contact dermatitis to this preservative. A working knowledge of common cosmetic ingredients may help dermatologists to counsel patients on which products to avoid for their specific dermatologic conditions.

Frequency of Toxocariasis among Patients Clinically Suspected to Have Visceral Toxocariasis: A Retrospective Descriptive Study in Sri Lanka

PubMed Central

Iddawela, Devika; Ehambaram, Kiruthiha; Pethiyagoda, Kalyani; Bandara, Lakmalee

2017-01-01

Introduction Human toxocariasis is caused by several species of the nematode Toxocara. Two common clinical syndromes are ocular and visceral larva migrans. Objectives To determine the Toxocara antibody positivity in clinically suspected VLM patients and to describe demographic factors and clinical manifestations of seropositive patients. Methods 522 clinically suspected patients were studied between 1993 and 2014. Relevant data was gathered from referral letters. Serum samples were subjected to Toxocara antigen ELISA. Results Overall, seropositivity was 50.2% (262), of which 109 (40.8%) were positive at high level of Toxocara antibody carriage and 153 (58.4%) were positive at low levels. The seropositives ranged from 3 months to 70 years (mean = 7.8). Younger age group had higher levels of seropositivity and it was statistically significant. Majority of children under 5 years were seropositive (47.7%, n = 125). Seropositivity was common in males (55.3%, n = 145). Clinical manifestations of seropositives include lymphadenopathy (24.1%) skin rash (22.5%), dyspnoea (21.7%), fever (21%), hepatosplenomegaly (9.2%), and abdominal pain (3.8%). 197 (75.2%) seropositive cases had eosinophilia. These symptoms were not statistically significant. Conclusions This study confirms toxocariasis as an important cause of childhood ill health identifying common clinical symptoms recommending preventive measures to limit transmission. PMID:29362672

Requirements for the formal representation of pathophysiology mechanisms by clinicians

PubMed Central

Helvensteijn, M.; Kokash, N.; Martorelli, I.; Sarwar, D.; Islam, S.; Grenon, P.; Hunter, P.

2016-01-01

Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for pathophysiology mechanisms. A number of obstacles stand in the way of this sharing—not least the technical and operational challenges that must be overcome to ensure that (i) the explicit biological meanings of the Physiome's quantitative methods to represent mechanisms are open to articulation, verification and study by clinicians, and that (ii) clinicians are given the tools and training to explicitly express disease manifestations in direct contribution to modelling. To this end, the Physiome and Clinical communities must co-develop a common computational toolkit, based on this blueprint, to bridge the representation of knowledge of pathophysiology mechanisms (a) that is implicitly depicted in electronic health records and the literature, with (b) that found in mathematical models explicitly describing mechanisms. In particular, this paper makes use of a step-wise description of a specific disease mechanism as a means to elicit the requirements of representing pathophysiological meaning explicitly. The computational blueprint developed from these requirements addresses the Clinical community goals to (i) organize and manage healthcare resources in terms of relevant disease-related knowledge of mechanisms and (ii) train the next generation of physicians in the application of quantitative methods relevant to their research and practice. PMID:27051514

[Contact allergy to dexpanthenol].

PubMed

Schulze-Dirks, A; Frosch, P J

1988-06-01

Eleven cases of contact allergy to dexpanthenol are reported (5 females, 6 males; mean age 62.4 years). Five patients suffered from a leg ulcer and/or stasis dermatitis. In five patients the sensitization occurred after the application of dexpanthenol-containing ointments to the face. Only one patient did not show sensitization to other common allergens. Three patients were sensitive to wool wax alcohols, which are present in a commonly used product. Dexpanthenol seems to be a rare sensitizer, yet clinically most relevant for patients with stasis dermatitis and multiple allergies.

Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death

ERIC Educational Resources Information Center

Novaleski, Carolyn K.; Carter, Bruce D.; Sivasankar, M. Preeti; Ridner, Sheila H.; Dietrich, Mary S.; Rousseau, Bernard

2017-01-01

Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold…

Spiders in dermatology.

PubMed

Kang, Jun K; Bhate, Chinmoy; Schwartz, Robert A

2014-09-01

Spider bites represent an unusual and potentially over-represented clinical diagnosis. Despite a common fear of spiders, known as arachnophobia, current knowledge suggests that only a small number of families within the order Araneae are medically relevant. Moreover, most cutaneous spider reactions, including both evenomations and physical trauma, produce mild, local symptoms which may be managed with supportive care alone. The differential diagnosis for spider bites may be broad, especially if the offending arachnid is not seen or found. We describe a series of spiders relevant to the dermatologist in the United States.

Management of proximal interphalangeal joint injuries

PubMed Central

Freiberg, Arnis

2007-01-01

Injuries to the proximal interphalangeal joint are common but frequently missed. They are often overtreated by prolonged immobilization, resulting in stiffness, which may be permanent. The purpose of the present article is to briefly review the relevant anatomy and biomechanics, present an approach to physical examination and diagnosis, and propose a practical clinical classification. The treatment of the most severe injury – the intra-articular fracture dislocation – is controversial. The various treatment options are discussed, based on personal experience and a review of the literature. A list of relevant references is presented. PMID:19554177

Developing an International Register of Clinical Prediction Rules for Use in Primary Care: A Descriptive Analysis

PubMed Central

Keogh, Claire; Wallace, Emma; O’Brien, Kirsty K.; Galvin, Rose; Smith, Susan M.; Lewis, Cliona; Cummins, Anthony; Cousins, Grainne; Dimitrov, Borislav D.; Fahey, Tom

2014-01-01

PURPOSE We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems. PMID:25024245

Linking the Tinnitus Questionnaire and the subjective Clinical Global Impression: Which differences are clinically important?

PubMed Central

2012-01-01

Background Development of new tinnitus treatments requires prospective placebo-controlled randomized trials to prove their efficacy. The Tinnitus Questionnaire (TQ) is a validated and commonly used instrument for assessment of tinnitus severity and has been used in many clinical studies. Defining the Minimal Clinically Important Difference (MCID) for TQ changes is an important step to a better interpretation of the clinical relevance of changes observed in clinical trials. In this study we aimed to estimate the minimum change of the TQ score that could be considered clinically relevant. Methods 757 patients with chronic tinnitus were pooled from the TRI database and the RESET study. An anchor-based approach using the Clinical Global Impression (CGI) scale and distributional approaches were used to estimate MCID. Receiver Operating Characteristic (ROC) curves were calculated to define optimal TQ change cutoffs discriminating between minimally changed and unchanged subjects. Results The relationship between TQ change scores and CGI ratings of change was good (r = 0.52, p < 0.05). Mean change scores associated with minimally better and minimally worse CGI categories were −6.65 and +2.72 respectively. According to the ROC method MCID for improvement was −5 points and for deterioration +1 points. Conclusion Distribution and anchor-based methods yielded comparable results in identifying MCIDs. ΔTQ scores of −5 and +1 points were identified as the minimal clinically relevant change for improvement and worsening respectively. The asymmetry of the MCIDs for improvement and worsening may be related to expectation effects. PMID:22781703

Dysmorphic features and developmental outcome of 2-year-old children.

PubMed

Seggers, Jorien; Haadsma, Maaike L; Bos, Arend F; Heineman, Maas Jan; Middelburg, Karin J; van den Heuvel, Edwin R; Hadders-Algra, Mijna

2014-11-01

The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. In our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39 weeks, [range 30-43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference -2.53, 95% confidence interval [CI] -4.23 to -0.83) and fluency score (difference -0.62, 95% CI -1.1 to -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations. © 2014 Mac Keith Press.

Effectiveness-implementation Hybrid Designs

PubMed Central

Curran, Geoffrey M.; Bauer, Mark; Mittman, Brian; Pyne, Jeffrey M.; Stetler, Cheryl

2013-01-01

Objectives This study proposes methods for blending design components of clinical effectiveness and implementation research. Such blending can provide benefits over pursuing these lines of research independently; for example, more rapid translational gains, more effective implementation strategies, and more useful information for decision makers. This study proposes a “hybrid effectiveness-implementation” typology, describes a rationale for their use, outlines the design decisions that must be faced, and provides several real-world examples. Results An effectiveness-implementation hybrid design is one that takes a dual focus a priori in assessing clinical effectiveness and implementation. We propose 3 hybrid types: (1) testing effects of a clinical intervention on relevant outcomes while observing and gathering information on implementation; (2) dual testing of clinical and implementation interventions/strategies; and (3) testing of an implementation strategy while observing and gathering information on the clinical intervention’s impact on relevant outcomes. Conclusions The hybrid typology proposed herein must be considered a construct still in evolution. Although traditional clinical effectiveness and implementation trials are likely to remain the most common approach to moving a clinical intervention through from efficacy research to public health impact, judicious use of the proposed hybrid designs could speed the translation of research findings into routine practice. PMID:22310560

Clinical studies of fiber posts: a literature review.

PubMed

Cagidiaco, Maria C; Goracci, Cecilia; Garcia-Godoy, Franklin; Ferrari, Marco

2008-01-01

This literature review aimed to find answers to relevant questions regarding the clinical outcome of endontically treated teeth restored with fiber posts. All clinical studies published since 1990 in journals indexed in MEDLINE were retrieved by searching PubMed with the query terms "fiber posts and clinical studies." The reference list of the collected articles was also screened for further relevant citations. The strength of the evidence provided by the reviewed papers was assessed according to the criteria of evidence-based dentistry. Five randomized controlled trials (RCTs) on fiber posts have been published in peer-reviewed journals. A meta-analysis is not applicable to these studies since they do not address the same specific clinical question. Retrospective and prospective trials without controls are also available. Two RCTs indicate that fiber-reinforced composite posts outperform metal posts in the restoration of endontically treated teeth. However, this evidence cannot be considered as conclusive. Longer-term RCTs would be desirable. The placement of a fiber-reinforced composite post protects against failure, especially under conditions of extensive coronal destruction. The most common type of failure with fiber-reinforced composite posts is debonding.

[Antibiotic management of presumptive bacterial meningitis in adults (rational, methods, course, and follow-up)].

PubMed

Ansart, S

2009-01-01

The annual incidence of community acquired meningitis ranges between 0.6 and four per 100,000 adults in industrialized countries. The most common causative bacteria are Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes. The emergence of resistance to antibiotics, especially for S. pneumoniae, could explain the clinical failure of third generation cephalosporins used to treat adults with S. pneumoniae meningitis. The present therapeutic suggestions are more based on the extrapolation of an experimental model than on relevant clinical trials.

Advances in diagnostic and treatment modalities for intracranial tumors.

PubMed

Dickinson, P J

2014-01-01

Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Imaging Diagnosis of Splanchnic Venous Thrombosis

PubMed Central

Rajesh, S.; Mukund, Amar

2015-01-01

Splanchnic vein thrombosis (SVT) is a broad term that includes Budd-Chiari syndrome and occlusion of veins that constitute the portal venous system. Due to the common risk factors involved in the pathogenesis of these clinically distinct disorders, concurrent involvement of two different regions is quite common. In acute and subacute SVT, the symptoms may overlap with a variety of other abdominal emergencies while in chronic SVT, the extent of portal hypertension and its attendant complications determine the clinical course. As a result, clinical diagnosis is often difficult and is frequently reliant on imaging. Tremendous improvements in vascular imaging in recent years have ensured that this once rare entity is being increasingly detected. Treatment of acute SVT requires immediate anticoagulation. Transcatheter thrombolysis or transjugular intrahepatic portosystemic shunt is used in the event of clinical deterioration. In cases with peritonitis, immediate laparotomy and bowel resection may be required for irreversible bowel ischemia. In chronic SVT, the underlying cause should be identified and treated. The imaging manifestations of the clinical syndromes resulting from SVT are comprehensively discussed here along with a brief review of the relevant clinical features and therapeutic approach. PMID:26600801

Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission.

PubMed

Weinstock, Michael B; Weingart, Scott; Orth, Frank; VanFossen, Douglas; Kaide, Colin; Anderson, Judy; Newman, David H

2015-07-01

Patients with potentially ischemic chest pain are commonly admitted to the hospital or observed after a negative evaluation in the emergency department (ED) owing to concern about adverse events. Previous studies have looked at 30-day mortality, but no current large studies have examined the most important information regarding ED disposition: the short-term risk for a clinically relevant adverse cardiac event (including inpatient ST-segment elevation myocardial infarction, life-threatening arrhythmia, cardiac or respiratory arrest, or death). To determine the incidence of clinically relevant adverse cardiac events in patients hospitalized for chest pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings. We conducted a blinded data review of 45,416 encounters obtained from a prospectively collected database enrolling adult patients admitted or observed with the following inclusion criteria: (1) primary presenting symptom of chest pain, chest tightness, chest burning, or chest pressure and (2) negative findings for serial biomarkers. Data were collected and analyzed from July 1, 2008, through June 30, 2013, from the EDs of 3 community teaching institutions with an aggregate census of more than 1 million visits. We analyzed data extracted by hypothesis-blinded abstractors. The primary outcome was a composite of life-threatening arrhythmia, inpatient ST-segment elevation myocardial infarction, cardiac or respiratory arrest, or death during hospitalization. Of the 45,416 encounters, 11,230 met criteria for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83% of patients arrived by ambulance and 55.00% of patients were women. Relevant history included hypertension in 46.00%, diabetes mellitus in 19.72%, and myocardial infarction in 13.16%. The primary end point occurred in 20 of the 11 230 patients (0.18% [95% CI, 0.11%-0.27%]). After excluding patients with abnormal vital signs, electrocardiographic ischemia, left bundle branch block, or a pacemaker rhythm, we identified a primary end point event in 4 of 7266 patients (0.06% [95% CI, 0.02%-0.14%]). Of these events, 2 were noncardiac and 2 were possibly iatrogenic. In adult patients with chest pain admitted with 2 negative findings for serial biomarkers, nonconcerning vital signs, and nonischemic electrocardiographic findings, short-term clinically relevant adverse cardiac events were rare and commonly iatrogenic, suggesting that routine inpatient admission may not be a beneficial strategy for this group.

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

PubMed

Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

2016-01-01

Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Effectiveness-implementation hybrid designs: combining elements of clinical effectiveness and implementation research to enhance public health impact.

PubMed

Curran, Geoffrey M; Bauer, Mark; Mittman, Brian; Pyne, Jeffrey M; Stetler, Cheryl

2012-03-01

This study proposes methods for blending design components of clinical effectiveness and implementation research. Such blending can provide benefits over pursuing these lines of research independently; for example, more rapid translational gains, more effective implementation strategies, and more useful information for decision makers. This study proposes a "hybrid effectiveness-implementation" typology, describes a rationale for their use, outlines the design decisions that must be faced, and provides several real-world examples. An effectiveness-implementation hybrid design is one that takes a dual focus a priori in assessing clinical effectiveness and implementation. We propose 3 hybrid types: (1) testing effects of a clinical intervention on relevant outcomes while observing and gathering information on implementation; (2) dual testing of clinical and implementation interventions/strategies; and (3) testing of an implementation strategy while observing and gathering information on the clinical intervention's impact on relevant outcomes. The hybrid typology proposed herein must be considered a construct still in evolution. Although traditional clinical effectiveness and implementation trials are likely to remain the most common approach to moving a clinical intervention through from efficacy research to public health impact, judicious use of the proposed hybrid designs could speed the translation of research findings into routine practice.

Clinical features of olfactory disorders in patients seeking medical consultation

PubMed Central

Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

2013-01-01

Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

A study on specialist or special disease clinics based on big data.

PubMed

Fang, Zhuyuan; Fan, Xiaowei; Chen, Gong

2014-09-01

Correlation analysis and processing of massive medical information can be implemented through big data technology to find the relevance of different factors in the life cycle of a disease and to provide the basis for scientific research and clinical practice. This paper explores the concept of constructing a big medical data platform and introduces the clinical model construction. Medical data can be collected and consolidated by distributed computing technology. Through analysis technology, such as artificial neural network and grey model, a medical model can be built. Big data analysis, such as Hadoop, can be used to construct early prediction and intervention models as well as clinical decision-making model for specialist and special disease clinics. It establishes a new model for common clinical research for specialist and special disease clinics.

Pulmonary atelectasis in newborns with clinically treatable diseases who are on mechanical ventilation: clinical and radiological aspects.

PubMed

Dominguez, Mariana Chiaradia; Alvares, Beatriz Regina

2018-01-01

To analyze the radiological aspects of pulmonary atelectasis in newborns on mechanical ventilation and treated in an intensive care unit, associating the characteristics of atelectasis with the positioning of the head and endotracheal tube seen on the chest X-ray, as well as with the clinical variables. This was a retrospective cross-sectional study of 60 newborns treated between 1985 and 2015. Data were collected from medical records and radiology reports. To identify associations between variables, we used Fisher's exact test. The level of significance was set at p < 0.05. The clinical characteristics associated with improper positioning of the endotracheal tube were prematurity and a birth weight of less than 1000 g. Among the newborns evaluated, the most common comorbidity was hyaline membrane disease. Atelectasis was seen most frequently in the right upper lobe, although cases of total atelectasis were more common in the left lung. Malpositioning of the head showed a trend toward an association with atelectasis in the left upper lobe. Pulmonary atelectasis is a common complication in newborns on mechanical ventilation. Radiological evaluation of the endotracheal tube placement provides relevant information for the early correction of this condition.

What does the MADRS mean? Equipercentile linking with the CGI using a company database of mirtazapine studies.

PubMed

Leucht, Stefan; Fennema, Hein; Engel, Rolf R; Kaspers-Janssen, Marion; Lepping, Peter; Szegedi, Armin

2017-03-01

Little is known about the clinical relevance of the Montgomery Asberg Depression Rating Scale (MADRS) total scores. It is unclear how total scores translate into clinical severity, or how commonly used measures for response (reduction from baseline of ≥50% in the total score) translate into clinical relevance. Moreover, MADRS based definitions of remission vary. We therefore compared: a/ the MADRS total score with the Clinical Global Impression - Severity Score (CGI-S) b/ the percentage and absolute change in the MADRS total scores with Clinical Global Impression - Improvement (CGI-I); c/ the absolute and percentage change in the MADRS total scores with CGI-S absolute change. The method used was equipercentile linking of MADRS and CGI ratings from 22 drug trials in patients with Major Depressive Disorder (MDD) (n=3288). Our results confirm the validity of the commonly used measures for response in MDD trials: a CGI-I score of 2 ('much improved') corresponded to a percentage MADRS reduction from baseline of 48-57%, and a CGI-I score of 1 ('very much improved') to a reduction of 80-84%. If a state of almost complete absence of symptoms were required for a definition of remission, a MADRS total score would be <8, because such scores corresponded to a CGI-S score of 2 ('borderline mentally ill'). Although our analysis is based on a large number of patients, the original trials were not specifically designed to examine our research question. The results might contribute to a better understanding and improved interpretation of clinical trial results in MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions.

PubMed

Namour, Florence; Desrivot, Julie; Van der Aa, Annegret; Harrison, Pille; Tasset, Chantal; van't Klooster, Gerben

2016-01-01

The selective Janus kinase 1 inhibitor filgotinib (GLPG0634), which is currently in clinical development for the treatment of rheumatoid arthritis (RA) and Crohn's disease, demonstrated encouraging safety and efficacy profiles in RA patients after 4 weeks of daily dosing. As RA patients might be treated with multiple medications simultaneously, possible drug-drug interactions of filgotinib with cytochrome P450 enzymes and with key drug transporters were evaluated in vitro and in clinical studies. The enzymes involved in filgotinib's metabolism and the potential interactions of the parent and its active major metabolite with drug-metabolizing enzymes and drug transporters, were identified using recombinant enzymes, human microsomes, and cell systems. Furthermore, filgotinib's interaction potential with CYP3A4 was examined in an open-label study in healthy volunteers, which evaluated the impact of filgotinib co-administration on the CYP3A4-sensitive substrate midazolam. The potential interaction with the common RA drug methotrexate was investigated in a clinical study in RA patients. In vitro, filgotinib and its active metabolite at clinically relevant concentrations did not interact with cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, and did not inhibit key drug transporters. In the clinic, a lack of relevant pharmacokinetic drug interactions by filgotinib and its active metabolite with substrates of CYP3A4, as well as with organic anion transporters involved in methotrexate elimination were found. the collective in vivo and in vitro data on drug-metabolizing enzymes and on key drug transporters, support co-administration of filgotinib with commonly used RA drugs to patients without the need for dose adjustments.

Application of basic physics principles to clinical neuroradiology: differentiating artifacts from true pathology on MRI.

PubMed

Hakky, Michael; Pandey, Shilpa; Kwak, Ellie; Jara, Hernan; Erbay, Sami H

2013-08-01

This article outlines artifactual findings commonly encountered in neuroradiologic MRI studies and offers clues to differentiate them from true pathology on the basis of their physical properties. Basic MR physics concepts are used to shed light on the causes of these artifacts. MRI is one of the most commonly used techniques in neuroradiology. Unfortunately, MRI is prone to image distortion and artifacts that can be difficult to identify. Using the provided case illustrations, practical clues, and relevant physical applications, radiologists may devise algorithms to troubleshoot these artifacts.

Muscle-Tendon-Enthesis Unit.

PubMed

Tadros, Anthony S; Huang, Brady K; Pathria, Mini N

2018-07-01

Injuries to the muscle-tendon-enthesis unit are common and a significant source of pain and loss of function. This article focuses on the important anatomical and biomechanical considerations for each component of the muscle-tendon-enthesis unit. We review normal and pathologic conditions affecting this unit, illustrating the imaging appearance of common disorders on magnetic resonance imaging and ultrasound. Knowledge of the anatomy and biomechanics of these structures is crucial for the radiologist to make accurate diagnoses and provide clinically relevant assessments. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids

PubMed Central

Dhanda, Ashwin D; Sinha, Ashish; Hunt, Vicky; Saleem, Sarah; Cramp, Matthew E; Collins, Peter L

2017-01-01

AIM To determine whether infection in patients with acute severe alcoholic hepatitis (AAH) treated with corticosteroids is associated with increased mortality. METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections (body temperature > 38 °C or < 36 °C for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis. RESULTS Seventy-two patients were included in the final analysis (mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15 (21%), 23 (32%) and 31 (43%) at day 28, day 90 and 1 year respectively. 36 (50%) had a clinically relevant infection during their hospitalisation (23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites (31%) and bacteraemia (31%) followed by urinary tract (19%) and respiratory tract (8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia (22%) and Enterococcus (20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality. CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality. PMID:28373772

Plasma amyloid β, depression, and dementia in community-dwelling elderly.

PubMed

Direk, Nese; Schrijvers, Elisabeth M C; de Bruijn, Renée F A G; Mirza, Saira; Hofman, Albert; Ikram, M Arfan; Tiemeier, Henning

2013-04-01

Plasma amyloid β (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, a few clinical studies tested the cross-sectional association of Aβ levels with depression in elderly and showed incongruous findings. Hence, we tested the longitudinal association between Aβ levels and depressive symptoms in community-dwelling elderly. The study is embedded in a population-based cohort of 980 participants aged 60 years or older from the Rotterdam Study with Aβ levels. Participants were evaluated for depressive symptoms with the Centre for Epidemiological Studies-Depression scale at baseline and repeatedly over the mean follow-up of 11 years. We first performed cross-sectional analyses. Then, we tested the longitudinal association between Aβ levels and depressive symptoms after excluding participants with dementia during follow-up. In cross-sectional analyses, persons with high Aβ(1-40) levels had more clinically relevant depressive symptoms. However, this association was accounted for by persons with clinically relevant depressive symptoms who developed dementia within the next 11 years. In longitudinal analyses, persons with low levels of Aβ(1-40) and Aβ(1-42) without dementia had a higher risk of clinically relevant depressive symptoms during the follow-up. These findings suggest that the cross-sectional association between high plasma Aβ levels and clinically relevant depressive symptoms in the elderly is due to prodromal dementia. In contrast, the longitudinal association between low plasma Aβ levels and depressive symptoms could not be explained by dementia during follow-up suggesting that Aβ peptides may play a distinct role on depression etiology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical metabolomics paves the way towards future healthcare strategies

PubMed Central

Collino, Sebastiano; Martin, François‐Pierre J.; Rezzi, Serge

2013-01-01

Metabolomics is recognized as a powerful top‐down system biological approach to understand genetic‐environment‐health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammalian systems with regard to disease aetiology, diagnostic stratification and, potentially, mechanism of action of therapeutic solutions. A key feature of metabolomics lies in its ability to underpin the complex metabolic interactions of the host with its commensal microbial partners providing a new way to define individual and population phenotypes. This review aims at describing recent applications of metabolomics in clinical fields with insight into diseases, diagnostics/monitoring and improvement of homeostatic metabolic regulation. PMID:22348240

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

PubMed

Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Clinical Relevance of Force Platform Measures in Multiple Sclerosis: A Review

PubMed Central

Prosperini, Luca; Pozzilli, Carlo

2013-01-01

Balance impairment and falls are frequent in patients with multiple sclerosis (PwMS), and they may occur even at the earliest stage of the disease and in minimally impaired patients. The introduction of computer-based force platform measures (i.e., static and dynamic posturography) has provided an objective and sensitive tool to document both deficits and improvements in balance. By using more challenging test conditions, force platform measures can also reveal subtle balance disorders undetectable by common clinical scales. Furthermore, posturographic techniques may also allow to reliably identify PwMS who are at risk of accidental falls. Although force platform measures offer several theoretical advantages, only few studies extensively investigated their role in better managing PwMS. Standardised procedures, as well as clinical relevance of changes detected by static or dynamic posturography, are still lacking. In this review, we summarized studies which investigated balance deficit by means of force platform measures, focusing on their ability in detecting patients at high risk of falls and in estimating rehabilitation-induced changes, highlighting the pros and the cons with respect to clinical scales. PMID:23766910

Dissociative absorption: An empirically unique, clinically relevant, dissociative factor.

PubMed

Soffer-Dudek, Nirit; Lassri, Dana; Soffer-Dudek, Nir; Shahar, Golan

2015-11-01

Research of dissociative absorption has raised two questions: (a) Is absorption a unique dissociative factor within a three-factor structure, or a part of one general dissociative factor? Even when three factors are found, the specificity of the absorption factor is questionable. (b) Is absorption implicated in psychopathology? Although commonly viewed as "non-clinical" dissociation, absorption was recently hypothesized to be specifically associated with obsessive-compulsive symptoms. To address these questions, we conducted exploratory and confirmatory factor analyses on 679 undergraduates. Analyses supported the three-factor model, and a "purified" absorption scale was extracted from the original inclusive absorption factor. The purified scale predicted several psychopathology scales. As hypothesized, absorption was a stronger predictor of obsessive-compulsive symptoms than of general psychopathology. In addition, absorption was the only dissociative scale that longitudinally predicted obsessive-compulsive symptoms. We conclude that absorption is a unique and clinically relevant dissociative tendency that is particularly meaningful to obsessive-compulsive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Analytical challenges translating mass spectrometry-based phosphoproteomics from discovery to clinical applications

PubMed Central

Iliuk, Anton B.; Arrington, Justine V.; Tao, Weiguo Andy

2014-01-01

Phosphoproteomics is the systematic study of one of the most common protein modifications in high throughput with the aim of providing detailed information of the control, response, and communication of biological systems in health and disease. Advances in analytical technologies and strategies, in particular the contributions of high-resolution mass spectrometers, efficient enrichments of phosphopeptides, and fast data acquisition and annotation, have catalyzed dramatic expansion of signaling landscapes in multiple systems during the past decade. While phosphoproteomics is an essential inquiry to map high-resolution signaling networks and to find relevant events among the apparently ubiquitous and widespread modifications of proteome, it presents tremendous challenges in separation sciences to translate it from discovery to clinical practice. In this mini-review, we summarize the analytical tools currently utilized for phosphoproteomic analysis (with focus on MS), progresses made on deciphering clinically relevant kinase-substrate networks, MS uses for biomarker discovery and validation, and the potential of phosphoproteomics for disease diagnostics and personalized medicine. PMID:24890697

Nursing journal clubs and the clinical nurse specialist.

PubMed

Westlake, Cheryl; Albert, Nancy M; Rice, Karen L; Bautista, Cynthia; Close, Jackie; Foster, Jan; Timmerman, Gayle M

2015-01-01

The purpose of this article was to describe the clinical nurse specialist's role in developing and implementing a journal club. Tools for critiquing clinical and research articles with an application of each are provided. The journal club provides a forum through which nurses maintain their knowledge base about clinically relevant topics and developments in their specific clinical discipline, analyze and synthesize the relevant scientific literature as evidence, and engage in informal discussions about evidence-based and best practices. The value of journal clubs includes nursing staff education, review of and support for evidence-based practice, promotion of nursing research, and fostering of organization-wide nursing practice changes. The process for establishing a journal club and suggested appraisal tools are discussed. In addition, strategies for overcoming barriers to the implementation of a journal club are outlined. Suggested article review questions and a reporting format for clinical and research articles are provided with examples from 2 articles. Finally, a glossary of terms commonly used by research scientists and manuscript writers are listed and additional resources provided. The clinical nurse specialist's role in developing and implementing a journal club will be facilitated through the use of this article. Enhanced nursing staff education, evidence-based practice, organization-wide nursing practice changes, and nursing research may be conducted following the implementation of a nursing journal club.

Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significa...

[News on hyponatremia].

PubMed

Fenske, Wiebke; Christ-Crain, Mirjam

2016-04-01

Hyponatremia is the most common electrolyte disorder in clinical practice with often severe and devastating complications. Hyponatremia itself as well as its inappropriate management is associated with pronounced morbidity and increased mortality risk. This manuscript presents some relevant novel findings in this field and discusses them in the context of the recently elaborated first European Guideline of hyponatremia. © Georg Thieme Verlag KG Stuttgart · New York.

Benefits of dietary fiber in clinical nutrition.

PubMed

Klosterbuer, Abby; Roughead, Zamzam Fariba; Slavin, Joanne

2011-10-01

Dietary fiber is widely recognized as an important part of a healthy diet and is a common addition to enteral nutrition (EN) formulas. Fiber sources differ in characteristics such as solubility, fermentability, and viscosity, and it is now well known that different types of fiber exert varying physiological effects in the body. Clinical studies suggest fiber can exert a wide range of benefits in areas such as bowel function, gut health, immunity, blood glucose control, and serum lipid levels. Although early clinical nutrition products contained fiber from a single source, it is now thought that blends of fiber from multiple sources more closely resemble a regular diet and may provide a greater range of benefits for the patient. Current recommendations support the use of dietary fiber in clinical nutrition when no contraindications exist, but little information exists about which types and combinations of fibers provide the relevant benefit in certain patient populations. This article summarizes the different types of fiber commonly added to EN products and reviews the current literature on the use of fiber blends in clinical nutrition.

MERALGIA PARESTHETICA: A REVIEW OF THE LITERATURE

PubMed Central

Kolber, Morey J.; Salamh, Paul A.

2013-01-01

Background and Purpose: Meralgia Paresthetica (MP) is a nerve entrapment which may cause pain, paresthesias, and sensory loss within the distribution of the lateral cutaneous nerve of the thigh. When the differential diagnosis of lateral or anterolateral thigh pain is inconclusive, MP should be considered as a potential source. MP produces similar signs and symptoms as those associated with more common diagnoses such as lumbar spine pathology. This clinical commentary will review the most relevant literature on MP with an emphasis on recognition and management of this condition. Description of Topic with Related Evidence: The authors reviewed the most relevant published literature on MP from 1970 to 2013 located using the databases PubMed, CINAHL, and Proquest. Discussion/Relation to Clinical Practice: MP still remains a diagnostic challenge since it can mimic other common diagnoses. Understanding the current literature surrounding the diagnosis and treatment of MP is essential for clinicians practicing in the outpatient environment. The consensus on the most effective non‐surgical and surgical interventions is still limited, as is the research on physical therapy interventions for this condition. Perhaps the lack of research and global consensus represents a knowledge deficit that makes MP a challenge to diagnose and successfully treat. Future collaborative studies are needed to improve the clinical diagnostics and understanding of interventions for this pathology. Level of Evidence: 5 PMID:24377074

Spondyloarthritis, diffuse idiopathic skeletal hyperostosis (DISH) and chondrocalcinosis.

PubMed

Armas, Jácome Brugues; Couto, Ana Rita; Bettencourt, Bruno Filipe

2009-01-01

The authors describe the main clinical and radiological findings of common enthesopathic disorders-spondylarthritis (SpA), chondrocalcinosis/calcium pyrophosphate dehydrate crystal deposition disease (CPPD CDD) and diffuse idiopathic skeletal hyperostosis (DISH), stressing similarities and differences which may help in the differential diagnosis. They emphasize the clinical presentation of the "pseudoankylosing spondylitis" forms of CPPD CDD. They also review the most relevant genes and molecular mechanisms associated with these conditions and with another enthesopathic disorder with high prevalence in the Japanese population-ossification of the posterior longitudinal ligament (OPLL).

Bipolar disorder and ADHD: comorbidity and diagnostic distinctions.

PubMed

Marangoni, Ciro; De Chiara, Lavinia; Faedda, Gianni L

2015-08-01

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) are neurodevelopmental disorders with onset in childhood and early adolescence, and common persistence in adulthood. Both disorders are often undiagnosed, misdiagnosed, and sometimes over diagnosed, leading to high rates of morbidity and disability. The differentiation of these conditions is based on their clinical features, comorbidity, psychiatric family history course of illness, and response to treatment. We review recent relevant findings and highlight epidemiological, clinical, family history, course, and treatment-response differences that can aid the differential diagnosis of these conditions in an outpatient pediatric setting.

Mental health and substance abuse characteristics among a clinical sample of urban American Indian/Alaska native youths in a large California metropolitan area: a descriptive study.

PubMed

Dickerson, Daniel L; Johnson, Carrie L

2012-02-01

This study analyzes descriptive data among a clinical sample of American Indian/Alaska Native (AI/AN) youths receiving mental health services in a large California metropolitan area. Among 118 urban AI/AN youths, mood disorders (41.5%) and adjustment disorder (35.4%) were the most common mental health diagnoses. Alcohol (69.2%) and marijuana (50.0%) were the most commonly used substances. Witnessing domestic violence (84.2%) and living with someone who had a substance abuse problem (64.7%) were reported. The majority of patients demonstrated various behavior and emotional problems. Enhancing culturally relevant mental health and substance abuse treatment and prevention programs for urban AI/AN youth is suggested.

Renal incidental findings on computed tomography

PubMed Central

Meyer, Hans Jonas; Pfeil, Alina; Schramm, Dominik; Bach, Andreas Gunter; Surov, Alexey

2017-01-01

Abstract Renal incidental findings (IFs) are common. However, previous reports investigated renal IFs were limited to patient selection. The purpose of this study was to estimate the prevalence and distribution of all renal IFs on computed tomography (CT) in a large patient collective. All patients, who underwent CT investigations of the abdominal region at our institution in the time period between January 2006 and February 2014 were included in this study. Inclusion criteria were as follows: no previous history of renal diseases and well image quality. Patients with known kidney disorders were excluded from the study. Overall, 7365 patients meet the inclusion criteria were identified. There were 2924 (39.7%) women and 4441 men (60.3%) with a mean age of 59.8 ± 16.7 years. All CTs were retrospectively analyzed in consensus by 2 radiologists. Collected data were evaluated by means of descriptive statistics. Overall, 2756 patients (37.42% of all included patients) showed 3425 different renal IFs (1.24 findings per patient). Of all renal IFs, 123 (3.6%) findings were clinically relevant, 259 (7.6%) were categorized as possibly clinically relevant, and 3043 (88.8%) were clinically non relevant. Different renal IFs can be detected on CT. The present study provides a real prevalence and proportion of them in daily clinical routine. Kidneys should be thoroughly evaluated because of the fact that incidental renal findings occur frequently. PMID:28658098

Mechanisms for pattern specificity of deep-brain stimulation in Parkinson’s disease

PubMed Central

Mato, Germán; Dellavale, Damián

2017-01-01

Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network. In this work, it is shown that the clinically relevant range for both, the frequency and intensity of the electrical stimulation pattern, is an emergent property of the BG anatomy at the system-level that can be addressed using mean-field descriptive models of the BG network. Moreover, it is shown that the activity resetting mechanism elicited by electrical stimulation provides a natural explanation to the ineffectiveness of irregular (i.e., aperiodic) stimulation patterns, which has been commonly observed in previously reported pathophysiology models of Parkinson’s disease. Using analytical and numerical techniques, these results have been reproduced in both cases: 1) a reduced mean-field model that can be thought as an elementary building block capable to capture the underlying fundamentals of the relevant loops constituting the BG-thalamocortical network, and 2) a detailed model constituted by the direct and hyperdirect loops including one-dimensional spatial structure of the BG nuclei. We found that the optimal ranges for the essential parameters of the stimulation patterns can be understood without taking into account biophysical details of the relevant structures. PMID:28813460

Health determining concepts important to people with Crohn's disease and their coverage by patient-reported outcomes of health and wellbeing☆☆☆

PubMed Central

Dür, Mona; Sadloňová, Martina; Haider, Stefanie; Binder, Alexa; Stoffer, Michaela; Coenen, Michaela; Smolen, Josef; Dejaco, Clemens; Kautzky-Willer, Alexandra; Fialka-Moser, Veronika; Moser, Gabriele; Stamm, Tanja Alexandra

2014-01-01

Background and aims Busy clinical settings often restrict the possibility to focus on concepts that determine health in a positive way, commonly assessed by using patient-reported outcomes (PROs). We aimed to explore which determinants of health (DHs) are important to people with Crohn's disease (CD), to understand possible gender differences and to analyze whether these DHs are covered by PROs used in CD. Methods Two systematic literature reviews were done to identify relevant DHs and clinically relevant PROs. We conducted a qualitative narrative biographical study and mapped the patients' experiences to concepts that determine health in a positive way. Experiences, DHs and the items of the PROs were compared by the WHO International Classification of Functioning, Disability and Health (ICF) as a common framework. Results 15 people with CD with a median age of 46 years (IQR 34–60) and median disease duration of 15 years (IQR 8–30) participated. Self-efficacy, social support, job satisfaction and occupational balance were mentioned most frequently. While participation appeared to have greater meaning to men, appreciation and resilience seemed to be more important for women. Of 18 PROs the Perceived Stress Questionnaire (PSQ), the Inflammatory Bowel disease — Self-efficacy scale (IBD-SES), the Life Orientation Test — Revised (LOT-R) and the Patient Activation Measure 13 (PAM-13) cover most DHs. Conclusions This is the first study elaborating the coverage of patient's perspective by commonly used PROs in CD. The findings could support health professionals to focus on DHs in people with CD in clinical practice and research. PMID:23375212

Is ginger beneficial for nausea and vomiting? An update of the literature.

PubMed

Marx, Wolfgang; Kiss, Nicole; Isenring, Liz

2015-06-01

Nausea and vomiting can pose a significant burden to patients in a variety of clinical settings. Previous evidence suggests that ginger may be an effective treatment for these symptoms; however, current evidence has been mixed. This article discusses recent clinical trials that have investigated ginger as a treatment for multiple types of nausea and vomiting. In addition, the potential mechanisms of action of ginger will be discussed. This article identified nine studies and seven reviews that investigated ginger for morning sickness, postoperative nausea and vomiting, chemotherapy-induced, and antiretroviral-induced nausea and vomiting. All studies reported that ginger provided a significant reduction in nausea and vomiting; however, the clinical relevance of some studies is less certain. Common limitations within the literature include the lack of standardized extracts, poorly controlled or blinded studies, and limited sample size. In addition, recent evidence has provided further support for 5-HT3 receptor antagonism as a mechanism by which ginger may exert its potentially beneficial effect on nausea and vomiting. The results of studies in this article suggest that ginger is a promising treatment for nausea and vomiting in a variety of clinical settings and possesses a clinically relevant mechanism. However, further studies are required to address the limitations in the current clinical literature before firm recommendations for its use can be made.

Translating Research on Myoelectric Control into Clinics-Are the Performance Assessment Methods Adequate?

PubMed

Vujaklija, Ivan; Roche, Aidan D; Hasenoehrl, Timothy; Sturma, Agnes; Amsuess, Sebastian; Farina, Dario; Aszmann, Oskar C

2017-01-01

Missing an upper limb dramatically impairs daily-life activities. Efforts in overcoming the issues arising from this disability have been made in both academia and industry, although their clinical outcome is still limited. Translation of prosthetic research into clinics has been challenging because of the difficulties in meeting the necessary requirements of the market. In this perspective article, we suggest that one relevant factor determining the relatively small clinical impact of myocontrol algorithms for upper limb prostheses is the limit of commonly used laboratory performance metrics. The laboratory conditions, in which the majority of the solutions are being evaluated, fail to sufficiently replicate real-life challenges. We qualitatively support this argument with representative data from seven transradial amputees. Their ability to control a myoelectric prosthesis was tested by measuring the accuracy of offline EMG signal classification, as a typical laboratory performance metrics, as well as by clinical scores when performing standard tests of daily living. Despite all subjects reaching relatively high classification accuracy offline, their clinical scores varied greatly and were not strongly predicted by classification accuracy. We therefore support the suggestion to test myocontrol systems using clinical tests on amputees, fully fitted with sockets and prostheses highly resembling the systems they would use in daily living, as evaluation benchmark. Agreement on this level of testing for systems developed in research laboratories would facilitate clinically relevant progresses in this field.

A Primer on Foraging and the Explore/Exploit Trade-Off for Psychiatry Research.

PubMed

Addicott, M A; Pearson, J M; Sweitzer, M M; Barack, D L; Platt, M L

2017-09-01

Foraging is a fundamental behavior, and many types of animals appear to have solved foraging problems using a shared set of mechanisms. Perhaps the most common foraging problem is the choice between exploiting a familiar option for a known reward and exploring unfamiliar options for unknown rewards-the so-called explore/exploit trade-off. This trade-off has been studied extensively in behavioral ecology and computational neuroscience, but is relatively new to the field of psychiatry. Explore/exploit paradigms can offer psychiatry research a new approach to studying motivation, outcome valuation, and effort-related processes, which are disrupted in many mental and emotional disorders. In addition, the explore/exploit trade-off encompasses elements of risk-taking and impulsivity-common behaviors in psychiatric disorders-and provides a novel framework for understanding these behaviors within an ecological context. Here we explain relevant concepts and some common paradigms used to measure explore/exploit decisions in the laboratory, review clinically relevant research on the neurobiology and neuroanatomy of explore/exploit decision making, and discuss how computational psychiatry can benefit from foraging theory.

Establishing Common Cost Measures to Evaluate the Economic Value of Patient Navigation Programs

PubMed Central

Whitley, Elizabeth; Valverde, Patricia; Wells, Kristen; Williams, Loretta; Teschner, Taylor; Shih, Ya-Chen Tina

2011-01-01

Background Patient navigation is an intervention aimed at reducing barriers to healthcare for underserved populations as a means to reduce cancer health disparities. Despite the proliferation of patient navigation programs across the United States, information related to the economic impact and sustainability of these programs is lacking. Method Following a review of the relevant literature, the Health Services Research (HSR) cost workgroup of the American Cancer Society National Patient Navigator Leadership Summit met to examine cost data relevant to assessing the economic impact of patient navigation and to propose common cost metrics. Results Recognizing that resources available for data collection, management and analysis vary, five categories of core and optional cost measures were identified related to patient navigator programs, including, program costs, human capital costs, direct medical costs, direct non-medical costs and indirect costs. Conclusion(s) Information demonstrating economic as well as clinical value is necessary to make decisions about sustainability of patient navigation programs. Adoption of these common cost metrics are recommended to promote understanding of the economic impact of patient navigation and comparability across diverse patient navigation programs. PMID:21780096

Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

PubMed

Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

2011-12-01

Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Is combining metronidazole and alcohol really hazardous?].

PubMed

Fjeld, Hilde; Raknes, Guttorm

2014-09-16

It is common practice to warn against intake of alcohol (ethanol) when taking metronidazole because of the risk of an effect similar to disulfiram (Antabuse). In this article we investigate whether such a warning has any real basis. KNOWLEDGE BASE: The article is based on a review of relevant literature retrieved through a search in PubMed. A search was also made in the WHO's database on adverse effects. No in-vitro studies, animal models, reports of adverse effects or clinical studies provide any convincing evidence of a disulfiram-like interaction between ethanol and metronidazole. The warning against simultaneous use of alcohol and metronidazole appear to be based on laboratory experiments and individual case histories in which the reported reactions are equally likely to have been caused by ethanol alone or by adverse effects of metronidazole. Recent research does not confirm a clinically relevant interaction between ethanol and metronidazole.

Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

PubMed

Grady, Haiyan; Elder, David; Webster, Gregory K; Mao, Yun; Lin, Yiqing; Flanagan, Talia; Mann, James; Blanchard, Andy; Cohen, Michael J; Lin, Judy; Kesisoglou, Filippos; Hermans, Andre; Abend, Andreas; Zhang, Limin; Curran, David

2018-01-01

This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades, dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle. The definitions of commonly used dissolution approaches, how they relate to one another and how they may be applied in modern drug development, and life cycle management is described in this article. Specifically, this article discusses the purpose, advantages, and limitations of quality control, biorelevant, and clinically relevant dissolution methods. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa

PubMed Central

Baker, J L; Shriner, D; Bentley, A R; Rotimi, C N

2017-01-01

As the common birthplace of all human populations, modern humans have lived longer on the African continent than in any other geographical region of the world. This long history, along with the evolutionary need to adapt to environmental challenges such as exposure to infectious agents, has led to greater genetic variation in Africans. The vast genetic variation in Africans also extends to genes involved in the absorption, distribution, metabolism and excretion of pharmaceuticals. Ongoing cataloging of these clinically relevant variants reveals huge allele-frequency differences within and between African populations. Here, we examine Africa's large burden of infectious disease, discuss key examples of known genetic variation modulating disease risk, and provide examples of clinically relevant variants critical for establishing dosing guidelines. We propose that a more systematic characterization of the genetic diversity of African ancestry populations is required if the current benefits of precision medicine are to be extended to these populations. PMID:27779243

Learning clinical reasoning.

PubMed

Pinnock, Ralph; Welch, Paul

2014-04-01

Errors in clinical reasoning continue to account for significant morbidity and mortality, despite evidence-based guidelines and improved technology. Experts in clinical reasoning often use unconscious cognitive processes that they are not aware of unless they explain how they are thinking. Understanding the intuitive and analytical thinking processes provides a guide for instruction. How knowledge is stored is critical to expertise in clinical reasoning. Curricula should be designed so that trainees store knowledge in a way that is clinically relevant. Competence in clinical reasoning is acquired by supervised practice with effective feedback. Clinicians must recognise the common errors in clinical reasoning and how to avoid them. Trainees can learn clinical reasoning effectively in everyday practice if teachers provide guidance on the cognitive processes involved in making diagnostic decisions. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Environmental contact factors in eczema and the results of patch testing Chinese patients with a modified European standard series of allergens.

PubMed

Li, Lin-Feng; Guo, Jing; Wang, Jing

2004-07-01

Environmental contact factors in eczema were investigated in China by clinical questionnaire and patch testing patients with a modified European standard series of allergens. 217 consecutive eczema patients were studied. Contact dermatitis (CD) was clinically diagnosed in 30% of the patients. Among the patients patch tested, 46 patients had clinically diagnosed allergic CD (ACD), 20 patients clinically had non-ACD (NACD) (including 16 cases of irritant contact dermatitis, 1 case of phototoxic contact reaction and 3 cases of asteatotic eczema) and 115 patients had clinically suspected ACD. 45 patients (98%) in the ACD group went on to have relevant patch test results. The most common ACD was from metals, fragrance materials, cosmetics and rubber materials. The most common contact allergens identified were nickel, fragrance mix, para-phenylenediamine (PPD), carba mix and thimerosal. No adverse reactions were observed to patch testing, except for pruritus in patch-test-positive patients. The positive rate of patch testing in ACD was much higher than that in NACD (98% versus 15%, P < 0.05, chi(2)-test). 60 (28%) patients had facial dermatitis (FD). Among these, 20 (33%) were confirmed as having ACD. 48 (22%) patients had hand dermatitis (HD). Among these, 7 (15%) were confirmed as having ACD. Fewer patients were confirmed as having ACD in the HD group than in the FD (15% versus 33%, P < 0.05, chi(2)-test). Although the difference was not significant, the total positivity rate in the HD group (55%) was lower than in the other groups. 65 (30%) patients had unclassified endogenous eczema (UEE). The total positive rate of patch testing in the UEE group (56%) was no different from that in the FD or HD groups. However, the relevance of positive patch tests was hard to determine in UEE. These results indicate that CD is common in eczema; relatively more patients with FD have ACD, while other factors, such as irritation, may play more of a role in HD. The total positive rate of patch testing in the UEE group was no different from that in the FD or HD groups, suggesting that patch testing should be stressed in UEE and the relevance of positive patch test results in UEE should be studied further. It is effective and safe to patch eczema patients with a modified European standard series of allergens in China.

A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry?

PubMed

Bushe, Chris J; Bradley, Andrew; Pendlebury, John

2010-07-01

Hyperprolactinaemia is a common adverse event reported in association with treatments used in schizophrenia and bipolar disorder. Recent data are suggestive that hyperprolactinaemia may have a range of significant short-and long-term clinical consequences. The objective of this review is to examine the causes, frequency and clinical consequences of hyperprolactinaemia in the severely mentally ill (SMI) with a focus on patients taking antipsychotic medications. A Medline search was carried out to identify relevant publications. Reference lists from previous review articles were also examined to search for additional data. Hyperprolactinaemia may be one of the most common adverse events associated with some antipsychotic medications. Precise rates with individual drugs had however until recently been poorly categorized. The relationship between hyperprolactinaemia and adverse outcomes in the SMI population appears similar to that in the general population. Adverse outcomes (such as sexual dysfunction) can occur acutely and in the longer term (bone fractures and possibly breast cancer), but the precise link between degree and length of hyperprolactinaemia and adverse outcome remains to be established. In conclusion, hyperprolactinaemia is a common treatment-emergent adverse event of some antipsychotic medications and may have clinical consequences. Physicians must balance the benefits and risks of treatment when determining appropriate therapy for individual patients.

Pulmonary atelectasis in newborns with clinically treatable diseases who are on mechanical ventilation: clinical and radiological aspects

PubMed Central

Dominguez, Mariana Chiaradia; Alvares, Beatriz Regina

2018-01-01

Objective To analyze the radiological aspects of pulmonary atelectasis in newborns on mechanical ventilation and treated in an intensive care unit, associating the characteristics of atelectasis with the positioning of the head and endotracheal tube seen on the chest X-ray, as well as with the clinical variables. Materials and Methods This was a retrospective cross-sectional study of 60 newborns treated between 1985 and 2015. Data were collected from medical records and radiology reports. To identify associations between variables, we used Fisher's exact test. The level of significance was set at p < 0.05. Results The clinical characteristics associated with improper positioning of the endotracheal tube were prematurity and a birth weight of less than 1000 g. Among the newborns evaluated, the most common comorbidity was hyaline membrane disease. Atelectasis was seen most frequently in the right upper lobe, although cases of total atelectasis were more common in the left lung. Malpositioning of the head showed a trend toward an association with atelectasis in the left upper lobe. Conclusion Pulmonary atelectasis is a common complication in newborns on mechanical ventilation. Radiological evaluation of the endotracheal tube placement provides relevant information for the early correction of this condition. PMID:29559762

New daily persistent headache in the paediatric population.

PubMed

Kung, E; Tepper, S J; Rapoport, A M; Sheftell, F D; Bigal, M E

2009-01-01

We conducted a clinic-based study focusing on the clinical features of new-onset chronic daily headaches (CDH) in children and adolescents. The clinical records and headache diaries of 306 children and adolescents were reviewed, to identify 187 with CDH. Relevant information was transferred to a standardized form that included operational criteria for the diagnoses of the headaches. Since we were interested in describing the clinical features of these headaches, we followed the criteria A and B of the 2nd edn of the International Classification of Headache Disorders (ICHD-2) and refer to them as new daily persistent headaches (NDPH) regardless of the presence of migraine features (therefore, this is a modified version of the ICHD-2 criteria). From the 56 adolescents with NDPH, most (91.8%) did not overuse medications. Nearly half (48.1%) reported they could recall the month when their headaches started. NDPH was more common than chronic tension-type headache in both adolescents overusing and not overusing medication. Individuals with NDPH had headaches fulfilling criteria for migraine on an average of 18.5 days per month. On most days, they had migraine-associated symptoms (one of nausea, photophobia or phonophobia)). NDPH is common in children and adolescents with CDH. Most subjects do not overuse medication. Migraine features are common.

[Depression and epilepsy : Two clinical pictures with common causes?].

PubMed

Borgmann, M; Holtkamp, M; Adli, M; Behr, J

2016-07-01

Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research.

PubMed

Kempf, Emmanuelle; Bogaerts, Jan; Lacombe, Denis; Liu, Lifang

2017-11-01

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Review of Atomoxetine Effects in Young People with Developmental Disabilities

PubMed Central

Aman, Michael G.; Smith, Tristram; Arnold, L. Eugene; Corbett-Dick, Patricia; Rameshwari.Tumuluru; Hollway, Jill A.; Hyman, Susan L.; Mendoza-Burchamm, Marissa; Pan, Xueliang; Mruzek, Daniel W.; Lecavalier, Luc; Levato, Lynne; Silverman, Laura B.; Handen, Benjamin

2014-01-01

This review summarizes the pharmacokinetic characteristics, pharmacodynamic properties, common side effects, and clinical advantages and disadvantages associated with atomoxetine (ATX) treatment in typically developing children and adults with ADHD. Then the clinical research to date in developmental disabilities (DD), including autism spectrum disorders (ASD), is summarized and reviewed. Of the 11 relevant reports available, only two were placebo-controlled randomized clinical trials, and both focused on a single DD population (ASD). All trials but one indicated clinical improvement in ADHD symptoms with ATX, although it was difficult to judge the magnitude and validity of reported improvement in the absence of placebo controls. Effects of ATX on co-occurring behavioral and cognitive symptoms were much less consistent. Appetite decrease, nausea, and irritability were the most common adverse events reported among children with DD; clinicians should be aware that, as with stimulants, irritability appears to occur much more commonly in persons with DD than in typically developing individuals. Splitting the dose initially, starting below the recommended starting dose, and titrating slowly may prevent or ameliorate side effects. Patience is needed for the slow build-up of benefit. Conclusions: ATX holds promise for managing ADHD symptoms in DD, but properly controlled, randomized clinical trials of atomoxetine in intellectual disability and ASD are sorely needed. Clinicians and researchers should be vigilant for emergence of irritability with ATX treatment. Effects of ATX on cognition in DD are virtually unstudied. PMID:24732041

Linguistic Adaptation of the Clinical Dementia Rating Scale for a Spanish-Speaking Population

PubMed Central

Oquendo-Jiménez, Ilia; Mena, Rafaela; Antoun, Mikhail D.; Wojna, Valerie

2012-01-01

Background Alzheimer's disease (AD) is the most common form of dementia worldwide. In Hispanic populations there are few validated tests for the accurate identification and diagnosis of AD. The Clinical Dementia Rating (CDR) scale is an internationally recognized questionnaire used to stage dementia. This study's objective was to develop a linguistic adaptation of the CDR for the Puerto Rican population. Methods The linguistic adaptation consisted of the evaluation of each CDR question (item) and the questionnaire's instructions, for similarities in meaning (semantic equivalence), relevance of content (content equivalence), and appropriateness of the questionnaire's format and measuring technique (technical equivalence). A focus group methodology was used to assess cultural relevance, clarity, and suitability of the measuring technique in the Argentinean version of the CDR for use in a Puerto Rican population. Results A total of 27 semantic equivalence changes were recommended in four categories: higher than 6th grade level of reading, meaning, common use, and word preference. Four content equivalence changes were identified, all focused on improving the applicability of the test questions to the general population's concept of street addresses and common dietary choices. There were no recommendations for changes in the assessment of technical equivalence. Conclusions We developed a linguistically adapted CDR instrument for the Puerto Rican population, preserving the semantic, content, and technical equivalences of the original version. Further studies are needed to validate the CDR instrument with the staging of Alzheimer's disease in the Puerto Rican population. PMID:20496524

A Narrative Review of Lumbar Fusion Surgery With Relevance to Chiropractic Practice.

PubMed

Daniels, Clinton J; Wakefield, Pamela J; Bub, Glenn A; Toombs, James D

2016-12-01

The purpose of this narrative review was to describe the most common spinal fusion surgical procedures, address the clinical indications for lumbar fusion in degeneration cases, identify potential complications, and discuss their relevance to chiropractic management of patients after surgical fusion. The PubMed database was searched from the beginning of the record through March 31, 2015, for English language articles related to lumbar fusion or arthrodesis or both and their incidence, procedures, complications, and postoperative chiropractic cases. Articles were retrieved and evaluated for relevance. The bibliographies of selected articles were also reviewed. The most typical lumbar fusion procedures are posterior lumbar interbody fusion, anterior lumbar interbody fusion, transforaminal interbody fusion, and lateral lumbar interbody fusion. Fair level evidence supports lumbar fusion procedures for degenerative spondylolisthesis with instability and for intractable low back pain that has failed conservative care. Complications and development of chronic pain after surgery is common, and these patients frequently present to chiropractic physicians. Several reports describe the potential benefit of chiropractic management with spinal manipulation, flexion-distraction manipulation, and manipulation under anesthesia for postfusion low back pain. There are no published experimental studies related specifically to chiropractic care of postfusion low back pain. This article describes the indications for fusion, common surgical practice, potential complications, and relevant published chiropractic literature. This review includes 10 cases that showed positive benefits from chiropractic manipulation, flexion-distraction, and/or manipulation under anesthesia for postfusion lumbar pain. Chiropractic care may have a role in helping patients in pain who have undergone lumbar fusion surgery.

Rare Variation in TET2 Is Associated with Clinically Relevant Prostate Carcinoma in African-Americans

PubMed Central

Koboldt, Daniel C.; Kanchi, Krishna L.; Gui, Bin; Larson, David E.; Fulton, Robert S.; Isaacs, William B.; Kraja, Aldi; Borecki, Ingrid B.; Jia, Li; Wilson, Richard K.; Mardis, Elaine R.; Kibel, Adam S.

2016-01-01

Background Common variants have been associated with prostate cancer risk. Unfortunately, few are reproducibly linked to aggressive disease, the phenotype of greatest clinical relevance. One possible explanation is that rare genetic variants underlie a significant proportion of the risk for aggressive disease. Method To identify such variants, we performed a two staged approach using whole exome sequencing followed by targeted sequencing of 800 genes in 652 aggressive prostate cancer patients and 752 disease-free controls in both African and European Americans. In each population, we tested rare variants for association using two gene-based aggregation tests. We established a study-wide significance threshold of 3.125 × 10−5 to correct for multiple testing. Results TET2 in African-Americans was associated with aggressive disease with 24.4% of cases harboring a rare deleterious variant compared to 9.6% of controls (FET p = 1.84×10−5, OR=3.0; SKAT-O p= 2.74×10−5). We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6. Finally, we observed an excess of rare truncation variants in 5 genes including the DNA repair genes MSH6, BRCA1 and BRCA2. This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer. Conclusion Our findings suggest that rare variants influence risk of clinically relevant prostate cancer and, if validated, could serve to identify men for screening, prophylaxis and treatment. Impact This study provides evidence that rare variants in TET2 may help identify African-American men at increased risk for clinically relevant prostate cancer. PMID:27486019

Multiparametric MRI of Prostate Cancer: An Update on State-of-the-Art Techniques and Their Performance in Detecting and Localizing Prostate Cancer

PubMed Central

Hegde, John V.; Mulkern, Robert V.; Panych, Lawrence P.; Fennessy, Fiona M.; Fedorov, Andriy; Maier, Stephan E.; Tempany, Clare M.C.

2013-01-01

Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. PMID:23606141

Corynebacterium Prosthetic Joint Infection

PubMed Central

Cazanave, Charles; Greenwood-Quaintance, Kerryl E.; Hanssen, Arlen D.

2012-01-01

Identification of Corynebacterium species may be challenging. Corynebacterium species are occasional causes of prosthetic joint infection (PJI), but few data are available on the subject. Based on the literature, C. amycolatum, C. aurimucosum, C. jeikeium, and C. striatum are the most common Corynebacterium species that cause PJI. We designed a rapid PCR assay to detect the most common human Corynebacterium species, with a specific focus on PJI. A polyphosphate kinase gene identified using whole-genome sequence was targeted. The assay differentiates the antibiotic-resistant species C. jeikeium and C. urealyticum from other species in a single assay. The assay was applied to a collection of human Corynebacterium isolates from multiple clinical sources, and clinically relevant species were detected. The assay was then tested on Corynebacterium isolates specifically associated with PJI; all were detected. We also describe the first case of C. simulans PJI. PMID:22337986

Rheumatic effects of vibration at work

PubMed Central

Palmer, Keith T; Bovenzi, Massimo

2016-01-01

Occupational exposures to vibration come in many guises and are very common at a population level. It follows that an important minority of working-aged patients seen by medical services will have been exposed to this hazard of employment. Vibration can cause human health effects which may manifest in the patients that rheumatologists see. In this chapter we identify the health effects of relevance to them, and review their epidemiology, pathophysiology, clinical presentation, differential diagnosis, and vocational and clinical management. On either side of this, we describe the nature and assessment of the hazard, the scale and common patterns of exposure to vibration in the community, and the legal basis for controlling health risks, and comment on the role of health surveillance in detecting early adverse effects and what can be done to prevent the rheumatic effects of vibration at work. PMID:26612239

The wisdom of the commons: ensemble tree classifiers for prostate cancer prognosis.

PubMed

Koziol, James A; Feng, Anne C; Jia, Zhenyu; Wang, Yipeng; Goodison, Seven; McClelland, Michael; Mercola, Dan

2009-01-01

Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors.

One Small Step for the Gram Stain, One Giant Leap for Clinical Microbiology

PubMed Central

2016-01-01

The Gram stain is one of the most commonly performed tests in the clinical microbiology laboratory, yet it is poorly controlled and lacks standardization. It was once the best rapid test in microbiology, but it is no longer trusted by many clinicians. The publication by Samuel et al. (J. Clin. Microbiol. 54:1442–1447, 2016, http://dx.doi.org/10.1128/JCM.03066-15) is a start for those who want to evaluate and improve Gram stain performance. In an age of emerging rapid molecular results, is the Gram stain still relevant? How should clinical microbiologists respond to the call to reduce Gram stain error rates? PMID:27008876

Clinical relevance of the utilization of vital Lugol's iodine staining in detection and diagnosis of oral cancer and dysplasia.

PubMed

Elimairi, Imad; Altay, Mehmet Ali; Abdoun, Omer; Elimairi, Amr; Tozoglu, Sinan; Baur, Dale A; Quereshy, Faisal

2017-03-01

The aim of this study is to assess the clinical relevance of the utilization of vital Lugol's iodine staining in detection of oral cancer and dysplastic lesions as well as demarcation of the extent of these lesions. A prospective, cross-sectional, hospital-based study was performed in Khartoum Teaching Dental Hospital, Sudan. Suspicious oral epithelial lesions indicating incisional biopsy were stained with 10 % Lugol's iodine solution and were clinically designated as "negative" for dysplasia or neoplasia when no unstained lesion (USL) area was observed, or as "positive" when a USL area is observed. Incisional biopsies involving both the unstained portion and the stained portion were obtained and histologically evaluated for definitive diagnosis. Forty-five biopsies were obtained from 28 patients. Histopathological examination of the specimens confirmed some degree of dysplasia or neoplasia in all clinically positive specimens with oral squamous cell carcinoma (OSCC) being the most common definitive diagnosis (17 patients, 60.7 %). Clinical relevance level of vital Lugol's iodine staining in detecting oral cancer and dysplasia was found to be 90.9 % (SE = 0.05, P = 0.05). The findings of this study showed that Lugol's iodine is an easy, safe, and effective method of visualizing oral epithelial lesions and differentiating epithelial carcinoma and dysplasia from other benign mucosal lesions. Despite certain limitations, its use is of great value in detection and diagnosis of oral cancer and dysplasia. Lugol's iodine staining can effectively be used in detection of the dysplastic and malignant superficial lesions of the oral epithelium.

Mitochondrial Disorders of DNA Polymerase γ Dysfunction

PubMed Central

Zhang, Linsheng; Chan, Sherine S. L.; Wolff, Daynna J.

2011-01-01

Context Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis. Objectives To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes. Data Sources Review of pertinent published literature and relevant Internet databases. Conclusions Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis. PMID:21732785

Post hoc analyses: after the facts.

PubMed

Srinivas, Titte R; Ho, Bing; Kang, Joseph; Kaplan, Bruce

2015-01-01

Prospective clinical trials are constructed with high levels of internal validity. Sample size and power considerations usually address primary endpoints. Primary endpoints have traditionally included events that are becoming increasingly less common and thus have led to growing use of composite endpoints and noninferiority trial designs in transplantation. This approach may mask real clinical benefit in one or the other domain with regard to either clinically relevant secondary endpoints or other unexpected findings. In addition, endpoints solely chosen based on power considerations are prone to misjudgment of actual treatment effect size as well as consistency of that effect. In the instances where treatment effects may have been underestimated, valuable information may be lost if buried within a composite endpoint. In all these cases, analyses and post hoc analyses of data become relevant in informing practitioners about clinical benefits or safety signals that may not be captured by the primary endpoint. On the other hand, there are many pitfalls in using post hoc determined endpoints. This short review is meant to allow readers to appreciate post hoc analysis not as an entity with a single approach, but rather as an analysis with unique limitations and strengths that often raise new questions to be addressed in further inquiries.

Lung ultrasound compared with chest X-ray in diagnosing postoperative pulmonary complications following cardiothoracic surgery: a prospective observational study.

PubMed

Touw, H R; Parlevliet, K L; Beerepoot, M; Schober, P; Vonk, A; Twisk, J W; Elbers, P W; Boer, C; Tuinman, P R

2018-03-12

Postoperative pulmonary complications are common after cardiothoracic surgery and are associated with adverse outcomes. The ability to detect postoperative pulmonary complications using chest X-rays is limited, and this technique requires radiation exposure. Little is known about the diagnostic accuracy of lung ultrasound for the detection of postoperative pulmonary complications after cardiothoracic surgery, and we therefore aimed to compare lung ultrasound with chest X-ray to detect postoperative pulmonary complications in this group of patients. We performed this prospective, observational, single-centre study in a tertiary intensive care unit treating adult patients who had undergone cardiothoracic surgery. We recorded chest X-ray findings upon admission and on postoperative days 2 and 3, as well as rates of postoperative pulmonary complications and clinically-relevant postoperative pulmonary complications that required therapy according to the treating physician as part of their standard clinical practice. Lung ultrasound was performed by an independent researcher at the time of chest X-ray. We compared lung ultrasound with chest X-ray for the detection of postoperative pulmonary complications and clinically-relevant postoperative pulmonary complications. We also assessed inter-observer agreement for lung ultrasound, and the time to perform both imaging techniques. Subgroup analyses were performed to compare the time to detection of clinically-relevant postoperative pulmonary complications by both modalities. We recruited a total of 177 patients in whom both lung ultrasound and chest X-ray imaging were performed. Lung ultrasound identified 159 (90%) postoperative pulmonary complications on the day of admission compared with 107 (61%) identified with chest X-ray (p < 0.001). Lung ultrasound identified 11 out of 17 patients (65%) and chest X-ray 7 out of 17 patients (41%) with clinically-relevant postoperative pulmonary complications (p < 0.001). The clinically-relevant postoperative pulmonary complications were detected earlier using lung ultrasound compared with chest X-ray (p = 0.024). Overall inter-observer agreement for lung ultrasound was excellent (κ = 0.907, p < 0.001). Following cardiothoracic surgery, lung ultrasound detected more postoperative pulmonary complications and clinically-relevant postoperative pulmonary complications than chest X-ray, and at an earlier time-point. Our results suggest lung ultrasound may be used as the primary imaging technique to search for postoperative pulmonary complications after cardiothoracic surgery, and will enhance bedside decision making. © 2018 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland.

Percussion use and training: a survey of music therapy clinicians.

PubMed

Scheffel, Stephanie; Matney, Bill

2014-01-01

Percussion instruments are commonly used in music therapy practice; however, the body of published literature regarding music therapy-related percussion training and practice is limited. The purpose of our survey study was to describe: (a) clinician perspectives of their academic percussion training; (b) use of percussion testing during academic training; (c) clinician perspectives on relevance, adequacy, and importance of academic percussion training; (d) clinician perspectives of their nonacademic percussion training; and (e) current use of percussion in clinical practice. Through comparisons of these parameters, we sought to provide information that may inform future percussion use and training. Participants were selected using an email list from the Certification Board for Music Therapists. Board-certified music therapists (MT-BC) were provided with a researcher-created survey about academic percussion training, nonacademic percussion training, and use of percussion in clinical practice. Survey response rate was 14.4% (611/4234). We used demographic data to address potential nonresponse error and ensure population representation for region of residence and region of academic training. Results revealed concerns about perceived adequacy of percussion training received during music therapy education (14.6% reported receiving no academic percussion training; 40.6% reported training was not adequate), and absence of percussion-specific proficiency exams. Of the training received, 62.8% indicated that training was relevant; however, a majority (76.5%) recommended current music therapy students receive more percussion training on instruments and skills most relevant to clinical practice. Comparisons between academic training, perceived needs in academic training, and clinical usage may inform future training and clinical competency. We provide suggestions for developing future training, as well as for furthering clinical implementation and research. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Core competencies in clinical neuropsychology training across the world.

PubMed

Hessen, Erik; Hokkanen, Laura; Ponsford, Jennie; van Zandvoort, Martine; Watts, Ann; Evans, Jonathan; Haaland, Kathleen Y

2018-05-01

This work aimed to review main competency requirements from training models in countries with well-established specialties in clinical neuropsychology and to extract core competencies that likely will apply to clinical neuropsychologists regardless of regional and cultural context. We reviewed standards for post-graduate training in clinical neuropsychology from countries in Europe, Australia, and North America based on existing literature, presentations at international conferences, and from description of the training models from national psychological or neuropsychological associations. Despite differences, the reviewed models share similar core competencies considered necessary for a specialty in clinical neuropsychology: (1) In-depth knowledge of general psychology including clinical psychology (post-graduate level), ethical, and legal standards. (2) Expert knowledge about clinically relevant brain-behavioral relationships. (3) Comprehensive knowledge about, and skills in, related clinical disciplines. (4) In-depth knowledge about and skills in neuropsychological assessment, including decision-making and diagnostic competency according to current classification of diseases. (5) Competencies in the area of diversity and culture in relation to clinical neuropsychology. (6) Communication competency of neuropsychological findings and test results to relevant and diverse audiences. (7) Knowledge about and skills in psychological and neuropsychological intervention, including treatment and rehabilitation. All the models have undergone years of development in accordance with requirements of national health care systems in different parts of the world. Despite differences, the common core competency requirements across different regions of the world suggest generalizability of these competencies. We hope this summary can be useful as countries with less established neuropsychology training programs develop their models.

Clinical spectrum of hypopituitarism in India: A single center experience

PubMed Central

Gundgurthi, Abhay; Garg, M. K.; Bhardwaj, Reena; Brar, Karninder S.; Kharb, Sandeep; Pandit, Aditi

2012-01-01

Objectives: There is paucity of information regarding clinical profile of hypopituitarism from India. We report the clinical profile of hypopituitarism from a tertiary center in North India. Materials and Methods: This study was carried out in patients attending our endocrine center between January 2010 and December 2011. All new patients were studied prospectively and those registered before January 2010 retrospectively. Relevant clinical, hormonal, and imaging data were collected. Dynamic testing for pituitary functions was carried out as necessary. Hormonal deficiencies were defined as per prevailing recommendations. Results: This study included 113 subjects. The mean age was 38.6 ± 17.8 years (range, 4 – 76 years). There were 78 (69%) males and 35 females (31%). There were 22 subjects aged ≤18 years (childhood and adolescence) and 91 adults (>18 years). Visual disturbances were the most common presenting complaint (33%), though headache was the most common symptom (81%). Fifteen percent presented with pituitary apoplexy. Tumors comprised of 84% of cases. Hypogonadism (97%) was the most common abnormality seen followed by hypothyroidism (83.2%), hypoadrenalism (79.6%), growth hormone deficiency (88.1% of the 42 patients tested), and diabetes insipidus (13.3%). Panhypopituitarism was seen in 104 (92%) patients. There were no cases of hypopituitarism secondary to traumatic brain injury, subarachnoid hemorrhage, central nervous system infections, or cranial irradiation to extrasellar tumors. Conclusion: The most common cause of hypopituitarism at tertiary care center is pituitary tumors and the commonest presenting complaint is visual symptoms. Panhypopituitarism is present in 92% cases. PMID:23087868

[Novelties in diagnostics and treatment of prostate cancer].

PubMed

Riesz, Péter; Nyírádi, Péter

2016-03-13

Similarly to earlier years, a vast majority of novel findings were published on prostate cancer, which is the most common urological cancer. Clinical trials with long-term follow-up and promising observational studies were published. In this paper the author reviews the relevant novelties including the diagnostic use of magnetic resonance imaging and positron emission tomography/computed tomography as well as active surveillance, cytoreductive prostatectomy and medical treatment.

Characteristics of the sequence effect in Parkinson's disease.

PubMed

Kang, Suk Yun; Wasaka, Toshiaki; Shamim, Ejaz A; Auh, Sungyoung; Ueki, Yoshino; Lopez, Grisel J; Kida, Tetsuo; Jin, Seung-Hyun; Dang, Nguyet; Hallett, Mark

2010-10-15

The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer-based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo-controlled, four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.

Prevention of infectious complications after elective colorectal surgery in children: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee comprehensive review.

PubMed

Rangel, Shawn J; Islam, Saleem; St Peter, Shawn D; Goldin, Adam B; Abdullah, Fizan; Downard, Cynthia D; Saito, Jacqueline M; Blakely, Martin L; Puligandla, Pramod S; Dasgupta, Roshni; Austin, Mary; Chen, Li Ern; Renaud, Elizabeth; Arca, Marjorie J; Calkins, Casey M

2015-01-01

This goal of this review was to examine the clinical evidence in support of commonly utilized measures intended to reduce complications following elective colorectal surgery. Literature searches were performed to identify relevant studies from Medline, PubMed, and Cochrane databases. The American Pediatric Surgery Association Outcomes and Clinical Trials Committee selected eight questions to address this topic systematically in the context of three management areas: 1) appropriate utilization of systemic antibiotics for colorectal procedures, 2) reduction of stool burden through mechanical bowel preparation, and 3) intraluminal gut decontamination through use of enteral nonabsorbable antibiotics. Primary outcomes of interest included the occurrence of infectious and mechanical complications related to stool burden and intraluminal bacterial concentration (incisional surgical site infection, anastomotic leakage, and intraabdominal abscess). The evidence in support of each management category was systematically reviewed, graded, and summarized in the context of the review's primary outcomes. Practice recommendations were made as deemed appropriate by the committee. Clinical evidence in support of interventions to reduce infectious complications following colorectal surgery is derived almost exclusively from the adult literature. High-quality evidence to guide clinical practice in children is sorely needed, as the available data may have only limited relevance to pediatric colorectal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Occurrence of erythema migrans in children with Lyme neuroborreliosis and the association with clinical characteristics and outcome - a prospective cohort study.

PubMed

Backman, Kesia; Skogman, Barbro H

2018-06-11

Erythema migrans (EM) is the most common manifestation of Lyme borreliosis (LB), caused by the spirochete Borrelia burgdorferi sensu lato. The infection can disseminate into the nervous system and cause Lyme neuroborreliosis (LNB), the second most frequent LB manifestation in children. The aim of this prospective cohort study is to describe the occurrence of EM among children with LNB and to evaluate possible differences in clinical characteristics or outcome between LNB patients with and without EM. Children being evaluated for LNB in southeast Sweden during the period 2010-2014 underwent a clinical examination, laboratory testing and filled out a questionnaire regarding duration and nature of symptoms, EM and the child's health. Children were classified according to European guidelines for LNB. Clinical recovery was evaluated at a 2-month follow-up. The occurrence of EM among children with LNB was 37 out of 103 (36%). Gender, age, observed tick bite, clinical features, duration of neurological symptoms or clinical outcome did not differ significantly between LNB patients with or without EM. However, facial nerve palsy was significantly more common among children with EM in the head and neck area. EM occurred in 36% of children with LNB and the location on the head and neck was more common among children with facial nerve palsy. EM was not associated with other specific clinical characteristics or outcome. Thus, the occurrence of EM in children with LNB cannot be useful as a prognostic factor for clinical outcome. This aspect has not previously been highlighted but seems to be relevant for the paediatrician in a clinical setting.

The 50 Most Cited Articles in Invasive Neuromodulation.

PubMed

Ward, Max; Doran, Joseph; Paskhover, Boris; Mammis, Antonios

2018-06-01

Bibliometric analysis is a commonly used analytic tool for objective determination of the most influential and peer-recognized articles within a given field. This study is the first bibliometric analysis of the literature in the field of invasive neuromodulation, excluding deep brain stimulation. The objectives of this study are to identify the 50 most cited articles in invasive neuromodulation, provide an overview of the literature to assist in clinical education, and evaluate the effect of impact factor on manuscript recognition. Bibliometric analysis was performed using the Science Citation Index from the Institute for Scientific Information, accessed through the Web of Science. Search terms relevant to the field of invasive neuromodulation were used to identify the 50 most cited journal articles between 1900 and 2016. The median number of citations was 236 (range, 173-578). The most common topics among the articles were vagus nerve stimulation (n = 24), spinal cord stimulation (n = 9), and motor cortex stimulation (n = 6). Median journal impact factor was 5.57. Most of these articles (n = 19) contained level I, II, or III evidence. This analysis provides a brief look into the most cited articles within the field, many of which evaluated innovated procedures and therapies that helped to drive surgical neuromodulation forward. These landmark articles contain vital clinical and educational information that remains relevant to clinicians and students within the field and provide insight into areas of expanding research. Journal impact factor may play a significant role in determining the literary relevance and general awareness of invasive neuromodulation studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Twenty-Year Systematic Review of the Hip Pathology, Risk Factors, Treatment, and Clinical Outcomes in Artistic Athletes-Dancers, Figure Skaters, and Gymnasts.

PubMed

Bolia, Ioanna; Utsunomiya, Hajime; Locks, Renato; Briggs, Karen; Philippon, Marc J

2018-01-01

To identify (1) the predominant level of evidence of the clinical studies regarding the hip pathology, risk factors, treatment, and clinical outcomes in artistic athletes (dancers, figure skaters, and gymnasts) (2) the most commonly reported hip pathology, risk factors, treatments, and clinical outcomes in dancers, figure skaters, and gymnasts. To conduct this systematic review PubMed, EMBASE, and Scopus databases were searched for relevant studies and pertinent data were collected from the eligible articles. Included were studies which reported hip injuries in artistic athletes, the risk factors, treatment, and/or the clinical outcomes. We excluded case reports or irrelevant studies. No meta-analysis was performed because of study heterogeneity. The methodical index for nonrandomized studies (MINORS) criteria were used for quality control. Thirty-eight studies were included in the analysis. The mean MINORS score was 13.6 ± 4.6 points indicating fair quality of evidence of the included articles. The predominant level of evidence was level IV. Chondrolabral pathology and muscle injuries were the most commonly reported pathologies. We found only 2 risk factor analysis studies; however, many studies reported risk correlation between artistic sports or imaging findings and hip pathology. Treatment strategies were reported in only 7 studies, clinical outcomes are significantly underreported. Chondrolabral pathology was the most commonly reported hip pathology in artistic athletes, however, prospective cohort studies are necessary to really understand these injuries and their associated risk factors. The lack of clinical outcomes is significant and future data collection is required to assess the effectiveness of the various treatments.

Relative effectiveness assessments of oncology medicines for pricing and reimbursement decisions in European countries.

PubMed

Kleijnen, S; Lipska, I; Leonardo Alves, T; Meijboom, K; Elsada, A; Vervölgyi, V; d'Andon, A; Timoney, A; Leufkens, H G; De Boer, A; Goettsch, W G

2016-09-01

There is a debate on the added clinical value of new, expensive, anticancer treatments. Among European decision makers, the relevance of commonly used end points in trials, especially overall survival (OS), progression-free survival (PFS) and quality of life (QoL), varies, leading to the available evidence being valued differently. This research studies the extent to which the value of end points for cancer medicines differs among European decision makers. We compared guidelines and relative effectiveness assessments (REAs) of medicines for pricing or reimbursement decisions in England, France, Germany, The Netherlands, Poland, and Scotland. Anticancer medicines that received marketing authorization in Europe between 2011 and 2013 with at least four available national REAs were evaluated. A total of 79 REAs were included. Health technology assessment (HTA) guidelines indicate a preference for clinically and patient relevant end points such as OS and QoL above surrogate end points. Most guidelines do not specify whether PFS is considered a surrogate or patient-relevant end point. The number of REAs included per jurisdiction varied between 7 (The Netherlands) and 18 (Germany). OS data were included in all REAs and were the preferred end point by HTA agencies, but these data were not always mature or robust. QoL data are included in only 54% of the REAs, with a limited impact on the recommendations. PFS data are included in 70% of the REAs, but the extent to which HTA agencies find PFS relevant varies. European decision-making on relative effectiveness of anticancer medicines is affected by a gap in requested versus available clinical evidence, mainly because the regulator is willing to accept some degree of clinical uncertainty. A multi-stakeholder debate would be essential to align concrete robust evidence requirements in oncology and a collectively shared definition for relevant clinical benefit, which will benefit patients and society in general. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities.

PubMed

Schulz, Alexander; Grafe, Peter; Hagel, Christian; Bäumer, Philipp; Morrison, Helen; Mautner, Victor-Felix; Farschtschi, Said

2018-01-01

The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum. However, the clinical relevance and respective underlying pathogenesis, varies greatly among the different NF types. In this review, we summarize and interpret the latest basic research findings, as well as clinical observations, in respect of Neurofibromatosis-associated neuropathies. Copyright © 2017 Elsevier Inc. All rights reserved.

The spine in Paget’s disease

PubMed Central

Dell’Atti, C.; Lalam, R. K.; Tins, B. J.; Tyrrell, P. N. M.

2007-01-01

Paget’s disease (PD) is a chronic metabolically active bone disease, characterized by a disturbance in bone modelling and remodelling due to an increase in osteoblastic and osteoclastic activity. The vertebra is the second most commonly affected site. This article reviews the various spinal pathomechanisms and osseous dynamics involved in producing the varied imaging appearances and their clinical relevance. Advanced imaging of osseous, articular and bone marrow manifestations of PD in all the vertebral components are presented. Pagetic changes often result in clinical symptoms including back pain, spinal stenosis and neural dysfunction. Various pathological complications due to PD involvement result in these clinical symptoms. Recognition of the imaging manifestations of spinal PD and the potential complications that cause the clinical symptoms enables accurate assessment of patients prior to appropriate management. PMID:17410356

A Clinical Decision Support System for Breast Cancer Patients

NASA Astrophysics Data System (ADS)

Fernandes, Ana S.; Alves, Pedro; Jarman, Ian H.; Etchells, Terence A.; Fonseca, José M.; Lisboa, Paulo J. G.

This paper proposes a Web clinical decision support system for clinical oncologists and for breast cancer patients making prognostic assessments, using the particular characteristics of the individual patient. This system comprises three different prognostic modelling methodologies: the clinically widely used Nottingham prognostic index (NPI); the Cox regression modelling and a partial logistic artificial neural network with automatic relevance determination (PLANN-ARD). All three models yield a different prognostic index that can be analysed together in order to obtain a more accurate prognostic assessment of the patient. Missing data is incorporated in the mentioned models, a common issue in medical data that was overcome using multiple imputation techniques. Risk group assignments are also provided through a methodology based on regression trees, where Boolean rules can be obtained expressed with patient characteristics.

Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers.

PubMed

Dunnenberger, Henry M; Crews, Kristine R; Hoffman, James M; Caudle, Kelly E; Broeckel, Ulrich; Howard, Scott C; Hunkler, Robert J; Klein, Teri E; Evans, William E; Relling, Mary V

2015-01-01

Although the field of pharmacogenetics has existed for decades, practioners have been slow to implement pharmacogenetic testing in clinical care. Numerous publications describe the barriers to clinical implementation of pharmacogenetics. Recently, several freely available resources have been developed to help address these barriers. In this review, we discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of patients. Array-based preemptive testing includes a large number of relevant pharmacogenes that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to be available prior to any prescribing decision so that genomic variation may be considered as an inherent patient characteristic in the planning of therapy. This review describes the common elements among programs that have implemented preemptive genotyping and highlights key processes for implementation, including clinical decision support.

Argumentation and evidence.

PubMed

Upshur, R E G; Colak, Errol

2003-01-01

This essay explores the role of informal logic and its application in the context of current debates regarding evidence-based medicine. This aim is achieved through a discussion of the goals and objectives of evidence-based medicine and a review of the criticisms raised against evidence-based medicine. The contributions to informal logic by Stephen Toulmin and Douglas Walton are explicated and their relevance for evidence-based medicine is discussed in relation to a common clinical scenario: hypertension management. This essay concludes with a discussion on the relationship between clinical reasoning, rationality, and evidence. It is argued that informal logic has the virtue of bringing explicitness to the role of evidence in clinical reasoning, and brings sensitivity to understanding the role of dialogical context in the need for evidence in clinical decision making.

Classic hallucinogens in the treatment of addictions.

PubMed

Bogenschutz, Michael P; Johnson, Matthew W

2016-01-04

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes

PubMed Central

Naville, Magali; Bressan, Cédric; Hühns, Maja; Gock, Michael; Kühn, Florian; Volff, Jean-Nicolas; Trillet-Lenoir, Véronique

2015-01-01

Background Expression of the human endogenous retrovirus (HERV)-H family has been associated with colorectal carcinomas (CRC), yet no individual HERV-H locus expression has been thoroughly correlated with clinical data. Here, we characterized HERV-H reactivations in clinical CRC samples by integrating expression profiles, molecular patterns and clinical data. Expression of relevant HERV-H sequences was analyzed by qRT-PCR on two well-defined clinical cohorts (n = 139 pairs of tumor and adjacent normal colon tissue) including samples from adenomas (n = 21) and liver metastases (n = 16). Correlations with clinical and molecular data were assessed. Results CRC specific HERV-H sequences were validated and found expressed throughout CRC disease progression. Correlations between HERV-H expression and lymph node invasion of tumor cells (p = 0.0006) as well as microsatellite instable tumors (p < 0.0001) were established. No association with regard to age, tumor localization, grading or common mutations became apparent. Interestingly, CRC expressed elements belonged to specific young HERV-H subfamilies and their 5′ LTR often presented active histone marks. Conclusion These results suggest a functional role of HERV-H sequences in colorectal carcinogenesis. The pronounced connection with microsatellite instability warrants a more detailed investigation. Thus, HERV-H sequences in addition to tumor specific mutations may represent clinically relevant, truly CRC specific markers for diagnostic, prognostic and therapeutic purposes. PMID:26517682

Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes.

PubMed

Pérot, Philippe; Mullins, Christina Susanne; Naville, Magali; Bressan, Cédric; Hühns, Maja; Gock, Michael; Kühn, Florian; Volff, Jean-Nicolas; Trillet-Lenoir, Véronique; Linnebacher, Michael; Mallet, François

2015-11-24

Expression of the human endogenous retrovirus (HERV)-H family has been associated with colorectal carcinomas (CRC), yet no individual HERV-H locus expression has been thoroughly correlated with clinical data.Here, we characterized HERV-H reactivations in clinical CRC samples by integrating expression profiles, molecular patterns and clinical data. Expression of relevant HERV-H sequences was analyzed by qRT-PCR on two well-defined clinical cohorts (n = 139 pairs of tumor and adjacent normal colon tissue) including samples from adenomas (n = 21) and liver metastases (n = 16). Correlations with clinical and molecular data were assessed. CRC specific HERV-H sequences were validated and found expressed throughout CRC disease progression. Correlations between HERV-H expression and lymph node invasion of tumor cells (p = 0.0006) as well as microsatellite instable tumors (p < 0.0001) were established. No association with regard to age, tumor localization, grading or common mutations became apparent. Interestingly, CRC expressed elements belonged to specific young HERV-H subfamilies and their 5' LTR often presented active histone marks. These results suggest a functional role of HERV-H sequences in colorectal carcinogenesis. The pronounced connection with microsatellite instability warrants a more detailed investigation. Thus, HERV-H sequences in addition to tumor specific mutations may represent clinically relevant, truly CRC specific markers for diagnostic, prognostic and therapeutic purposes.

Infections in the differential diagnosis of Bell's palsy: a plea for performing CSF analysis.

PubMed

Henkel, Katrin; Lange, Peter; Eiffert, Helmut; Nau, Roland; Spreer, Annette

2017-04-01

Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP.

Clinically relevant variations of the superior thyroid cornu.

PubMed

Shiozawa, Thomas; Epe, P; Herlan, S; Müller, M; Tropitzsch, A; Tsiflikas, I; Hirt, B

2017-03-01

The superior thyroid cornu (STC) of the thyroid cartilage is a variable structure that maybe associated with different clinical symptoms. This study evaluates the three-dimensional anatomy of the STC. Measurements were conducted on 97 CT scans (45 male and 52 female). The protocol models a vector from the base to the tip of the STC and references the cornu to the midline. From these data, the length (C), the rotation angle (γ), the inclination angle (β), and the deviation of STC base (X 2 ) and tip (X 3 ) from the midline were measured. An additional measure of the medial inclination quotient (Q = X 3 /X 2 ) was calculated. The STC has a mean length of 13.9 ± 3.26 mm. The male STC is more bent inwards (rotation angle (γ) 60.95° vs. 12.15°; p < 0.001), and the female STC is more steep (inclination angle (β) 75.44° vs. 73.44°; p < 0.001). The mean Q in men was significantly lower (0.85 ± 0.15 vs. 0.97 ± 0.15; p < 0.001). An extreme medial deformation was found in 13.4 % of the patients. This variation is associated with Q ≤ 0.7, most of the time unilateral and more common in men (86.7 vs. 13.3 %). Furthermore, we can describe STC variations with close proximity to the common carotid artery or the cervical spine. The clinically most relevant variation of the STC seems to be the extreme medial deviation, which may lead to symptoms described with the superior thyroid cornu syndrome. The evaluation of Q in axial CT scans is easily done and may propose a helpful tool for clinical diagnostics.

A review of depression research in malaysia.

PubMed

Ng, C G

2014-08-01

Depression is a debilitating illness and has become a leading cause of morbidity globally. We aim to summarise the evidence available in regard to the prevalence, type of assessment tools used and treatment options for depression in Malaysia. Two hundred and forty seven articles related to depression were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Fifty seven articles were selected and reviewed on the basis of clinical relevance and future research implications. Findings were summarised, categorised and presented according to prevalence of depression, depression in women, depression in clinical condition, assessment tools, and treatment of depression. The prevalence of depression in Malaysia was estimated to be between 8 and 12%. The figures were higher among women of low socio-economic background or those with comorbid medical condition. The common assessment tools used in Malaysia include Beck Depression Inventory (BDI), Depression, Anxiety and Stress Scale (DASS), Patient Health Questionnaire 9 (PHQ-9) and Hospital Anxiety and Depression Scale (HADS). They were translated into the Malay language and their psychometric properties were established. Both pharmacological treatment and psychotherapy were commonly used in Malaysia, and were highly recommended in local clinical practice guidelines. There are discrepancies in the reported rates of depression in Malaysia and this needs to be addressed. There were lack of studies looking into the depression among subgroups in Malaysia especially in the male population. There were several instruments available for assessment of depression in Malaysia but their suitability for the local setting need further research. Both pharmacotherapy and psychotherapy were recommended in the local treatment guideline in Malaysia. With the emergence of generic medication, we need to compare their clinical efficacy and tolerability with original products.

Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly.

PubMed

Aarts, Nikkie; Noordam, Raymond; Hofman, Albert; Tiemeier, Henning; Stricker, Bruno H; Visser, Loes E

2016-10-01

Background Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed 'off-label' for indications not investigated in clinical trials. Objective We aimed to study indications for antidepressant use based on self-report. Also, we studied the presence of depressive symptoms associated with the self-reported indications. Setting Our study population of antidepressant users was selected based on interview data between 1997 and 2013 from the prospective population-based Rotterdam Study cohort (age >45 years). Method Antidepressant use, self-reported indication for use, and presence of depressive symptoms (Center for Epidemiological Studies Depression Scale) were based on interview. Self-reported indications were categorized by the researchers into officially approved, clinically-accepted and commonly mentioned off-label indications. Main outcome measures A score of 16 and higher on the Center for Epidemiological Studies Depression Scale was considered as indicator for clinically-relevant depressive symptoms. Results The majority of 914 antidepressant users reported 'depression' (52.4 %) as indication for treatment. Furthermore, anxiety, stress and sleep disorders were reported in selective serotonin reuptake inhibitor and other antidepressant users (ranging from 5.9 to 13.3 %). The indication 'pain' was commonly mentioned by tricyclic antidepressant users (19.0 %). Indications were statistically significantly associated with higher depressive symptom scores when compared to non-users (n = 10,979). Conclusions Depression was the main indication for antidepressant treatment. However, our findings suggest that antidepressants are also used for off-label indications, subthreshold disorders and complex situations, which were all associated with clinically-relevant depressive symptoms in the middle-aged and elderly population.

Limb length inequality: clinical implications for assessment and intervention.

PubMed

Brady, Rebecca J; Dean, John B; Skinner, T Marc; Gross, Michael T

2003-05-01

The purpose of this paper is to review relevant literature concerning limb length inequalities in adults and to make recommendations for assessment and intervention based on the literature and our own clinical experience. Literature searches were conducted in the MEDLINE, PubMed, and CINAHL databases. Limb length inequality and common classification criteria are defined and etiological factors are presented. Common methods of detecting limb length inequality include direct (tape measure methods), indirect (pelvic leveling), and radiological techniques. Interventions include shoe inserts or external shoe lift therapy for mild cases. Surgery may be appropriate in severe cases. Little agreement exists regarding the prevalence of limb length inequality, the degree of limb length inequality that is considered clinically significant, and the reliability and validity of assessment methods. Based on correlational studies, the relationship between limb length inequality and orthopaedic pathologies is questionable. Stronger support for the link between low back pain (LBP) and limb length inequality is provided by intervention studies. Methods involving palpation of pelvic landmarks with block correction have the most support for clinical assessment of limb length inequality. Standing radiographs are suggested when clinical assessment methods are unsatisfactory. Clinicians should exercise caution when undertaking intervention strategies for limb length inequality of less than 5 mm when limb length inequality has been identified with clinical techniques. Recommendations are provided regarding intervention strategies.

Can clinical governance deliver quality improvement in Australian general practice and primary care? A systematic review of the evidence.

PubMed

Phillips, Christine B; Pearce, Christopher M; Hall, Sally; Travaglia, Joanne; de Lusignan, Simon; Love, Tom; Kljakovic, Marjan

2010-11-15

To review the literature on different models of clinical governance and to explore their relevance to Australian primary health care, and their potential contributions on quality and safety. 25 electronic databases, scanning reference lists of articles and consultation with experts in the field. We searched publications in English after 1999, but a search of the German language literature for a specific model type was also undertaken. The grey literature was explored through a hand search of the medical trade press and websites of relevant national and international clearing houses and professional or industry bodies. 11 software packages commonly used in Australian general practice were reviewed for any potential contribution to clinical governance. 19 high-quality studies that assessed outcomes were included. All abstracts were screened by one researcher, and 10% were screened by a second researcher to crosscheck screening quality. Studies were reviewed and coded by four reviewers, with all studies being rated using standard critical appraisal tools such as the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two researchers reviewed the Australian general practice software. Interviews were conducted with 16 informants representing service, regional primary health care, national and international perspectives. Most evidence supports governance models which use targeted, peer-led feedback on the clinician's own practice. Strategies most used in clinical governance models were audit, performance against indicators, and peer-led reflection on evidence or performance. The evidence base for clinical governance is fragmented, and focuses mainly on process rather than outcomes. Few publications address models that enhance safety, efficiency, sustainability and the economics of primary health care. Locally relevant clinical indicators, the use of computerised medical record systems, regional primary health care organisations that have the capacity to support the uptake of clinical governance at the practice level, and learning from the Aboriginal community-controlled sector will help integrate clinical governance into primary care.

Mathematical Models of Breast and Ovarian Cancers

PubMed Central

Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

2016-01-01

Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, since answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible, in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. PMID:27259061

Consumer sleep monitors: is there a baby in the bathwater?

PubMed Central

Russo, Kathryn; Goparaju, Balaji; Bianchi, Matt T

2015-01-01

The rapid expansion of consumer sleep devices is outpacing the validation data necessary to assess the potential use of these devices in clinical and research settings. Common sleep monitoring devices utilize a variety of sensors to track movement as well as cardiac and respiratory physiology. The variety of sensors and user-specific factors offer the potential, at least theoretically, for clinically relevant information. We describe the current challenges for interpretation of consumer sleep monitoring data, since the devices are mainly used in non-medical contexts (consumer use) although medically-definable sleep disorders may commonly occur in this setting. A framework for addressing questions of how certain devices might be useful is offered. We suggest that multistage validation efforts are crucially needed, from the level of sensor data and algorithm output, to extrapolations beyond healthy adults and into other populations and real-world environments. PMID:26604847

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

Health Literacy and Atrial Fibrillation: Relevance and Future Directions for Patient-centred Care.

PubMed

Aronis, Konstantinos N; Edgar, Brittany; Lin, Wendy; Martins, Maria Auxiliadora Parreiras; Paasche-Orlow, Michael K; Magnani, Jared W

2017-01-01

Atrial fibrillation (AF) is a common cardiac arrhythmia with significant clinical outcomes, and is associated with high medical and social costs. AF is complicated for patients because of its specialised terminology, long-term adherence, symptom monitoring, referral to specialty care, array of potential interventions and potential for adversity. Health literacy is a frequently under-recognised, yet fundamental, component towards successful care in AF. Health literacy is defined as the capacity to obtain, process and understand health information, and has had markedly limited study in AF. However, health literacy could contribute to how patients interpret symptoms, navigate care, and participate in treatment evaluation and decision-making. This review aims to summarise the clinical importance and essential relevance of health literacy in AF. We focus here on central aspects of AF care that are most related to self-care, including understanding the symptoms of AF, shared decision-making, adherence and anticoagulation for stroke prevention. We discuss opportunities to enhance AF care based on findings from the literature on health literacy, and identify important gaps. Our overall objective is to articulate the importance and relevance of integrating health literacy in the care of individuals with AF.

Integration of complementary and alternative medicine information and advice in chronic disease management guidelines.

PubMed

Team, Victoria; Canaway, Rachel; Manderson, Lenore

2011-01-01

The growing evidence on the benefits and risks of complementary and alternative medicine (CAM) and its high rate of use (69% of Australians) - particularly for chronic or recurrent conditions - means increasing attention on CAM. However, few people disclose CAM use to their GP, and health professionals tend to inadequately discuss CAM-related issues with their patients, partly due to insufficient knowledge. As clinical and non-clinical chronic condition management guidelines are a means to educate primary health care practitioners, we undertook a content analysis of guidelines relevant to two common chronic conditions - cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) - to assess their provision of CAM-related information. Ten current Australian guidelines were reviewed, revealing scant CAM content. When available, the CAM-relevant information was brief, in some cases unclear, inconclusive and lacking in direction to the GP or health care provider. Although we focus on CVD and T2DM, we argue the value of all chronic condition management guidelines integrating relevant evidence-informed information and advice on CAM risks, benefits and referrals, to increase GP awareness and knowledge of appropriate CAM therapies, and potentially to facilitate doctor-client discussion about CAM.

Do systematic reviews address community healthcare professionals' wound care uncertainties? Results from evidence mapping in wound care.

PubMed

Christie, Janice; Gray, Trish A; Dumville, Jo C; Cullum, Nicky A

2018-01-01

Complex wounds such as leg and foot ulcers are common, resource intensive and have negative impacts on patients' wellbeing. Evidence-based decision-making, substantiated by high quality evidence such as from systematic reviews, is widely advocated for improving patient care and healthcare efficiency. Consequently, we set out to classify and map the extent to which up-to-date systematic reviews containing robust evidence exist for wound care uncertainties prioritised by community-based healthcare professionals. We asked healthcare professionals to prioritise uncertainties based on complex wound care decisions, and then classified 28 uncertainties according to the type and level of decision. For each uncertainty, we searched for relevant systematic reviews. Two independent reviewers screened abstracts and full texts of reviews against the following criteria: meeting an a priori definition of a systematic review, sufficiently addressing the uncertainty, published during or after 2012, and identifying high quality research evidence. The most common uncertainty type was 'interventions' 24/28 (85%); the majority concerned wound level decisions 15/28 (53%) however, service delivery level decisions (10/28) were given highest priority. Overall, we found 162 potentially relevant reviews of which 57 (35%) were not systematic reviews. Of 106 systematic reviews, only 28 were relevant to an uncertainty and 18 of these were published within the preceding five years; none identified high quality research evidence. Despite the growing volume of published primary research, healthcare professionals delivering wound care have important clinical uncertainties which are not addressed by up-to-date systematic reviews containing high certainty evidence. These are high priority topics requiring new research and systematic reviews which are regularly updated. To reduce clinical and research waste, we recommend systematic reviewers and researchers make greater efforts to ensure that research addresses important clinical uncertainties and is of sufficient rigour to inform practice.

Women with HIV are more commonly infected with non-16 and -18 high-risk HPV types.

PubMed

McKenzie, Nathalie Dauphin; Kobetz, Erin N; Hnatyszyn, James; Twiggs, Leo B; Lucci, Joseph A

2010-03-01

To review and summarize evidence from clinical, translational and epidemiologic studies which have examined the clinically relevant aspects of HPV type prevalence and cervical dysplasia in HIV-infected women. Relevant studies were identified through a MEDLINE search. References of identified reports were also used to identify additional published articles for review. HIV-infected women in different geographic regions (such as Zambia, Brazil, Rochester NY) appear to be infected with less prevalent types of HR-HPV as compared to the general population who, across all continents, are more commonly infected with types 16 and 18. Secondly, integration of HPV DNA into the host genome is no longer thought to be a necessary cause of malignant transformation of cervical cells. However, rate of integration appears to differ by the type of HPV. In fact, the types of HPV which appear to be more common in cervical dysplasia of HIV-infected women are the same types which are more likely to require integration for malignant transformation. Finally, HPV types found in HIV-infected women are relatively common and likely to persist. The most common among these types belong to the alpha-9 and -7 species which are the most carcinogenic species. Given that current vaccines target HR-HPV-16/18, the findings from the above mentioned studies may have important implications for the design of HPV vaccines that target the types of HPV associated with disease risk in HIV-infected women. HPV typing and assessment of the physical state (whether it is integrated or episomal) appear to be two valuable parameters for the prognostic evaluation of dysplastic lesions of the uterine cervix. This, however, has not yet been assessed in HIV-infected women. Recent data about the immune response in HPV/HIV co-infection may lead to understanding potential mechanisms for less virulent HPV causing malignant transformation in HIV-infected women.

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Characterization and susceptibility patterns of clinically important Enterococcus species in eastern Nepal.

PubMed

Acharya, A; Khanal, A; Kanungo, R; Mohapatra, T

2007-12-01

Life threatening infections caused by enterococcus species with multidrug resistance has emerged as a threat to medical care in the present era. This study was conducted to characterize enterococcus species isolated from different clinical samples and to detect the pattern of susceptibility to some of the commonly used antibiotics in B.P Koirala Institute of Health Sciences (BPKIHS), a tertiary care hospital in eastern Nepal. Clinical samples submitted to the microbiology unit of Central Laboratory Service (CLS) for culture and sensitivity during March 2002 - February 2003 was analyzed. Enterococcus species were identified by colony characteristics, gram staining and relevant biochemical tests. Antibiotic susceptibility test was done by the Kirby Bauer disc diffusion technique. Of 50 Enterococcus species isolated, E. faecalis was the predominant isolate (48.0%) followed by E. faecium (32.0%) and E. avium (20.0%). Eighty-eight percent of E. faecalis showed sensitivity to cephotaxime and 87.0% to vancomycin. Multiple drug resistance was observed most commonly in E. faecium. Seventeen percent of E. faecium were resistant to vancomycin and 63.0% to ciprofloxacin and 44.0% to ampicillin. On the contrary E. avium rarely showed resistance to the antimicrobials tested including vancomycin. Enterococcal infections are common nowadays specially in hospitalized patients. Inappropriate use of antibiotics in clinical practice and poultry should be discouraged to prevent the emergence of multidrug resistant species.

New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

PubMed

Ollague Sierra, Jose E; Ollague Torres, Jose M

2013-04-01

Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

The wisdom of the commons: ensemble tree classifiers for prostate cancer prognosis

PubMed Central

Koziol, James A.; Feng, Anne C.; Jia, Zhenyu; Wang, Yipeng; Goodison, Seven; McClelland, Michael; Mercola, Dan

2009-01-01

Motivation: Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. Results: Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors. Contact: dmercola@uci.edu PMID:18628288

One Small Step for the Gram Stain, One Giant Leap for Clinical Microbiology.

PubMed

Thomson, Richard B

2016-06-01

The Gram stain is one of the most commonly performed tests in the clinical microbiology laboratory, yet it is poorly controlled and lacks standardization. It was once the best rapid test in microbiology, but it is no longer trusted by many clinicians. The publication by Samuel et al. (J. Clin. Microbiol. 54:1442-1447, 2016, http://dx.doi.org/10.1128/JCM.03066-15) is a start for those who want to evaluate and improve Gram stain performance. In an age of emerging rapid molecular results, is the Gram stain still relevant? How should clinical microbiologists respond to the call to reduce Gram stain error rates? Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Topical, Biological and Clinical Challenges in the Management of Patients with Acne Vulgaris

PubMed Central

Al-Hammadi, Anwar; Al-Ismaily, Abla; Al-Ali, Sameer; Ramadurai, Rajesh; Jain, Rishi; McKinley-Grant, Lynn; Mughal, Tariq I.

2016-01-01

Acne vulgaris is one of the most common chronic inflammatory skin disorders among adolescents and young adults. It is associated with substantial morbidity and, rarely, with mortality. The exact worldwide incidence and prevalence are currently unknown. Current challenges involve improving understanding of the underlying pathophysiology of acne vulgaris and developing a practical treatment consensus. Expert panel discussions were held in 2013 and 2014 among a group of scientists and clinicians from the Omani and United Arab Emirate Dermatology Societies to ascertain the current optimal management of acne vulgaris, identify clinically relevant end-points and construct suitable methodology for future clinical trial designs. This article reviews the discussions of these sessions and recent literature on this topic. PMID:27226905

[Standard operating procedures (SOPs) for palliative care : Presence and relevance of palliative SOPs within the network of German Comprehensive Cancer Centers (CCCs) funded by the German Cancer Aid].

PubMed

Stachura, P; Berendt, J; Stiel, S; Schuler, U S; Ostgathe, C

2017-02-01

Standard operating procedures (SOPs) can contribute to the improvement of patient care. Survey the presence and relevance of SOPs for palliative care (PC) within the network of German Comprehensive Cancer Centers (CCCs) funded by the German Cancer Aid. In a descriptive survey, palliative care services within 15 CCCs funded by the German Cancer Aid were asked to rate availability and thematic relevance of (1) symptom-related, (2) clinical pathways and (3) measures- and processes-oriented SOPs using a structured questionnaire. Pain management SOPs were the most common (n =11; 73 %). The most thematic relevance showed SOPs dedicated to pain management, care in the last days of life and delirium and other neuro-psychiatric diseases (each n =13; 87 %), followed by bowel obstruction, dyspnoea, nausea and palliative sedation (each n =12; 80 %). There is a wide gap between availability and perceived relevance of palliative care SOPs within the network of German CCCs funded by the German Cancer Aid. It is obvious that there is a need for further development of relevant SOPs in palliative care.

PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

PubMed

Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

2016-01-01

Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer 64 Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

From data to evidence: evaluative methods in evidence-based medicine.

PubMed

Landry, M D; Sibbald, W J

2001-11-01

The amount of published information is increasing exponentially, and recent technologic advances have created systems whereby mass distribution of this information can occur at an infinite rate. This is particularly true in the broad field of medicine, as the absolute volume of data available to the practicing clinician is creating new challenges in the management of relevant information flow. Evidence-based medicine (EBM) is an information management and learning strategy that seeks to integrate clinical expertise with the best evidence available in order to make effective clinical decisions that will ultimately improve patient care. The systematic approach underlying EBM encourages the clinician to formulate specific and relevant questions, which are answered in an iterative manner through accessing the best available published evidence. The arguments against EBM stem from the idea that there are inherent weaknesses in research methodologies and that emphasis placed on published research may ignore clinical skills and individual patient needs. Despite these arguments, EBM is gaining momentum and is consistently used as a method of learning and improving health care delivery. However, if EBM is to be effective, the clinician needs to have a critical understanding of research methodology in order to judge the value and level of a particular data source. Without critical analysis of research methodology, there is an inherent risk of drawing incorrect conclusions that may affect clinical decision-making. Currently, there is a trend toward using secondary pre-appraised data rather than primary sources as best evidence. We review the qualitative and quantitative methodology commonly used in EBM and argue that it is necessary for the clinician to preferentially use primary rather than secondary sources in making clinically relevant decisions.

Predictive value of auscultation of femoropopliteal arteries.

PubMed

Kaufmann, Carla; Jacomella, Vincenzo; Kovacicova, Ludmila; Husmann, Marc; Clemens, Robert K; Thalhammer, Christopf; Amann-Vesti, Beatrice R

2013-03-05

Femoropopliteal bruits indicate flow turbulences and increased blood flow velocity, usually caused by an atherosclerotic plaque or stenosis. No data exist on the quality of bruits as a means for quantifying the degree of stenosis. We therefore conducted a prospective observational study to investigate the sensitivity and specificity of femoropopliteal auscultation, differentiated on the basis of bruit quality, to detect and quantify clinically relevant stenoses in patients with symptomatic and asymptomatic peripheral arterial disease (PAD). Patients with known chronic and stable PAD were recruited in the outpatient clinic. We included patients with known PAD and an ankle-brachial index (ABI) <0.90 and/or an ABI ≥0.90 with a history of lower limb revascularisation. Auscultation was performed independently by three investigators with varied clinical experience after a 10-minute period of rest. Femoropopliteal lesions were classified as follows: normal vessel wall or slight wall thickening (<20%), atherosclerotic plaque with below 50% reduction of the vessel lumen, prestenotic/intrastenotic ratio over 2.5 (<70%), over 3.5 (<99%) and complete occlusion (100%). Weighted Cohen's κ coefficients for differentiated auscultation were low in all vascular regions and did not differ between investigators. Sensitivity was low in most areas with an increase after exercise. The highest sensitivity in detecting relevant (>50%) stenosis was found in the common femoral artery (86%). Vascular auscultation is known to be of great use in routine clinical practice in recognising arterial abnormalities. Diagnosis of PAD is based on various diagnostic tools (pulse palpation, ABI measurement) and auscultation can localise relevant stenosis. However, auscultation alone is of limited sensitivity and specificity in grading stenosis in femoropopliteal arteries. Where PAD is clinically suspected further diagnostic tools, especially colour-coded duplex ultrasound, should be employed to quantify the underlying lesion.

A Short Profile of Hypnotherapy Licensure in Israel.

PubMed

Binyaminy, Binyamin; Haas, Eric J

2016-01-01

In Israel, only physicians, dentists, and psychologists who complete an accredited licensing process may practice hypnosis. This study examines the characteristics of hypnotherapists compared to nonhypnotherapists in the same discipline. All hypnotherapists in Israel were compared to nonhypnotherapist health professionals. There are more subspecialists among hypnotists, and the most common specialties were psychiatry, pediatric dentistry, and clinical psychology. These findings imply self-sorting of hypnotists as a result of the regulation in Israel. Licensure of hypnotherapists could be useful in other countries by comprehensive follow-up of all licensed hypnotists and by improving public and health professional perceptions of the field and its relevance to clinical practice.

A clinical guide to needle desensitization for the paediatric patient.

PubMed

Taylor, Greig D; Campbell, Caroline

2015-05-01

Needle phobia is a common problem encountered by dental practitioners and it can pose a challenge, especially in the paediatric patient. Needle desensitization can be used for patients who have needle fear or phobia and help them overcome this by repeated, non-threatening and controlled contacts. This paper will describe an accepted technique of needle desensitization and work through the steps required to achieve a successful outcome of local anaesthesia being delivered in a calm, safe and controlled manner. Clinical Relevance: Needle desensitization is an effective technique which can be used to enable a needle phobic patient to receive a dental injection.

A systems view of health care for the poor.

PubMed Central

Prasad, N.

1989-01-01

A systems view is a synthesis of health policy, medical sociology, public health, and common clinical problems to describe the current crisis in health care for the poor. Medical sociology and public health are particularly relevant to understand the complexity of clinical issues. Although preventive medicine is in desuetude, it is crucial if we are to reduce the future liability of postponed medical care among the poor. Medicaid metamorphosed to Medicare, as half of its outlays are spent on care of the elderly in nursing homes. Health care for the poor will remain a moral challenge to the architects of health policy and the medical profession. PMID:2659807

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

PubMed

Li, Zhaoyang; Easton, Rachael

2018-01-01

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

PubMed Central

Easton, Rachael

2018-01-01

ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

An ontologically founded architecture for information systems in clinical and epidemiological research.

PubMed

Uciteli, Alexandr; Groß, Silvia; Kireyev, Sergej; Herre, Heinrich

2011-08-09

This paper presents an ontologically founded basic architecture for information systems, which are intended to capture, represent, and maintain metadata for various domains of clinical and epidemiological research. Clinical trials exhibit an important basis for clinical research, and the accurate specification of metadata and their documentation and application in clinical and epidemiological study projects represents a significant expense in the project preparation and has a relevant impact on the value and quality of these studies.An ontological foundation of an information system provides a semantic framework for the precise specification of those entities which are presented in this system. This semantic framework should be grounded, according to our approach, on a suitable top-level ontology. Such an ontological foundation leads to a deeper understanding of the entities of the domain under consideration, and provides a common unifying semantic basis, which supports the integration of data and the interoperability between different information systems.The intended information systems will be applied to the field of clinical and epidemiological research and will provide, depending on the application context, a variety of functionalities. In the present paper, we focus on a basic architecture which might be common to all such information systems. The research, set forth in this paper, is included in a broader framework of clinical research and continues the work of the IMISE on these topics.

Baccalaureate Minority Nursing Students Perceived Barriers and Facilitators to Clinical Education Practices: An Integrative Review.

PubMed

Graham, Crystal L; Phillips, Shannon M; Newman, Susan D; Atz, Teresa W

2016-01-01

This integrative review synthesized baccalaureate minority nursing students' perceptions of their clinical experiences. The diversity of the nursing workforce does not mirror the United States population. Attrition rates of minority nursing students remain higher than rates for White students. Literature examining facilitators and barriers to minority student success predominantly focuses on academic factors, excluding those relevant to clinical education. An integrative review using literature from nursing and education. Three common perceived barriers were identified: discrimination from faculty, peers, nursing staff, and patients; bias in faculty grading practices; and isolation. Although little is known about the relationship between clinical failures and overall attrition, this review provides evidence that minority students encounter significant barriers in clinical education. To increase the diversity of the nursing workforce, faculty must address these issues and make modifications to ensure an equal opportunity at a quality education for all students.

A First Step towards a Clinical Decision Support System for Post-traumatic Stress Disorders.

PubMed

Ma, Sisi; Galatzer-Levy, Isaac R; Wang, Xuya; Fenyö, David; Shalev, Arieh Y

2016-01-01

PTSD is distressful and debilitating, following a non-remitting course in about 10% to 20% of trauma survivors. Numerous risk indicators of PTSD have been identified, but individual level prediction remains elusive. As an effort to bridge the gap between scientific discovery and practical application, we designed and implemented a clinical decision support pipeline to provide clinically relevant recommendation for trauma survivors. To meet the specific challenge of early prediction, this work uses data obtained within ten days of a traumatic event. The pipeline creates personalized predictive model for each individual, and computes quality metrics for each predictive model. Clinical recommendations are made based on both the prediction of the model and its quality, thus avoiding making potentially detrimental recommendations based on insufficient information or suboptimal model. The current pipeline outperforms the acute stress disorder, a commonly used clinical risk factor for PTSD development, both in terms of sensitivity and specificity.

Prediction of clinical depression scores and detection of changes in whole-brain using resting-state functional MRI data with partial least squares regression

PubMed Central

Shimizu, Yu; Yoshimoto, Junichiro; Takamura, Masahiro; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2017-01-01

In diagnostic applications of statistical machine learning methods to brain imaging data, common problems include data high-dimensionality and co-linearity, which often cause over-fitting and instability. To overcome these problems, we applied partial least squares (PLS) regression to resting-state functional magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional representation that relates symptoms to brain activity and that predicts clinical measures. Our experimental results, based upon data from clinically depressed patients and healthy controls, demonstrated that PLS and its kernel variants provided significantly better prediction of clinical measures than ordinary linear regression. Subsequent classification using predicted clinical scores distinguished depressed patients from healthy controls with 80% accuracy. Moreover, loading vectors for latent variables enabled us to identify brain regions relevant to depression, including the default mode network, the right superior frontal gyrus, and the superior motor area. PMID:28700672

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report

PubMed Central

Carpenter, Paul A.; Kitko, Carrie L.; Elad, Sharon; Flowers, Mary E.D.; Gea-Banacloche, Juan C.; Halter, Jörg P.; Hoodin, Flora; Johnston, Laura; Lawitschka, Anita; McDonald, George B.; Opipari, Anthony W.; Savani, Bipin N.; Schultz, Kirk R.; Smith, Sean R.; Syrjala, Karen L.; Treister, Nathaniel; Vogelsang, Georgia B.; Williams, Kirsten M.; Pavletic, Steven Z.; Martin, Paul J.; Lee, Stephanie J.; Couriel, Daniel R.

2016-01-01

The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence. PMID:25838185

What Is the International Classification of Functioning, Disability and Health and Why Is It Relevant to Audiology?

PubMed Central

Meyer, Carly; Grenness, Caitlin; Scarinci, Nerina; Hickson, Louise

2016-01-01

The World Health Organization's International Classification of Functioning, Disability and Health (ICF) is widely used in disability and health sectors as a framework to describe the far-reaching effects of a range of health conditions on individuals. This biopsychosocial framework can be used to describe the experience of an individual in the components of body functions, body structures, and activities and participation, and it considers the influence of contextual factors (environmental and personal) on these components. Application of the ICF in audiology allows the use of a common language between health care professionals in both clinical and research settings. Furthermore, the ICF is promoted as a means of facilitating patient-centered care. In this article, the relevance and application of the ICF to audiology is described, along with clinical examples of its application in the assessment and management of children and adults with hearing loss. Importantly, the skills necessary for clinicians to apply the ICF effectively are discussed. PMID:27489397

[Pathological and metabolic bone diseases: Clinical importance for fracture treatment].

PubMed

Oheim, R

2015-12-01

Pathological and metabolic bone diseases are common and relevant occurrences in orthopedics and trauma surgery; however, fractures are often treated as being the illness itself and not seen as the symptom of an underlying bone disease. This is why further diagnostics and systemic treatment options are often insufficiently considered in the routine treatment of fractures. This review focuses on osteoporosis, osteopetrosis, hypophosphatasia and Paget's disease of bone.In patients with osteoporotic vertebral or proximal femur fractures, pharmaceutical treatment to prevent subsequent fractures is an integral part of fracture therapy together with surgical treatment. Osteopetrosis is caused by compromised osteoclastic bone resorption; therefore, even in the face of an elevated bone mass, vitamin D3 supplementation is crucial to avoid clinically relevant hypocalcemia. Unspecific symptoms of the musculoskeletal system, especially together with stress fractures, are typically found in patients suffering from hypophosphatasia. In these patients measurement of alkaline phosphatase shows reduced enzyme activity. Elevated levels of alkaline phosphatase are found in Paget's disease of bone where bisphosphonates are still the treatment of choice.

The Role of Emotion in Psychological Therapy

PubMed Central

Ehrenreich, Jill T.; Fairholme, Christopher P.; Buzzella, Brian A.; Ellard, Kristen K.; Barlow, David H.

2008-01-01

This Special Issue of Clinical Psychology: Science and Practice provides a series of articles detailing efforts to consider the concepts of emotion and emotion regulation in relation to clinical assessment and psychopathology intervention efforts across the lifespan. In our commentary, we review some common themes and challenges presented in these articles to move forward the discussion of emotion’s role in psychological therapy. We discuss efforts to conceptualize the role of context in defining emotion concepts and maximizing the relevancy of such concepts to treatment. We review the importance of imbuing efforts to develop emotion-focused treatments with emphases on positive, as well as negative, emotions and flexibility in the expression of these emotions. We also highlight the relevance of a lifespan developmental approach to the accurate use of emotion and emotion regulation concepts within treatment. Finally, we discuss the application of these issues to our own treatment development and evaluation efforts regarding a unified approach to the treatment of emotional disorders in adults and adolescents. PMID:18843381

Prevalence and clinical relevance of Staphylococcus warneri in the neonatal intensive care unit.

PubMed

Cimiotti, Jeannie P; Haas, Janet P; Della-Latta, Phyllis; Wu, Fann; Saiman, Lisa; Larson, Elaine L

2007-03-01

To describe the prevalence of Staphylococcus warneri on the hands of nurses and the clinical relevance of this organism among neonates in the neonatal intensive care unit (NICU). Prospective cohort study that examined the microbial flora on the hands of nurses and clinical isolates recovered from neonates during a 23-month period (March 1, 2001, through January 31, 2003). Two high-risk NICUs in New York City. All neonates hospitalized in the NICUs for more than 24 hours and all full-time nurses from the same NICUs who volunteered to participate. At baseline and then every 3 months, samples for culture were obtained from each nurse's cleaned dominant hand. Pulsed-field electrophoresis compared S. warneri isolates from neonates and staff. Samples for culture (n=834) were obtained from the hands of 119 nurses; 520 (44%) of the 1,195 isolates of coagulase-negative staphylococci recovered were identified as S. warneri. Of the 647 clinically relevant isolates recovered from neonates, 17 (8%) of the 202 isolates that were identified to species level were S. warneri. Pulsed-field electrophoresis revealed a common strain of S. warneri that was shared among the nurses and neonates. Furthermore, 117 (23%) of 520 S. warneri isolates from nurses' hands had minimum inhibitory concentrations for vancomycin of 4 mu g/mL, which indicate decreasing susceptibility. Our findings that S. warneri can be pathogenic in neonates, is a predominant species of coagulase-negative staphylococci cultured from the hands of nurses, and has decreased vancomycin susceptibility underscore the importance of continued surveillance for vancomycin resistance and pathogenicity in pediatric care settings.

Prevalence of statin-drug interactions in older people: a systematic review.

PubMed

Thai, Michele; Reeve, Emily; Hilmer, Sarah N; Qi, Katie; Pearson, Sallie-Anne; Gnjidic, Danijela

2016-05-01

Statins are among the most frequently prescribed medications internationally. Older people are commonly prescribed multiple medications and are at an increased risk of drug-drug interactions, including statin-drug interactions. The aim of this study was to conduct a systematic review of current evidence on the prevalence of statin-drug interactions in older people. A systematic search of observational studies in Embase, Medline, and PubMed was conducted. Articles were included if they were published in English during the period July 2000-July 2014 and reported on the prevalence of statin-drug interactions in people over 65 years of age. Two reviewers independently assessed the articles for eligibility and extracted the data. The search returned 1556 eligible articles. A total of 19 articles met the inclusion criteria. In studies (n = 7) that focused on statin users only, the prevalence of potential statin-drug interactions assessed using different measures ranged from 0.19 to 33.0 %. In studies that examined drug interactions across a population of both statin users and non-users (n = 12), the prevalence of potential statin-drug interactions ranged from 0.1 to 7.1 % (n = 8), and the prevalence of clinically relevant statin-drug interactions ranged from 1.5 to 4 % (n = 4). Current published evidence suggests substantial variations in the prevalence of statin-drug interactions and their clinical relevance. Further studies are necessary to provide a better understanding of the prevalence of clinically significant statin-drug interactions, the medications most frequently contributing to statin-drug interactions, and impact on relevant clinical outcomes in older people.

[Design of computerised database for clinical and basic management of uveal melanoma].

PubMed

Bande Rodríguez, M F; Santiago Varela, M; Blanco Teijeiro, M J; Mera Yañez, P; Pardo Perez, M; Capeans Tome, C; Piñeiro Ces, A

2012-09-01

The uveal melanoma is the most common primary intraocular tumour in adults. The objective of this work is to show how a computerised database has been formed with specific applications, for clinical and research use, to an extensive group of patients diagnosed with uveal melanoma. For the design of the database a selection of categories, attributes and values was created based on the classifications and parameters given by various authors of articles which have had great relevance in the field of uveal melanoma in recent years. The database has over 250 patient entries with specific information on their clinical history, diagnosis, treatment and progress. It enables us to search any parameter of the entry and make quick and simple statistical studies of them. The database models have been transformed into a basic tool for clinical practice, as they are an efficient way of storing, compiling and selective searching of information. When creating a database it is very important to define a common strategy and the use of a standard language. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression of the systemic and ocular forms.

PubMed

Rubinsky-Elefant, G; Hirata, C E; Yamamoto, J H; Ferreira, M U

2010-01-01

Although human toxocariasis ranks among the most common zoonotic infections worldwide, it remains relatively unknown to the public. The causal agents are the nematode parasites Toxocara canis and T. cati, whose definitive hosts are dogs and cats, respectively. When embryonated eggs are accidentally ingested by humans, larvae hatch in the small intestine, penetrate the intestinal wall and migrate, via the bloodstream, to the liver, lungs, muscles, eye and central nervous system. Although most human infections are asymptomatic, two well-defined clinical syndromes are classically recognised: visceral larva migrans (a systemic disease caused by larval migration through major organs) and ocular larva migrans (a disease limited to the eyes and optic nerves). Two less-severe syndromes have recently been described, one mainly in children (covert toxocariasis) and the other mainly in adults (common toxocariasis). Here, the current laboratory diagnosis, epidemiology and main clinical features of both the systemic and ocular forms of human toxocariasis are reviewed. New developments in serological diagnosis are described, the available seroprevalence data are analysed, and the results of relevant clinical studies that have been published over the last decade are explored, to provide an updated overview of this neglected but highly prevalent human infection.

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

PubMed

Sillem, M; Rabe, T; Runnebaum, B

1997-01-01

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Intense imagery movements: a common and distinct paediatric subgroup of motor stereotypies.

PubMed

Robinson, Sally; Woods, Martin; Cardona, Francesco; Baglioni, Valentina; Hedderly, Tammy

2014-12-01

The aim of this article is to describe a subgroup of children who presented with stereotyped movements in the context of episodes of intense imagery. This is of relevance to current discussions regarding the clinical usefulness of diagnosing motor stereotypies during development. The sample consisted of 10 children (nine males, one female; mean age 8y 6mo [SD 2y 5mo], range 6-15y). Referrals were from acute paediatricians, neurologists, and tertiary epilepsy services. Children were assessed by multidisciplinary teams with expertise in paediatric movement disorders. Stereotypies presented as paroxysmal complex movements involving upper and lower limbs. Imagery themes typically included computer games (60%), cartoons/films (40%), and fantasy scenes (30%). Comorbid developmental difficulties were reported for 80% of children. Brain imaging and electrophysiological investigations had been conducted for 50% of the children before referral to the clinic. The descriptive term 'intense imagery movements' (IIM) was applied if (after interview) the children reported engaging in acts of imagery while performing stereotyped movements. We believe these children may form a common and discrete stereotypy subgroup, with the concept of IIM being clinically useful to ensure the accurate diagnosis and clinical management of this paediatric movement disorder. © 2014 Mac Keith Press.

Systematic review: the management of chronic diarrhoea due to bile acid malabsorption.

PubMed

Wilcox, C; Turner, J; Green, J

2014-05-01

Bile acid malabsorption (BAM) is a common, yet under-recognised, cause of chronic diarrhoea, with limited guidance available on the appropriate management of patients with BAM. To summarise the evidence supporting different treatments available for patients with bile acid malabsorption, noting their impact on clinical outcomes, tolerability and associated side effects. A literature search was conducted through PubMed, the Cochrane Database of Systematic Reviews and Scopus. Relevant articles studied patients who had been diagnosed with BAM and were clinically assessed before and after therapy. A total of 30 relevant publications (1241 adult patients) were identified, which investigated the clinical response to drugs, including colestyramine, colestipol, colesevelam, aluminium hydroxide and obeticholic acid. The most commonly used diagnostic test of bile acid malabsorption was the SeHCAT test (24 studies). Colestyramine treatment was by far the most studied of these agents, and was successful in 70% of 801 patients (range: 63-100%). Colestyramine and colestipol are generally effective treatments of gastrointestinal symptoms from BAM, but may be poorly tolerated and reduce the bioavailability of co-administered agents. Alternative therapies (including colesevelam and aluminium hydroxide) as well as dietary intervention may also have a role, and the promising results of the first proof-of-concept study of obeticholic acid suggest that its novel approach may have an exciting future in the treatment of this condition. Future trials should employ accurate diagnostic testing and be conducted over longer periods so that the long-term benefits and tolerability of these different approaches can be evaluated. © 2014 John Wiley & Sons Ltd.

Treating nausea and vomiting in palliative care: a review

PubMed Central

Glare, Paul; Miller, Jeanna; Nikolova, Tanya; Tickoo, Roma

2011-01-01

Nausea and vomiting are portrayed in the specialist palliative care literature as common and distressing symptoms affecting the majority of patients with advanced cancer and other life-limiting illnesses. However, recent surveys indicate that these symptoms may be less common and bothersome than has previously been reported. The standard palliative care approach to the assessment and treatment of nausea and vomiting is based on determining the cause and then relating this back to the “emetic pathway” before prescribing drugs such as dopamine antagonists, antihistamines, and anticholinergic agents which block neurotransmitters at different sites along the pathway. However, the evidence base for the effectiveness of this approach is meager, and may be in part because relevance of the neuropharmacology of the emetic pathway to palliative care patients is limited. Many palliative care patients are over the age of 65 years, making these agents difficult to use. Greater awareness of drug interactions and QTc prolongation are emerging concerns for all age groups. The selective serotonin receptor antagonists are the safest antiemetics, but are not used first-line in many countries because there is very little scientific rationale or clinical evidence to support their use outside the licensed indications. Cannabinoids may have an increasing role. Advances in interventional gastroenterology are increasing the options for nonpharmacological management. Despite these emerging issues, the approach to nausea and vomiting developed within palliative medicine over the past 40 years remains relevant. It advocates careful clinical evaluation of the symptom and the person suffering it, and an understanding of the clinical pharmacology of medicines that are available for palliating them. PMID:21966219

Spectrum of magnetic resonance imaging findings in clinical glenohumeral instability

PubMed Central

Jana, Manisha; Srivastava, Deep Narayan; Sharma, Raju; Gamanagatti, Shivanand; Nag, Hiralal; Mittal, Ravi; Upadhyay, Ashish Dutt

2011-01-01

The glenohumeral joint is the most commonly dislocated joint in the body, and anterior instability is the most common type of shoulder instability. Depending on the etiology and the age of the patient, there may be associated injuries, for example, to the anterior-inferior labro-ligamentous structures (in young individuals with traumatic instability) or to the bony components (commoner in the elderly), which are best visualized using MRI and MR arthrography. Anterior instability is associated with a Bankart lesion and its variants and abnormalities of the anterior band of the inferior glenohumeral ligament (IGHL), whereas posterior instability is associated with reverse Bankart and reverse Hill-Sachs lesions. Cases of multidirectional instability often have no labral pathology on imaging but show specific osseous changes including increased chondrolabral retroversion. This article reviews the relevant anatomy in brief and describes the MRI findings in each type, with the imaging features of the common abnormalities. PMID:21799591

Multiplex Real-Time PCR Detection of Intestinal Protozoa in HIV-Infected Children in Malawi, Enterocytozoon Bieneusi is Common and Associated with Gastrointestinal Complaints and May Delay BMI (Nutritional Status) Recovery.

PubMed

Huibers, Minke H W; Moons, Peter; Maseko, Nelson; Gushu, Monfort B; Iwajomo, Oluwadamilola H; Heyderman, Robert S; van Hensbroek, Michael Boele; Brienen, Eric A; van Lieshout, Lisette; Calis, Job C J

2018-05-14

Intestinal protozoa are common opportunistic infections in HIV patients. Longitudinal studies on either the clinical relevance, or the effect of immune reconstitution by anti-retroviral therapy on intestinal protozoan infections are children is lacking however. This study investigates prevalence and clinical relevance of intestinal protozoa in HIV-infected Malawian children prior to and during their first year of ART. Stool samples collected at enrolment and during follow-up were tested for non-opportunistic (Giardia lamblia, Dientamoeba fragilis, Entamoeba histolytica) and opportunistic protozoa (Entroctytoon bieneusi, Encephalitozoon spp., Cryptosporidium spp and Cystoisospora belli) using multiplex real-time Polymerase Chain Reaction (PCR). Associations between infections and clinical symptoms were evaluated using univariate methods. Non-opportunistic and opportunistic protozoa were detected in 40%(14/35) and 46%(16/35) of children at baseline respectively. E. bieneusi was the most prevalent protozoa (37%, 13/35) and associated with gastrointestinal complaints(43% in positive (10/13) versus 18% (4/22) in E. bieneusi-negative children, p=0.001). Body Mass Index (BMI) recovery during 12 months of ART was more commonly delayed in E. bieneusi-positive (+0.29+SD 0.83) than E. bieneusi-negative children (+1.03+SD 1.25; p=0.05). E. bieneusi was not detected after 12 months of ART. E. bieneusi was the most prevalent opportunistic intestinal protozoa, present in over a third of study participants prior to initiation of ART. Although all children cleared E.bieneusi after 12 months of ART, E. bieneusi was associated with gastro-intestinal complaints and may delay BMI recovery. Trials to assess effect of treatment of E. bieneusi on nutritional status should be considered in HIV-infected African children.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

On the assessment of coordination between upper extremities: towards a common language between rehabilitation engineers, clinicians and neuroscientists.

PubMed

Shirota, Camila; Jansa, Jelka; Diaz, Javier; Balasubramanian, Sivakumar; Mazzoleni, Stefano; Borghese, N Alberto; Melendez-Calderon, Alejandro

2016-09-08

Well-developed coordination of the upper extremities is critical for function in everyday life. Interlimb coordination is an intuitive, yet subjective concept that refers to spatio-temporal relationships between kinematic, kinetic and physiological variables of two or more limbs executing a motor task with a common goal. While both the clinical and neuroscience communities agree on the relevance of assessing and quantifying interlimb coordination, rehabilitation engineers struggle to translate the knowledge and needs of clinicians and neuroscientists into technological devices for the impaired. The use of ambiguous definitions in the scientific literature, and lack of common agreement on what should be measured, present large barriers to advancements in this area. Here, we present the different definitions and approaches to assess and quantify interlimb coordination in the clinic, in motor control studies, and by state-of-the-art robotic devices. We then propose a taxonomy of interlimb activities and give recommendations for future neuroscience-based robotic- and sensor-based assessments of upper limb function that are applicable to the everyday clinical practice. We believe this is the first step towards our long-term goal of unifying different fields and help the generation of more consistent and effective tools for neurorehabilitation.

Visual impairment from uveitis in a reference hospital of Southeast Brazil: a retrospective review over a twenty years period.

PubMed

Silva, Luci Meire Pereira da; Muccioli, Cristina; Oliveira, Filipe de; Arantes, Tiago Eugênio; Gonzaga, Lucas Renó; Nakanami, Célia Regina

2013-01-01

To identify the frequency and causes of uveitis leading to visual impairment in patients referred to the Low Vision Service - Department of Ophthalmology - UNIFESP, over a twenty years period. In a retrospective study, medical records of 5,461 patients were reviewed. Data from the first clinical evaluation at the Low Vision Service were collected, patient's age, gender and cause of visual impairment were analyzed. Patients with uveitis had their chart reviewed for anatomical classification and clinical diagnosis. The mean age of the patients referred to the Low Vision Service was 42.86 years and the mean age of patients with uveitis diagnosis was 25.51 years. Retinal disorders were the most common cause of visual impairment (N=2,835 patients; 51.9%) followed by uveitis (862 patients, 15.7%). Uveitis was posterior in 792 patients (91.9% of uveitis) and toxoplasmosis was the most common diagnosis (765 patients, 88.7%). In our study, uveitis represents the second cause of visual impairment in patients referred for visual rehabilitation and toxoplasmic retinochoroiditis was the most common clinical diagnosis. It affects a young working age population with a relevant social and economic impact, but the early diagnosis and treatment can improve the quality of life of these patients.

Preemptive Clinical Pharmacogenetics Implementation: Current programs in five United States medical centers

PubMed Central

Dunnenberger, Henry M.; Crews, Kristine R.; Hoffman, James M.; Caudle, Kelly E.; Broeckel, Ulrich; Howard, Scott C.; Hunkler, Robert J.; Klein, Teri E.; Evans, William E.; Relling, Mary V.

2015-01-01

Although the field of pharmacogenetics has existed for decades, the implementation of, pharmacogenetic testing in clinical care has been slow. There are numerous publications, describing the barriers to clinical implementation of pharmacogenetics. Recently, several freely, available resources have been developed to help address these barriers. In this review we, discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of, patients. Array-based preemptive testing includes a large number of relevant pharmacogenes, that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to, be available prior to any prescribing decision so that genomic variation may be considered as, an inherent patient characteristic in the planning of therapy. This review describes the common, elements among programs that have implemented preemptive genotyping and highlights key, processes for implementation, including clinical decision support. PMID:25292429

Conducting Clinical Research Using Crowdsourced Convenience Samples.

PubMed

Chandler, Jesse; Shapiro, Danielle

2016-01-01

Crowdsourcing has had a dramatic impact on the speed and scale at which scientific research can be conducted. Clinical scientists have particularly benefited from readily available research study participants and streamlined recruiting and payment systems afforded by Amazon Mechanical Turk (MTurk), a popular labor market for crowdsourcing workers. MTurk has been used in this capacity for more than five years. The popularity and novelty of the platform have spurred numerous methodological investigations, making it the most studied nonprobability sample available to researchers. This article summarizes what is known about MTurk sample composition and data quality with an emphasis on findings relevant to clinical psychological research. It then addresses methodological issues with using MTurk--many of which are common to other nonprobability samples but unfamiliar to clinical science researchers--and suggests concrete steps to avoid these issues or minimize their impact.

Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

PubMed Central

Irani, Sarosh R; Gelfand, Jeffrey M; Al-Diwani, Adam; Vincent, Angela

2014-01-01

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined. PMID:24930434

A narrative review on cervical interventions in adults with chronic whiplash-associated disorder

PubMed Central

Yeung, Euson; Tong, Tiffany; Reed, Nick

2018-01-01

Introduction Whiplash injuries are common in society, but clinical interventions are inconclusive on the most effective treatment. Research and reviews have been completed with the goal of determining clinical interventions that are effective for whiplash injuries and disorders, but literature has not recently been summarised on best practices for cervical spine interventions for adults with chronic whiplash. Purpose The objective of this narrative review is to update and expand on previous works, to provide recommendations for clinical interventions and future research in the area of cervical spine rehabilitation for adults with chronic whiplash-associated disorder. Method The Arskey and O’Malley methodology was used for this narrative review. CINHAL, EMBASE, Medline, PsychInfo, Scopus, Web of Science, as well as grey literature, were searched from 2003 to April 2017. Two reviewers screened titles and abstracts for relevance to the review, and content analysis summarised the study findings. A total of 14 citations were included in the final review. Findings Exercise-based interventions targeted at the cervical spine appear most beneficial for adults with chronic whiplash-associated disorder (WAD). Invasive interventions still require more rigorous studies to deem their effectiveness for this population. Conclusion Further research is required to investigate and determine clinically relevant results for cervical spine intervention in patients with chronic WAD. PMID:29719724

Who benefits most from THC:CBD spray? Learning from clinical experience.

PubMed

Koehler, Jürgen

2014-01-01

Patients with multiple sclerosis (MS) represent a diverse and heterogeneous population varying in terms of disease type, its severity and variable progression/time-course, and with regard to the wide range of presenting symptoms. Consequently, detailed experience with individual patients is important to provide examples of therapy to specific patient types. In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) in patients with moderate to severe spasticity resistant to usual therapy will be presented. Three common clinical scenarios will be considered: MS patients with resistance to usual spasticity therapies; patients with impairment in MS spasticity symptoms; MS patients with relevant impairment in quality of life/activities of daily living (QoL/ADL). These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC:CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies, within the frame of use approved after large clinical trial results. Perhaps the most important finding is the possibility of obtaining relevant improvements in QoL/ADL in some patients with resistant MS spasticity, allowing them to engage back in physical and social activities. © 2014 S. Karger AG, Basel.

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

PubMed Central

Leibson, Tom; Carls, Alexandra; Ito, Shinya; Koren, Gideon

2016-01-01

Background Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. Methods and Findings Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. Conclusion This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications. PMID:27802281

Adolescent idiopathic scoliosis screening for school, community, and clinical health promotion practice utilizing the PRECEDE-PROCEED model

PubMed Central

Mirtz, Timothy A; Thompson, Mark A; Greene, Leon; Wyatt, Lawrence A; Akagi, Cynthia G

2005-01-01

Background Screening for adolescent idiopathic scoliosis (AIS) is a commonly performed procedure for school children during the high risk years. The PRECEDE-PROCEDE (PP) model is a health promotion planning model that has not been utilized for the clinical diagnosis of AIS. The purpose of this research is to study AIS in the school age population using the PP model and its relevance for community, school, and clinical health promotion. Methods MEDLINE was utilized to locate AIS data. Studies were screened for relevance and applicability under the auspices of the PP model. Where data was unavailable, expert opinion was utilized based on consensus. Results The social assessment of quality of life is limited with few studies approaching the long-term effects of AIS. Epidemiologically, AIS is the most common form of scoliosis and leading orthopedic problem in children. Behavioral/environmental studies focus on discovering etiologic relationships yet this data is confounded because AIS is not a behavioral. Illness and parenting health behaviors can be appreciated. The educational diagnosis is confounded because AIS is an orthopedic disorder and not behavioral. The administration/policy diagnosis is hindered in that scoliosis screening programs are not considered cost-effective. Policies are determined in some schools because 26 states mandate school scoliosis screening. There exists potential error with the Adam's test. The most widely used measure in the PP model, the Health Belief Model, has not been utilized in any AIS research. Conclusion The PP model is a useful tool for a comprehensive study of a particular health concern. This research showed where gaps in AIS research exist suggesting that there may be problems to the implementation of school screening. Until research disparities are filled, implementation of AIS screening by school, community, and clinical health promotion will be compromised. Lack of data and perceived importance by school/community health planners may influence clinical health promotion practices. PMID:16318632

Representation of Time-Relevant Common Data Elements in the Cancer Data Standards Repository: Statistical Evaluation of an Ontological Approach

PubMed Central

Chen, Henry W; Du, Jingcheng; Song, Hsing-Yi; Liu, Xiangyu; Jiang, Guoqian

2018-01-01

Background Today, there is an increasing need to centralize and standardize electronic health data within clinical research as the volume of data continues to balloon. Domain-specific common data elements (CDEs) are emerging as a standard approach to clinical research data capturing and reporting. Recent efforts to standardize clinical study CDEs have been of great benefit in facilitating data integration and data sharing. The importance of the temporal dimension of clinical research studies has been well recognized; however, very few studies have focused on the formal representation of temporal constraints and temporal relationships within clinical research data in the biomedical research community. In particular, temporal information can be extremely powerful to enable high-quality cancer research. Objective The objective of the study was to develop and evaluate an ontological approach to represent the temporal aspects of cancer study CDEs. Methods We used CDEs recorded in the National Cancer Institute (NCI) Cancer Data Standards Repository (caDSR) and created a CDE parser to extract time-relevant CDEs from the caDSR. Using the Web Ontology Language (OWL)–based Time Event Ontology (TEO), we manually derived representative patterns to semantically model the temporal components of the CDEs using an observing set of randomly selected time-related CDEs (n=600) to create a set of TEO ontological representation patterns. In evaluating TEO’s ability to represent the temporal components of the CDEs, this set of representation patterns was tested against two test sets of randomly selected time-related CDEs (n=425). Results It was found that 94.2% (801/850) of the CDEs in the test sets could be represented by the TEO representation patterns. Conclusions In conclusion, TEO is a good ontological model for representing the temporal components of the CDEs recorded in caDSR. Our representative model can harness the Semantic Web reasoning and inferencing functionalities and present a means for temporal CDEs to be machine-readable, streamlining meaningful searches. PMID:29472179

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.

PubMed

Pariente, Gali; Leibson, Tom; Carls, Alexandra; Adams-Webber, Thomasin; Ito, Shinya; Koren, Gideon

2016-11-01

Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.

Computer vision syndrome-A common cause of unexplained visual symptoms in the modern era.

PubMed

Munshi, Sunil; Varghese, Ashley; Dhar-Munshi, Sushma

2017-07-01

The aim of this study was to assess the evidence and available literature on the clinical, pathogenetic, prognostic and therapeutic aspects of Computer vision syndrome. Information was collected from Medline, Embase & National Library of Medicine over the last 30 years up to March 2016. The bibliographies of relevant articles were searched for additional references. Patients with Computer vision syndrome present to a variety of different specialists, including General Practitioners, Neurologists, Stroke physicians and Ophthalmologists. While the condition is common, there is a poor awareness in the public and among health professionals. Recognising this condition in the clinic or in emergency situations like the TIA clinic is crucial. The implications are potentially huge in view of the extensive and widespread use of computers and visual display units. Greater public awareness of Computer vision syndrome and education of health professionals is vital. Preventive strategies should form part of work place ergonomics routinely. Prompt and correct recognition is important to allow management and avoid unnecessary treatments. © 2017 John Wiley & Sons Ltd.

Autosomal dominant polycystic kidney disease in children

PubMed Central

Cadnapaphornchai, Melissa A.

2015-01-01

Purpose of review Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting one in 500 individuals. The cardinal manifestation of ADPKD is progressive cystic dilatation of renal tubules with kidney enlargement and progression to end-stage renal disease in approximately half of cases by 60 years of age. Although previously considered a condition of adults, it is clear that children and young adults are subject to the complications of ADPKD. Recent findings It has been increasingly recognized that interventions early in life are necessary in order to confer the best long-term outcome in this common condition. Therefore, it is imperative for pediatricians to recognize the manifestations and complications of this disease. Until recently ADPKD management focused on general principles of chronic kidney disease. However, several recent clinical trials in children and adults with ADPKD have focused on disease-specific therapies. Summary This review will highlight the clinical manifestations, diagnosis, and appropriate management of ADPKD in childhood and will review recent relevant clinical trials in children and adults with this condition. PMID:25635587

Fundamentals in Biostatistics for Investigation in Pediatric Dentistry: Part II -Biostatistical Methods.

PubMed

Pozos-Guillén, Amaury; Ruiz-Rodríguez, Socorro; Garrocho-Rangel, Arturo

The main purpose of the second part of this series was to provide the reader with some basic aspects of the most common biostatistical methods employed in health sciences, in order to better understand the validity, significance and reliability of the results from any article on Pediatric Dentistry. Currently, as mentioned in the first paper, Pediatric Dentists need basic biostatistical knowledge to be able to apply it when critically appraise a dental article during the Evidence-based Dentistry (EBD) process, or when participating in the development of a clinical study with dental pediatric patients. The EBD process provides a systematic approach of collecting, review and analyze current and relevant published evidence about oral health care in order to answer a particular clinical question; then this evidence should be applied in everyday practice. This second report describes the most commonly used statistical methods for analyzing and interpret collected data, and the methodological criteria to be considered when choosing the most appropriate tests for a specific study. These are available to Pediatric Dentistry practicants interested in reading or designing original clinical or epidemiological studies.

Decision Support Tools for Clinical Diagnosis of Disease in Cows with Suspected Bovine Spongiform Encephalopathy

PubMed Central

Saegerman, C.; Speybroeck, N.; Roels, S.; Vanopdenbosch, E.; Thiry, E.; Berkvens, D.

2004-01-01

Reporting of clinically suspected cattle is currently the most common method for detecting cases of bovine spongiform encephalopathy (BSE). Improvement of clinical diagnosis and decision-making remains crucial. A comparison of clinical patterns, consisting of 25 signs, was made between all 30 BSE cases, confirmed in Belgium before October 2002, and 272 suspected cases that were subsequently determined to be histologically, immunohistochemically, and scrapie-associated-fiber negative. Seasonality in reporting suspected cases was observed, with more cases being reported during wintertime when animals were kept indoors. The median duration of illness was 30 days. The 10 most relevant signs of BSE were kicking in the milking parlor, hypersensitivity to touch and/or sound, head shyness, panic-stricken response, reluctance to enter in the milking parlor, abnormal ear movement or carriage, increased alertness behavior, reduced milk yield, teeth grinding, and temperament change. Ataxia did not appear to be a specific sign of BSE. A classification and regression tree was constructed by using the following four features: age of the animal, year of birth, number of relevant BSE signs noted, and number of clinical signs, typical for listeriosis, noted. The model had a sensitivity of 100% and a specificity of 85%. This approach allows the use of an interactive decision-support tool, based entirely on odds ratios, a statistic independent of disease prevalence. PMID:14715749

Comparing deep learning and concept extraction based methods for patient phenotyping from clinical narratives.

PubMed

Gehrmann, Sebastian; Dernoncourt, Franck; Li, Yeran; Carlson, Eric T; Wu, Joy T; Welt, Jonathan; Foote, John; Moseley, Edward T; Grant, David W; Tyler, Patrick D; Celi, Leo A

2018-01-01

In secondary analysis of electronic health records, a crucial task consists in correctly identifying the patient cohort under investigation. In many cases, the most valuable and relevant information for an accurate classification of medical conditions exist only in clinical narratives. Therefore, it is necessary to use natural language processing (NLP) techniques to extract and evaluate these narratives. The most commonly used approach to this problem relies on extracting a number of clinician-defined medical concepts from text and using machine learning techniques to identify whether a particular patient has a certain condition. However, recent advances in deep learning and NLP enable models to learn a rich representation of (medical) language. Convolutional neural networks (CNN) for text classification can augment the existing techniques by leveraging the representation of language to learn which phrases in a text are relevant for a given medical condition. In this work, we compare concept extraction based methods with CNNs and other commonly used models in NLP in ten phenotyping tasks using 1,610 discharge summaries from the MIMIC-III database. We show that CNNs outperform concept extraction based methods in almost all of the tasks, with an improvement in F1-score of up to 26 and up to 7 percentage points in area under the ROC curve (AUC). We additionally assess the interpretability of both approaches by presenting and evaluating methods that calculate and extract the most salient phrases for a prediction. The results indicate that CNNs are a valid alternative to existing approaches in patient phenotyping and cohort identification, and should be further investigated. Moreover, the deep learning approach presented in this paper can be used to assist clinicians during chart review or support the extraction of billing codes from text by identifying and highlighting relevant phrases for various medical conditions.

Molecular Subtypes of Glioblastoma Are Relevant to Lower Grade Glioma

PubMed Central

Sloan, Andrew E.; Chen, Yanwen; Brat, Daniel J.; O’Neill, Brian Patrick; de Groot, John; Yust-Katz, Shlomit; Yung, Wai-Kwan Alfred; Cohen, Mark L.; Aldape, Kenneth D.; Rosenfeld, Steven; Verhaak, Roeland G. W.; Barnholtz-Sloan, Jill S.

2014-01-01

Background Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). Methods Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al. Results Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs. Conclusions GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression. PMID:24614622

Analysis of legal high materials by ultra-performance liquid chromatography with time of flight mass spectrometry as part of a toxicology vigilance system: what are the most popular novel psychoactive substances in the UK?

PubMed

Ford, Loretta T; Berg, Jonathan D

2017-03-01

Introduction Legal highs also known as novel psychoactive substances mimic the effects of classic drugs of abuse. Challenges to developing screening services for novel psychoactive substances include identifying which novel psychoactive substances are available to target. Using new techniques such as exact mass time of flight can help identify common novel psychoactive substances to target for screening patient samples by routine methods such as tandem mass spectrometry. We demonstrate this strategy working in our own clinical toxicology laboratory after qualitative analysis of 98 suspect materials for novel psychoactive substances by ultra-performance liquid chromatography with time of flight mass spectrometry. Results From July 2014 to July 2015 we received 98 requests to test a range of different suspect materials for novel psychoactive substances including herbs, tobacco, liquids, pills and powders. Overall, 87% of the suspect materials tested positive for novel psychoactive substances, and 15% for controlled drugs. Three common novel psychoactive substances were present in 74% of the suspect materials: methiopropamine, a methamphetamine analogue; ethylphenidate, a cocaine mimic; and the third generation synthetic cannabinoid 5F-AKB-48. For the 55 branded products we tested only 24% of the stated contents matched exactly the compounds we detected. Conclusion Testing suspect materials using ultra-performance liquid chromatography with time of flight mass spectrometry has identified three common novel psychoactive substances in use in the UK, simplifying the development of a relevant novel psychoactive substances screening service to our population. By incorporating this into our routine liquid chromatography tandem mass spectrometry drugs of abuse screen, then offers a clinically relevant novel psychoactive substances service to our users. This strategy ensures our clinical toxicology service continues to remain effective to meet the challenges of the changing drug use in the UK.

Patch testing in children from 2005 to 2012: results from the North American contact dermatitis group.

PubMed

Zug, Kathryn A; Pham, Anh Khoa; Belsito, Donald V; DeKoven, Joel G; DeLeo, Vincent A; Fowler, Joseph F; Fransway, Anthony F; Maibach, Howard I; Marks, James G; Mathias, C G Toby; Pratt, Melanie D; Sasseville, Denis; Storrs, Frances J; Taylor, James S; Warshaw, Erin M; Zirwas, Matthew J

2014-01-01

Allergic contact dermatitis is common in children. Epicutaneous patch testing is an important tool for identifying responsible allergens. The objective of this study was to provide the patch test results from children (aged ≤18 years) examined by the North American Contact Dermatitis Group from 2005 to 2012. This is a retrospective analysis of children patch-tested with the North American Contact Dermatitis Group 65- or 70-allergen series. Frequencies and counts were compared with previously published data (2001-2004) using χ statistics. A total of 883 children were tested during the study period. A percentage of 62.3% had ≥1 positive patch test and 56.7% had ≥1 relevant positive patch test. Frequencies of positive patch test and relevant positive patch test reaction were highest with nickel sulfate (28.1/25.6), cobalt chloride (12.3/9.1), neomycin sulfate (7.1/6.6), balsam of Peru (5.7/5.5), and lanolin alcohol 50% petrolatum vehicle (5.5/5.1). The ≥1 positive patch test and ≥1 relevant positive patch test in the children did not differ significantly from adults (≥19 years) or from previously tested children (2001-2004). The percentage of clinically relevant positive patch tests for 27 allergens differed significantly between the children and adults. A total of 23.6% of children had a relevant positive reaction to at least 1 supplemental allergen. Differences in positive patch test and relevant positive patch test frequencies between children and adults as well as test periods confirm the importance of reporting periodic updates of patch testing in children to enhance clinicians' vigilance to clinically important allergens.

Steroid-induced hyperglycaemia in hospitalised patients: does it matter?

PubMed

Cheung, N Wah

2016-12-01

Steroid-induced hyperglycaemia is a common problem faced by endocrinologists in hospital wards. In this issue of Diabetologia, Popovic and colleagues (DOI 10.1007/s00125-016-4091-4 ) have conducted a subanalysis within a randomised controlled trial of prednisone therapy for community-acquired pneumonia. The authors found that the presence of diabetes or hyperglycaemia related to steroid therapy did not attenuate the clinical benefits of steroid therapy. The relevance and possible implications of these findings are discussed.

MRI brain imaging.

PubMed

Skinner, Sarah

2013-11-01

General practitioners (GPs) are expected to be allowed to request MRI scans for adults for selected clinically appropriate indications from November 2013 as part of the expansion of Medicare-funded MRI services announced by the Federal Government in 2011. This article aims to give a brief overview of MRI brain imaging relevant to GPs, which will facilitate explanation of scan findings and management planning with their patients. Basic imaging techniques, common findings and terminology are presented using some illustrative case examples.

Time to connect: bringing social context into addiction neuroscience

PubMed Central

Heilig, Markus; Epstein, David H.; Nader, Michael A.; Shaham, Yavin

2017-01-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant. PMID:27277868

The abstinence phobias: links between substance abuse and anxiety.

PubMed

Hall, S M

1984-09-01

This paper presents a new model to explain the observed relationship between anxiety and substance abuse. Specifically, the concept of "abstinence phobias," common across psychoactive substances, is developed. The evidence needed to support this concept is outlined, and relevant data from studies of opiate, alcohol, and tobacco dependences are reviewed. Parallel data obtained from the treatment of obesity are discussed. It is concluded that the abstinence phobia merits further study; clinical implications are also considered.

Time to connect: bringing social context into addiction neuroscience.

PubMed

Heilig, Markus; Epstein, David H; Nader, Michael A; Shaham, Yavin

2016-09-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

Yellow dots in trichoscopy: relevance, clinical significance and peculiarities*

PubMed Central

Lima, Caren dos Santos; Lemes, Luciana Rodino; Melo, Daniel Fernandes

2017-01-01

Yellow dots are follicular ostium filled with keratin and/or sebum. Initially, they were exclusively associated with alopecia areata. Currently they have also been described in androgenetic alopecia, chronic cutaneous (discoid) lupus erythematosus, and dissecting cellulitis. Due to the growing importance of trichoscopy and its findings in the evaluation of the scalp, this article describes the main diseases in which yellow dots are a common trichoscopic finding, highlighting its characteristics in each dermatosis. PMID:29166518

Dysphagia and dentistry.

PubMed

Curl, Charlotte; Boyle, Carole

2014-06-01

Dysphagia is defined as a 'difficulty in swallowing' and is commonly found in the general population, particularly in the elderly. This article gives an overview of the more frequently encountered swallowing disorders and provides advice on how to manage the dysphagic patient in the dental surgery. Clinical Relevance: By identifying patients with dysphagia and being aware of the potential problems that the clinician may experience when treating them, the risk of aspiration, choking and healthcare-acquired upper respiratory tract infections may be reduced.

Prevalence of sensitization to the predatory mite Amblyseius cucumeris as a new occupational allergen in horticulture.

PubMed

Groenewoud, G C M; de Graaf in 't Veld, C; vVan Oorschot-van Nes, A J; de Jong, N W; Vermeulen, A M; van Toorenenbergen, A W; Burdorf, A; de Groot, H; Gerth van Wijk, R

2002-07-01

Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyzeius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied. Four hundred and seventytwo employees were asked to fill in a questionnaire and were tested on location. Next to RAST, skin prick tests (SPTs) were performed with common inhalant allergens, the storage mite Tyrophagus putrescentiae (Tp) which serves as a temporary food source during the cultivation process and Ac. Furthermore, nasal challenge tests with Ac were carried out in 23 sensitized employees. SPTs positive to Ac were found in 109 employees (23%). Work-related symptoms were reported by 76.1%. Sensitization to Tp was found in 62 employees of whom 48 were also sensitized to Ac. Immunoglobulin (Ig)E-mediated allergy to inhalant allergens appeared to be an important risk factor for sensitization to Ac. Employees with rhinitis symptoms showed a significantly higher response to all Ac doses during the nasal challenge test compared with employees without rhinitis symptoms. The predatory mite Ac is a new occupational allergen in horticulture which can cause an IgE-mediated allergy in exposed employees. It is biologically active on the mucous membranes of the nose and therefore clinically relevant for the development of work-related symptoms.

The challenge of preoperative quantification of functional tricuspid regurgitation and of right ventricle function: what information is clinically relevant?

PubMed

Hahn, Rebecca T

2017-10-01

Functional or secondary tricuspid regurgitation (TR) is the most common etiology of severe TR in the western world. The presence of functional TR, either isolated or in combination with left heart disease is associated with unfavorable natural history however surgical mortality for isolated tricuspid valve interventions remain higher than for any other single valve surgery. Determining the severity of TR remains a controversial area and will continue to evolve as new techniques for assessing this valve as well as the right ventricle, are investigated. The following review will describe tricuspid anatomy, define echocardiographic views for evaluating tricuspid valve and right heart morphology and function, that are relevant to the pre-procedural assessment of functional TR.

A clinical decision support system for diagnosis of Allergic Rhinitis based on intradermal skin tests.

PubMed

Jabez Christopher, J; Khanna Nehemiah, H; Kannan, A

2015-10-01

Allergic Rhinitis is a universal common disease, especially in populated cities and urban areas. Diagnosis and treatment of Allergic Rhinitis will improve the quality of life of allergic patients. Though skin tests remain the gold standard test for diagnosis of allergic disorders, clinical experts are required for accurate interpretation of test outcomes. This work presents a clinical decision support system (CDSS) to assist junior clinicians in the diagnosis of Allergic Rhinitis. Intradermal Skin tests were performed on patients who had plausible allergic symptoms. Based on patient׳s history, 40 clinically relevant allergens were tested. 872 patients who had allergic symptoms were considered for this study. The rule based classification approach and the clinical test results were used to develop and validate the CDSS. Clinical relevance of the CDSS was compared with the Score for Allergic Rhinitis (SFAR). Tests were conducted for junior clinicians to assess their diagnostic capability in the absence of an expert. The class based Association rule generation approach provides a concise set of rules that is further validated by clinical experts. The interpretations of the experts are considered as the gold standard. The CDSS diagnoses the presence or absence of rhinitis with an accuracy of 88.31%. The allergy specialist and the junior clinicians prefer the rule based approach for its comprehendible knowledge model. The Clinical Decision Support Systems with rule based classification approach assists junior doctors and clinicians in the diagnosis of Allergic Rhinitis to make reliable decisions based on the reports of intradermal skin tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

PubMed

Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

2017-01-01

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Update in outpatient general internal medicine: practice-changing evidence published in 2014.

PubMed

Sundsted, Karna K; Wieland, Mark L; Szostek, Jason H; Post, Jason A; Mauck, Karen F

2015-10-01

The practice of outpatient general internal medicine requires a diverse and evolving knowledge base. General internists must identify practice-changing shifts in the literature and reflect on their impact. Accordingly, we conducted a review of practice-changing articles published in outpatient general internal medicine in 2014. To identify high-quality, clinically relevant publications, we reviewed all titles and abstracts published in the following primary data sources in 2014: New England Journal of Medicine, Journal of the American Medical Association (JAMA), Annals of Internal Medicine, JAMA Internal Medicine, and the Cochrane Database of Systematic Reviews. All 2014 primary data summaries from Journal Watch-General Internal Medicine and ACP JournalWise also were reviewed. The authors used a modified Delphi method to reach consensus on inclusion of 8 articles using the following criteria: clinical relevance to outpatient internal medicine, potential for practice change, and strength of evidence. Clusters of important articles around one clinical question were considered as a single-candidate series. The article merits were debated until consensus was reached on the final 8, spanning a variety of topics commonly encountered in outpatient general internal medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

PubMed Central

Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance.

PubMed

Fernández-Vega, Iván; Santos-Juanes, Jorge; Camacho-Urkaray, Emma; Lorente-Gea, Laura; García, Beatriz; Gutiérrez-Corres, Francisco Borja; Quirós, Luis M; Guerra-Merino, Isabel; Aguirre, José Javier

2018-02-12

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

PubMed

Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring

2018-02-01

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

Influenza Vaccination in Patients with Common Variable Immunodeficiency (CVID).

PubMed

Mieves, Jan F; Wittke, Kirsten; Freitag, Helma; Volk, Hans-Dieter; Scheibenbogen, Carmen; Hanitsch, Leif G

2017-10-05

Vaccination against influenza in patients with primary antibody deficiency is recommended. Common variable immunodeficiency (CVID) is the most frequent and clinically relevant antibody deficiency disease and is by definition characterized by an impaired vaccination response. The purpose of this review is to present the current knowledge of humoral and cellular vaccine response to influenza in CVID patients. Studies conducted in CVID patients demonstrated an impaired humoral response upon influenza vaccination. Data on cellular immune response are in part conflicting, with two out of three studies showing responses similar to healthy controls. Available data suggest a benefit from influenza vaccination in CVID patients. Therefore, annual influenza vaccination in patients and their close household contacts is recommended.

[Managment of acute low back pain without trauma - an algorithm].

PubMed

Melcher, Carolin; Wegener, Bernd; Jansson, Volkmar; Mutschler, Wolf; Kanz, Karl-Georg; Birkenmaier, Christof

2018-05-14

Low back pain is a common problem for primary care providers, outpatient clinics and A&E departments. The predominant symptoms are those of so-called "unspecific back pain", but serious pathologies can be concealed by the clinical signs. Especially less experienced colleagues have problems in treating these patients, as - despite the multitude of recommendations and guidelines - there is no generally accepted algorithm. After a literature search (Medline/Cochrane), 158 articles were selected from 15,000 papers and classified according to their level of evidence. These were attuned to the clinical guidelines of the orthopaedic and pain-physician associations in Europe, North America and overseas and the experience of specialists at LMU Munich, in order to achieve consistency with literature recommendations, as well as feasibility in everyday clinical work and optimised with practical relevance. An algorithm was formed to provide the crucial differential diagnosis of lumbar back pain according to its clinical relevance and to provide a plan of action offering reasonable diagnostic and therapeutic steps. As a consequence of distinct binary decisions, low back patients should be treated at any given time according to the guidelines, with emergencies detected, unnecessary diagnostic testing and interventions averted and reasonable treatment initiated pursuant to the underlying pathology. In the context of the available evidence, a clinical algorithm has been developed that translates the complex diagnostic testing of acute low back pain into a transparent, structured and systematic guideline. Georg Thieme Verlag KG Stuttgart · New York.

Variation of clinical outcomes used in glaucoma randomised controlled trials: a systematic review.

PubMed

Ismail, Rehab; Azuara-Blanco, Augusto; Ramsay, Craig R

2014-04-01

In randomised clinical trials (RCTs) the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. The purpose of this review is to identify different clinical outcomes reported in glaucoma trials. We conducted a systematic review of glaucoma RCTs. A sample or selection of glaucoma trials were included bounded by a time frame (between 2006 and March 2012). Only studies in English language were considered. All clinical measured and reported outcomes were included. The possible variations of clinical outcomes were defined prior to data analysis. Information on reported clinical outcomes was tabulated and analysed using descriptive statistics. Other data recorded included type of intervention and glaucoma, duration of the study, defined primary outcomes, and outcomes used for sample size calculation, if nominated. The search strategy identified 4323 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%). There is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

Assessing the prevalence and clinical relevance of positive abdominal and pelvic CT findings in senior patients presenting to the emergency department.

PubMed

Alabousi, Abdullah; Patlas, Michael N; Meshki, Malek; Monteiro, Sandra; Katz, Douglas S

2016-04-01

The purpose of our study was to retrospectively evaluate the prevalence and clinical relevance of positive abdominal and pelvic CT findings for patients 65 years of age and older, when compared with all other scanned adult Emergency Department (ED) patients, at a single tertiary care hospital. Our hypothesis was that there is an increased prevalence and clinical relevance of positive abdominal/pelvic CT findings in senior patients. A research ethics board-approved retrospective review of all adult patients who underwent an emergency CT of the abdomen and pelvis for acute nontraumatic abdominal and/or pelvic signs and symptoms was performed. Two thousand one hundred two patients between October 1, 2011, and September 30, 2013, were reviewed. Six hundred thirty-one patients were included in the <65 group (298 men and 333 women; mean age 46, age range 18-64), and 462 were included in the >65 group (209 men and 253 women; mean age 77.6, age range 65-99). Overall, there were more positive CT findings for patients <65 (389 positive cases, 61.6 %) compared with the >65 group (257 positive cases, 55.6 %), which was a statistically significant difference (p < 0.03). Moreover, with the exception of complicated appendicitis cases, which were more common in the >65 group, there were no statistically significant differences in the clinical/surgical relevance of the positive CT findings between the two groups. The findings of our retrospective study therefore refute our hypothesis that there is an increased prevalence of positive abdominal CT findings in patients >65. This may be related to ED physicians at our institution being more hesitant to order CT examinations for the younger population, presumably due to radiation concerns. However, older patients in our series were more likely to present with complicated appendicitis, and a lower threshold for ordering CT examinations of the abdomen and pelvis in this patient population should therefore be considered.

[Blastocystis spp.: Advances, controversies and future challenges].

PubMed

Del Coco, Valeria F; Molina, Nora B; Basualdo, Juan A; Córdoba, María A

Blastocystis spp. is the most common protozoan detected in human stool samples. In developing countries, infection rates are higher than 20%. The presence of this parasite in the feces of several host species suggests its zoonotic potential. The clinical relevance and the pathogenic role of Blastocystis spp. in the intestinal tract remain unclear. There are several clinical reports that recognize it as the etiologic agent of several intestinal disorders such as diarrhea, inflammatory bowel disease and ulcerative colitis, although the pathogenicity of this parasite has not been proved yet. This wide range of clinical manifestations could be related to the genetic diversity exhibited by this parasite. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Consensus and contentious statements on the use of probiotics in clinical practice: a South East Asian Gastro-neuro Motility Association Working Team Report.

PubMed

Gwee, Kok-Ann; Lee, Warren Wei-Rhen; Ling, Khoon Lin; Ooi, Choon Jin; Quak, Seng Hock; Dan, Yock Young; Siah, Kewin Tien-Ho; Huang, James Guoxian; Chua, Andrew Seng Boon; Hilmi, Ida Normiha; Raja Affendi, R A; Ong, Christina; Simadibrata, Marcellus; Abdullah, Murdani; Sollano, Jose D; Leelakusolvong, Somchai; Gonlachanvit, Sutep; Lee, Yeong Yeh; Ricaforte-Campos, Jane D; Yin, Yee Kian; Chong, Kuck-Meng; Wong, Chong Yuen

2018-04-26

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much traction, giving rise to an abundance of medical claims, and of health supplements. We identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics, and importantly their limitations. This article is protected by copyright. All rights reserved.

Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study.

PubMed

Keizer, D; van Wijhe, M; Post, W J; Uges, D R A; Wierda, J M K H

2007-08-01

Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with pain thresholds obtained with quantitative sensory testing. During a 4-week trial, we administered a cannabis extract to 17 patients with allodynia. We quantified the severity of the allodynia with Von Frey monofilaments before, during and after the patients finished the trial. We also asked the patients to rate their pain on a numeric rating scale at these three moments. We found that most of the effect of the cannabis occurred in the last 2 weeks of the trial. In this phase, we observed that the pain thresholds, as measured with Von Frey monofilaments, were inversely correlated with a decrease of the perceived pain intensity. These preliminary findings indicate clinical relevance of quantitative sensory testing with Von Frey monofilaments in the quantification of allodynia in patients with neuropathic pain, although confirmation of our data is still required in further studies to position this method of quantitative sensory testing as a valuable tool, for example, in the evaluation of therapeutic interventions for neuropathic pain.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

PubMed

Dorgalaleh, Akbar; Alavi, Sayed Ezatolla Rafiee; Tabibian, Shadi; Soori, Shahrzad; Moradi, Es'hagh; Bamedi, Taregh; Asadi, Mansour; Jalalvand, Masumeh; Shamsizadeh, Morteza

2017-05-01

Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. For this study, all relevant publications were searched in Medlin until 2015. Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

Computed tomographic findings in dogs and cats with temporomandibular joint disorders: 58 cases (2006–2011)

PubMed Central

Arzi, Boaz; Cissell, Derek D.; Verstraete, Frank J. M.; Kass, Philip H.; DuRaine, Grayson D.; Athanasiou, Kyriacos A.

2013-01-01

Objective To describe CT findings in dogs and cats with temporomandibular joint (TMJ) disorders. Design Retrospective case-series. Animals 41 dogs and 17 cats. Procedures Medical records and CT images of the skull were reviewed for dogs and cats that were examined at a dentistry and oral surgery specialty practice between 2006 and 2011. Results Of 142 dogs and 42 cats evaluated, 41 dogs and 17 cats had CT findings consistent with a TMJ disorder. In dogs, the most common TMJ disorder was osteoarthritis; however, in most cases, there were other TMJ disorders present in addition to osteoarthritis. Osteoarthritis was more frequently identified at the medial aspect rather than the lateral aspect of the TMJ, whereas the frequency of osteoarthritic involvement of the dorsal and ventral compartments did not differ significantly. In cats, fractures were the most common TMJ disorder, followed by osteoarthritis. Clinical signs were observed in all dogs and cats with TMJ fractures, dysplasia, ankylosis, luxation, and tumors; however, only 4 of 15 dogs and 2 of 4 cats with osteoarthritis alone had clinical signs. Conclusions and Clinical Relevance Results indicated that TMJ disorders are frequently present in combination. Osteoarthritis was the most common TMJ disorder in dogs and the second most common TMJ disorder in cats. Computed tomography should be considered as a tool for the diagnosis of TMJ disorders in dogs and cats with suspected orofacial disorders and pain. PMID:23234284

Concordant parent-child reports of anxiety predict impairment in youth with functional abdominal pain

PubMed Central

Cunningham, Natoshia Raishevich; Cohen, Mitchell B.; Farrell, Michael K.; Mezoff, Adam G.; Lynch-Jordan, Anne; Kashikar-Zuck, Susmita

2014-01-01

Introduction Functional abdominal pain (FAP) is associated with significant anxiety and impairment. Prior investigations of child anxiety in youth with FAP are generally limited by small sample sizes, based on child report, and use lengthy diagnostic tools. It is unknown 1) if a brief anxiety screening tool is feasible, 2) whether parent and child reports of anxiety are congruent, and 3) whether parent and child agreement of child anxiety corresponds to increased impairment. The purpose of this investigation was to examine anxiety characteristics in youth with FAP using parent and child reports. Parent-child agreement of child anxiety symptoms was examined in relation to pain and disability. Materials and Methods One-hundred patients with FAP (8-18 years of age) recruited from pediatric gastroenterology clinics completed measures of pain intensity (Numeric Rating Scale), and disability (Functional Disability Inventory). Patients and caregivers both completed a measure of child anxiety characteristics (Screen for Child Anxiety and Related Disorders). Results Clinically significant anxiety symptoms were more commonly reported by youth (54%) than their parents (30%). Panic/somatic symptoms, generalized anxiety, and separation anxiety were most commonly endorsed by patients whereas generalized anxiety, separation anxiety, and school avoidance were most commonly reported by parents. The majority (65%) of parents and children agreed on presence (26%) or absence (39%) of clinically significant anxiety. Parent-child agreement of clinically significant anxiety was related to increased impairment. Discussion A brief screening instrument of parent and child reports of anxiety can provide clinically relevant information for comprehensive treatment planning in children with FAP. PMID:25714575

Orthotic management of the neuropathic foot: an interdisciplinary care perspective.

PubMed

Robinson, Christopher; Major, Matthew J; Kuffel, Charles; Hines, Kevin; Cole, Pamela

2015-02-01

Clinical management of the patient with neuropathic foot is becoming commonplace in orthotic clinics worldwide. The presentations that can result from neuropathic foot are diverse, requiring clinicians to understand the pathomechanics of ulceration, infection, and Charcot joint arthropathy to provide effective interventions. The purpose of this clinical perspective is to provide a review of the literature regarding clinical concepts associated with orthotic management of neuropathic foot. Literature review and clinical case study. Relevant literature were reviewed and summarized, and a clinical case study synthesizing reviewed concepts was presented. Given the multifactorial nature of the neuropathic foot, treatments must be multifaceted and patient-specific to effectively address the underlying disease processes. While systemic issues such as peripheral arterial disease are treated by physicians, local issues such as foot deformity are managed by orthotists. Orthotic interventions commonly include custom footwear to reduce the risk of ulceration through creation of a protective environment or targeted plantar offloading. Patient and caregiver education to encourage management compliance is equally as important to ensure successful treatment. Patients with neuropathic foot benefit from an interdisciplinary care approach which engages physicians, wound care practitioners, and orthotists to treat and manage systemic and local problems. Addressing this pathology through interdisciplinary care may positively affect the patient's health status while lowering associated healthcare costs through improved treatment efficacy. The commonality of neuropathic foot and associated complications including ulceration, infection, and Charcot joint arthropathy requires that the patient care team have a fundamental understanding of these pathologies and common treatment modalities. We review orthotic treatment modalities to assist clinicians with the management of patients with neuropathic foot. © The International Society for Prosthetics and Orthotics 2014.

Academic medical centers as innovation ecosystems to address population -omics challenges in precision medicine.

PubMed

Silva, Patrick J; Schaibley, Valerie M; Ramos, Kenneth S

2018-02-15

While the promise of the Human Genome Project provided significant insights into the structure of the human genome, the complexities of disease at the individual level have made it difficult to utilize -omic information in clinical decision making. Some of the existing constraints have been minimized by technological advancements that have reduced the cost of sequencing to a rate far in excess of Moore's Law (a halving in cost per unit output every 18 months). The reduction in sequencing costs has made it economically feasible to create large data commons capturing the diversity of disease across populations. Until recently, these data have primarily been consumed in clinical research, but now increasingly being considered in clinical decision- making. Such advances are disrupting common diagnostic business models around which academic medical centers (AMCs) and molecular diagnostic companies have collaborated over the last decade. Proprietary biomarkers and patents on proprietary diagnostic content are no longer driving biomarker collaborations between industry and AMCs. Increasingly the scope of the data commons and biorepositories that AMCs can assemble through a nexus of academic and pharma collaborations is driving a virtuous cycle of precision medicine capabilities that make an AMC relevant and highly competitive. A rebalancing of proprietary strategies and open innovation strategies is warranted to enable institutional precision medicine asset portfolios. The scope of the AMC's clinical trial and research collaboration portfolios with industry are increasingly dependent on the currency of data, and less on patents. Intrapeneurial support of internal service offerings, clinical trials and clinical laboratory services for example, will be important new points of emphasis at the academic-industry interface. Streamlining these new models of industry collaboration for AMCs are a new area for technology transfer offices to offer partnerships and to add value beyond the traditional intellectual property offering.

Public health relevance of drug-nutrition interactions.

PubMed

Péter, Szabolcs; Navis, Gerjan; de Borst, Martin H; von Schacky, Clemens; van Orten-Luiten, Anne Claire B; Zhernakova, Alexandra; Witkamp, Renger F; Janse, André; Weber, Peter; Bakker, Stephan J L; Eggersdorfer, Manfred

2017-08-01

The public health relevance of drug-nutrition interactions is currently highly undervalued and overlooked. This is particularly the case for elderly persons where multi-morbidity and consequently polypharmacy is very common. Vitamins and other micronutrients have central functions in metabolism, and their interactions with drugs may result in clinically relevant physiological impairments but possibly also in positive effects. On 12 April 2016, the University Medical Center Groningen (The Netherlands), as part of its Healthy Ageing program, organized a workshop on the public health relevance of drug-nutrient interactions. In this meeting, experts in the field presented results from recent studies on interactions between pharmaceuticals and nutrients, and discussed the role of nutrition for elderly, focusing on those persons receiving pharmaceutical treatment. This paper summarizes the proceedings of the symposium and provides an outlook for future research needs and public health measures. Since food, pharma and health are closely interconnected domains, awareness is needed in the medical community about the potential relevance of drug-nutrition interactions. Experts and stakeholders should advocate for the integration of drug-nutrition evaluations in the drug development process. Strategies for the individual patients should be developed, by installing drug review protocols, screening for malnutrition and integrating this topic into the general medical advice.

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

PubMed

Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

2010-07-01

Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

Seventeen Years of Using Flowable Resin Restoratives--A Dental Practitioner's Personal Clinical Review.

PubMed

Firla, Markus Th

2015-04-01

Seen through the author's eyes on the basis of his practising dentistry for almost three decades, light-activated flowable resin restoratives (FRCs) or, in common clinical dental terminology, flowable composites have gradually gained major importance in restorative dentistry. Inputs to this ongoing trend are coming from continuous improvements in material properties and the favourable handling characteristics experienced with this particular group of restoratives. Intended to be used in direct adhesive filling procedures, the number and variety of recent generations of flowable composites for lining, restoration of all cavity classes (I-V), core build-ups and, more recently, 'bulk-fill-restorations', however, necessitates a profound clinical understanding of the selective use of flowable composites to ensure clinical success and guarantee long-term high quality results. Clinical relevance: Today's flowable composites allow for reliable restoration of all kinds of defects. However, both the handling characteristics and the material properties of FRCs must be fully understood before taking advantage of their potentially excellent clinical performance.

Is Pain Intensity Really That Important to Assess in Chronic Pain Patients? A Study Based on the Swedish Quality Registry for Pain Rehabilitation (SQRP)

PubMed Central

Bromley Milton, Maria; Börsbo, Björn; Rovner, Graciela; Lundgren-Nilsson, Åsa; Stibrant-Sunnerhagen, Katharina; Gerdle, Björn

2013-01-01

Background Incorporating the patient's view on care and treatment has become increasingly important for health care. Patients describe the variety of consequences of their chronic pain conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of common symptoms in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. This study has three aims: 1) to determine the importance of different symptoms with respect to participation and ill-health; 2) to identify subgroups based on data concerning important symptoms; and 3) to determine the secondary consequences for the identified subgroups with respect to participation and health factors. Methods and Subjects This study is based on a cohort of patients referred to a multidisciplinary pain centre at a university hospital (n = 4645, participation rate 88%) in Sweden. The patients answered a number of questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish Quality Registry for Pain Rehabilitation (SQRP). Results Common symptoms (such as pain intensity, depression, and anxiety) in patients with chronic pain showed great variability across subjects and 60% of the cohort had normal values with respect to depressive and anxiety symptoms. Pain intensity more than psychological symptoms showed stronger relationships with participation and health. It was possible to identify subgroups based on pain intensity, depression, and anxiety. With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety. Conclusions Common symptoms (such as pain intensity and depressive and anxiety symptoms) in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. PMID:23805183

Dissociative Disorders: Between Neurosis and Psychosis

PubMed Central

Devillé, C.; Moeglin, C.; Sentissi, O.

2014-01-01

Dissociative disorders are a set of disorders defined by a disturbance affecting functions that are normally integrated with a prevalence of 2.4 percent in industrialised countries. These disorders are often poorly diagnosed or misdiagnosed because of sharing common clinical features with psychotic disorders, but requiring a very different trajectory of care. Repeated clinical situations in a crisis centre in Geneva provided us with a critical overview of current evidence of knowledge in clinical and etiopathological field about dissociative disorders. Because of their multiple expressions and the overlap with psychotic disorders, we focused on the clinical aspects using three different situations to better understand their specificity and to extend our thinking to the relevance of terms “neurosis” and “psychosis.” Finally, we hope that this work might help physicians and psychiatrists to become more aware of this complex set of disorders while making a diagnosis. PMID:25405051

[Diagnosis and clinical management of urinary tract infection].

PubMed

Heilberg, Ita Pfeferman; Schor, Nestor

2003-01-01

A review about recent aspects on diagnosis and clinical management of urinary tract infection (UTI) is presented. There is a wide variation in clinical presentation of UTI which include different forms as cystitis, pyelonephritis, urethral syndrome and the clinical relevance of asymptomatic bacteriuria and low-count bacteriuria that must be distinguished from contamination. Pathogenetic aspects concerning bacterial virulence as well as host factors in susceptibility to UTI as urinary tract obstruction, vesicoureteral reflux, indwelling bladder catheters, pregnancy, diabetes mellitus, sexual activity, contraceptive methods, prostatism, menopause, advanced age and renal transplantation are discussed. Diagnostic criteria and the most common tests utilized for differentiation between lower and upper UTI have been reviewed. The authors conclude that a careful evaluation of the underlying factors is required for the correct diagnosis of UTI and to prevent recurrence and that appropriate strategies and specific therapeutic regimens may maximize the benefit while reducing costs and adverse reactions.

Peritoneal dialysis glossary 2009.

PubMed

Liakopoulos, Vassilios; Stefanidis, Ioannis; Dombros, Nicholas V

2010-06-01

A number of attempts to create a commonly accepted terminology regarding definitions and terms used for clinical entities, methods, problems, and materials encountered by health professionals involved in peritoneal dialysis (PD) were undertaken in the past, the last one in 1990. Later on, some relevant sporadic attempts in a number of textbooks have been made, but they did not include the whole spectrum of PD. This glossary is an attempt to address the need for a universally accepted PD terminology including the latest advances in PD connection systems and fluids.

All for one and FOSL1 for all: FOSL1 at the crossroads of lung and pancreatic cancer driven by mutant KRAS.

PubMed

Vallejo, Adrian; Valencia, Karmele; Vicent, Silvestre

2017-01-01

KRAS proto-oncogene, GTPase ( KRAS ) remains refractory to current therapies. We devised an integrative cross-tumor approach to expose common core elements up-regulated in mutant KRAS cancers that could provide new treatment opportunities. This approach identified FOSL1 ( Fos-like antigen 1 ) as a clinically and functionally relevant gene in mutant KRAS -driven lung and pancreatic cancers, and unveiled downstream transcriptional targets amenable to pharmacological inhibition.

Teaching strategies for assessing and managing urinary incontinence in older adults.

PubMed

Bradway, Christine; Cacchione, Pamela

2010-07-01

Urinary incontinence is common and affects many aspects of older adults' lives; therefore, it is essential that nursing faculty include this content in classroom and clinical teaching situations. This article describes innovative strategies for teaching upper-level nursing students (e.g., junior and senior undergraduates) about urinary incontinence in older adults, specifically, the relevant anatomy and physiology of continence and associated pathophysiology of urinary incontinence, risk factors and consequences, definitions and types, and effective nursing assessment and management strategies. Copyright 2010, SLACK Incorporated.

Multimodality imaging of foreign bodies of the musculoskeletal system.

PubMed

Jarraya, Mohamed; Hayashi, Daichi; de Villiers, Richard V; Roemer, Frank W; Murakami, Akira M; Cossi, Alda; Guermazi, Ali

2014-07-01

The purpose of this article is to clarify the most relevant points in managing suspected foreign bodies of the musculoskeletal system on the basis of a literature review and published reports with cases to illustrate each type on different imaging modalities. Foreign bodies of the musculoskeletal system are a common problem in emergency departments, with more than a third missed in the initial clinical evaluation. These retained objects may result in various complications and also offer fertile ground for litigation.

Cardiac computed tomography of an asymptomatic 48-year-old woman with ALCAPA syndrome.

PubMed

Sajjadieh Khajouei, Amirreza; Samie-Nasab, Mohammadreza; Behjati, Mohaddeseh; Biederman, Robert W

2016-12-01

Untreated ALCAPA cases most often die in infancy. Adults with untreated ALCAPA commonly present with mitral regurgitation, severe left ventricular dysfunction, and sometimes myocardial infarction. Herein, we present an asymptomatic adult female with ALCAPA recognized through cardiac computed tomography (CT). In ALCAPA, like other coronary anomalies, cardiac CT is often instrumental in providing unique noninvasive and clinically relevant evaluation. Herein, we present an atypical presentation of an asymptomatic middle-aged adult female with ALCAPA. © 2016, Wiley Periodicals, Inc.

Non-pharmacological approaches to alleviate distress in dementia care.

PubMed

Mitchell, Gary; Agnelli, Joanne

2015-11-25

Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature.

Adrenomedullin and Pregnancy: Perspectives from Animal Models to Humans

PubMed Central

Lenhart, Patricia M.; Caron, Kathleen M.

2012-01-01

A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With more extensive mechanistic studies and improved consistency in clinical measurements of adrenomedullin, there is great potential for the development of adrenomedullin as a clinically-relevant biomarker in pregnancy and pregnancy complications. PMID:22425034

Improving Atrial Fibrillation Therapy: Is There a Gene for That?

PubMed Central

Hucker, William J.; Hanley, Alan; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we will summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. PMID:28427583

[Pheochromocytoma and paraganglioma in childhood: a report of 2 cases report].

PubMed

Mosquera Gorostidi, A; Justo Ranera, A; Zakirian Denis, S E; González Temprano, N; Sagaseta de Ilúrdoz Uranga, M; Molina Garicano, J

2015-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors in children and most of them are sporadic. However, they represent the most common endocrine tumor in childhood, and hereditary tumor syndromes are most relevant in these age. Advances in genetic, biochemistry and imaging techniques have revised the management of these tumors; thus A biochemical study should be always initiated once the clinical diagnosis is suspected, followed by imaging and molecular studies, particularly in the context of known familial disease. The diagnostic and therapeutic features are reviewed after the presentation of two clinical cases, where the second one is a patient with type 1 Neurofibromatosis. Copyright © 2014. Published by Elsevier Espana.

Scanning electron microscopy fractography analysis of fractured hollow implants.

PubMed

Sbordone, Ludovico; Traini, Tonino; Caputi, Sergio; Scarano, Antonio; Bortolaia, Claudia; Piattelli, Adriano

2010-01-01

Fracture of the implant is one of the possible complications affecting dental implants; it is a rare event but of great clinical relevance. The aim of the present study was to perform a scanning electron microscopy (SEM) fractography evaluation of 7 International Team for oral Implantology (ITI) hollow implants removed because of fracture. The most common clinical risk factors, such as malocclusion, bruxism, and cantilevers on the prosthesis, were absent. Seven fractured ITI hollow implants were retrieved from 5 patients and were analyzed with the use of SEM. SEM analysis showed typical signs of a cleavage-type fracture. Fractures could be due to an association of multiple factors such as fatigue, inner defects, material electrochemical problems, and tensocorrosion.

Collaborative derivation of reference intervals for major clinical laboratory tests in Japan.

PubMed

Ichihara, Kiyoshi; Yomamoto, Yoshikazu; Hotta, Taeko; Hosogaya, Shigemi; Miyachi, Hayato; Itoh, Yoshihisa; Ishibashi, Midori; Kang, Dongchon

2016-05-01

Three multicentre studies of reference intervals were conducted recently in Japan. The Committee on Common Reference Intervals of the Japan Society of Clinical Chemistry sought to establish common reference intervals for 40 laboratory tests which were measured in common in the three studies and regarded as well harmonized in Japan. The study protocols were comparable with recruitment mostly from hospital workers with body mass index ≤28 and no medications. Age and sex distributions were made equal to obtain a final data size of 6345 individuals. Between-subgroup differences were expressed as the SD ratio (between-subgroup SD divided by SD representing the reference interval). Between-study differences were all within acceptable levels, and thus the three datasets were merged. By adopting SD ratio ≥0.50 as a guide, sex-specific reference intervals were necessary for 12 assays. Age-specific reference intervals for females partitioned at age 45 were required for five analytes. The reference intervals derived by the parametric method resulted in appreciable narrowing of the ranges by applying the latent abnormal values exclusion method in 10 items which were closely associated with prevalent disorders among healthy individuals. Sex- and age-related profiles of reference values, derived from individuals with no abnormal results in major tests, showed peculiar patterns specific to each analyte. Common reference intervals for nationwide use were developed for 40 major tests, based on three multicentre studies by advanced statistical methods. Sex- and age-related profiles of reference values are of great relevance not only for interpreting test results, but for applying clinical decision limits specified in various clinical guidelines. © The Author(s) 2015.

How to Assess Gaming-Induced Benefits on Attention and Working Memory.

PubMed

Mishra, Jyoti; Bavelier, Daphne; Gazzaley, Adam

2012-06-01

Our daily actions are driven by our goals in the moment, constantly forcing us to choose among various options. Attention and working memory are key enablers of that process. Attention allows for selective processing of goal-relevant information and rejecting task-irrelevant information. Working memory functions to maintain goal-relevant information in memory for brief periods of time for subsequent recall and/or manipulation. Efficient attention and working memory thus support the best extraction and retention of environmental information for optimal task performance. Recent studies have evidenced that attention and working memory abilities can be enhanced by cognitive training games as well as entertainment videogames. Here we review key cognitive paradigms that have been used to evaluate the impact of game-based training on various aspects of attention and working memory. Common use of such methodology within the scientific community will enable direct comparison of the efficacy of different games across age groups and clinical populations. The availability of common assessment tools will ultimately facilitate development of the most effective forms of game-based training for cognitive rehabilitation and education.

How to Assess Gaming-Induced Benefits on Attention and Working Memory

PubMed Central

Mishra, Jyoti; Bavelier, Daphne

2012-01-01

Abstract Our daily actions are driven by our goals in the moment, constantly forcing us to choose among various options. Attention and working memory are key enablers of that process. Attention allows for selective processing of goal-relevant information and rejecting task-irrelevant information. Working memory functions to maintain goal-relevant information in memory for brief periods of time for subsequent recall and/or manipulation. Efficient attention and working memory thus support the best extraction and retention of environmental information for optimal task performance. Recent studies have evidenced that attention and working memory abilities can be enhanced by cognitive training games as well as entertainment videogames. Here we review key cognitive paradigms that have been used to evaluate the impact of game-based training on various aspects of attention and working memory. Common use of such methodology within the scientific community will enable direct comparison of the efficacy of different games across age groups and clinical populations. The availability of common assessment tools will ultimately facilitate development of the most effective forms of game-based training for cognitive rehabilitation and education. PMID:24761314

Vulnerability factors in OCD symptoms: cross-cultural comparisons between Turkish and Canadian samples.

PubMed

Yorulmaz, Orçun; Gençöz, Tülin; Woody, Sheila

2010-01-01

Recent findings have suggested some potential psychological vulnerability factors for development of obsessive-compulsive (OC) symptoms, including cognitive factors of appraisal and thought control, religiosity, self-esteem and personality characteristics such as neuroticism. Studies demonstrating these associations usually come from Western cultures, but there may be cultural differences relevant to these vulnerability factors and OC symptoms. The present study examined the relationship between putative vulnerability factors and OC symptoms by comparing non-clinical samples from Turkey and Canada, two countries with quite different cultural characteristics. The findings revealed some common correlates such as neuroticism and certain types of metacognition, including appraisals of responsibility/threat estimation and perfectionism/need for certainty, as well as thought-action fusion. However, culture-specific factors were also indicated in the type of thought control participants used. For OC disorder symptoms, Turkish participants were more likely to utilize worry and thought suppression, while Canadian participants tended to use self-punishment more frequently. The association with common factors supports the cross-cultural validity of some factors, whereas unique factors suggest cultural features that may be operative in cognitive processes relevant to OC symptoms.

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

2018-02-01

Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders. Published by Elsevier Inc.

Differential diagnosis of apneas in preterm infants.

PubMed

Paul, Karel; Melichar, Jan; Miletín, Jan; Dittrichová, Jaroslava

2009-02-01

Clinically relevant apneas, which are common in preterm infants, may adversely affect later neuropsychological condition in this group of patients. Pharmacotherapy to stimulate respiratory functions may be unsuccessful. Polygraphic recording may help in the differential diagnosis of these clinically relevant events. Twenty-nine preterm neonates born before 36 weeks of gestational age were examined using polygraphic recording (respiration--two channels, perioral electromyography, oxygen saturation, heart rate, electroencephalography, electrocardiography, electrooculography). The examination was ordered by the attending physician after an unsuccessful treatment of apnea by Aminophylline, and it should contribute to the clarification of the causes of these events. In the course of the polygraphic examinations, altogether 63 episodes were recorded during which the pulse oximeter alarm signal was set off. In 42 cases, the alarm signal was set off in events during which SaO(2) fell below 85%. In the remaining 21 cases, the alarm signal was set off in episodes during which early bradycardia below 90/min occurred. The onset of apnea was very often associated with the phasic increase of the perioral electromyography and with electroencephalography arousal reaction. Because of suspicion that these apneas may be triggered by episodes of gastroesophageal reflux, the interruption of the Aminophylline treatment and setting up an antireflux regimen were recommended. These therapeutic measures had a positive effect: The frequency of alarm signals decreased within 48 h by a statistically significant 50%. In cases where the pharmacotherapy of apnea by stimulation of respiratory functions is not successful, differential diagnostic analysis should be performed. Polygraphy may contribute to the clarification of the causes underlying clinically relevant apneas in a view of newly described polygraphic signs. It is feasible to suspect, based on these signs, that gastroesophageal reflux is the cause for clinically significant apneas in that case.

Evidence in clinical reasoning: a computational linguistics analysis of 789,712 medical case summaries 1983-2012.

PubMed

Seidel, Bastian M; Campbell, Steven; Bell, Erica

2015-03-21

Better understanding of clinical reasoning could reduce diagnostic error linked to 8% of adverse medical events and 30% of malpractice cases. To a greater extent than the evidence-based movement, the clinical reasoning literature asserts the importance of practitioner intuition—unconscious elements of diagnostic reasoning. The study aimed to analyse the content of case report summaries in ways that explored the importance of an evidence concept, not only in relation to research literature but also intuition. The study sample comprised all 789,712 abstracts in English for case reports contained in the database PUBMED for the period 1 January 1983 to 31 December 2012. It was hypothesised that, if evidence and intuition concepts were viewed by these clinical authors as essential to understanding their case reports, they would be more likely to be found in the abstracts. Computational linguistics software was used in 1) concept mapping of 21,631,481 instances of 201 concepts, and 2) specific concept analyses examining 200 paired co-occurrences for 'evidence' and research 'literature' concepts. 'Evidence' is a fundamentally patient-centred, intuitive concept linked to less common concepts about underlying processes, suspected disease mechanisms and diagnostic hunches. In contrast, the use of research literature in clinical reasoning is linked to more common reasoning concepts about specific knowledge and descriptions or presenting features of cases. 'Literature' is by far the most dominant concept, increasing in relevance since 2003, with an overall relevance of 13% versus 5% for 'evidence' which has remained static. The fact that the least present types of reasoning concepts relate to diagnostic hunches to do with underlying processes, such as what is suspected, raises questions about whether intuitive practitioner evidence-making, found in a constellation of dynamic, process concepts, has become less important. The study adds support to the existing corpus of research on clinical reasoning, by suggesting that intuition involves a complex constellation of concepts important to how the construct of evidence is understood. The list of concepts the study generated offers a basis for reflection on the nature of evidence in diagnostic reasoning and the importance of intuition to that reasoning.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

PubMed

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA , NF1 , CDKN2A , or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics. © AlphaMed Press 2017.

Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature.

PubMed

Henderson, Jette; Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

2018-05-04

Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET's phenotype representation with PheKnow-Cloud's by using PheKnow-Cloud's experimental setup. In PIVET's framework, we also introduce a statistical model trained on domain expert-verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but PIVET's analysis is an order of magnitude faster than that of PheKnow-Cloud. Not only is PIVET much faster, it can be scaled to a larger corpus and still retain speed. We evaluated multiple classification models on top of the PIVET framework and found ridge regression to perform best, realizing an average F1 score of 0.91 when predicting clinically relevant phenotypes. Our study shows that PIVET improves on the most notable existing computational tool for phenotype validation in terms of speed and automation and is comparable in terms of accuracy. ©Jette Henderson, Junyuan Ke, Joyce C Ho, Joydeep Ghosh, Byron C Wallace. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.05.2018.

Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature

PubMed Central

Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

2018-01-01

Background Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. Objective The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. Methods PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET’s phenotype representation with PheKnow-Cloud’s by using PheKnow-Cloud’s experimental setup. In PIVET’s framework, we also introduce a statistical model trained on domain expert–verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. Results PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but PIVET’s analysis is an order of magnitude faster than that of PheKnow-Cloud. Not only is PIVET much faster, it can be scaled to a larger corpus and still retain speed. We evaluated multiple classification models on top of the PIVET framework and found ridge regression to perform best, realizing an average F1 score of 0.91 when predicting clinically relevant phenotypes. Conclusions Our study shows that PIVET improves on the most notable existing computational tool for phenotype validation in terms of speed and automation and is comparable in terms of accuracy. PMID:29728351

PM101: intravenous amiodarone formulation changes can improve medication safety.

PubMed

Souney, Paul F; Cooper, Warren D; Cushing, Daniel J

2010-03-01

Intravenous amiodarone (A-IV) is used to manage ventricular and atrial arrhythmias. The current formulation uses polysorbate 80 and benzyl alcohol to maintain amiodarone in solution, and these co-solvents are linked with clinically-important adverse events and pharmaceutical incompatibilities. PM101 is a recently FDA-approved intravenous formulation of amiodarone that uses a cyclodextrin to solubilize amiodarone. This review describes the clinical and pharmaceutical development of formulations of amiodarone for intravenous administration. The medical and pharmaceutical literature was searched for papers discussing A-IV, PM101 and their formulation components. Relevant literature was identified starting from 1948 to the present. The reader will learn about the important medical and pharmaceutical issues complicating A-IV administration, including an understanding of related hypotension and compatibility with commonly used infusion materials and how these issues may impact drug safety. PM101 has been developed to address several of these important issues. PM101 is a new formulation of A-IV that is stable in commonly used infusion materials and avoids co-solvent related toxicities.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Starobova, Hana; Vetter, Irina

2017-01-01

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280

Immune-mediated diseases: what can be found in the oral cavity?

PubMed

Bascones-Martínez, Antonio; García-García, Virginia; Meurman, Jukka H; Requena-Caballero, Luis

2015-03-01

Immune-mediated diseases frequently affect oral mucosa, which may often be the first site of clinical manifestation. In this review, we describe the most important oral lesions related to inflammatory disorders and present their management and novel therapies. The review is based on an open PubMed literature search from 1980 to 2012 with relevant keywords. Pemphigus vulgaris, oral lichen planus, cicatricial pemphigoid, erythema multiforme, Stevens-Johnson syndrome, systemic lupus erythematosus, Sjögren's syndrome, and linear IgA dermatosis are the immune-mediated diseases with oral manifestations discussed. Etiology is unknown in most of these diseases, but recently some of them have been found to share common genes. Modern treatment of these diseases is based on drugs that interfere along the pathogenic mechanisms instead of the still commonly used palliative measures. However, the immunomodulatory drugs may also cause oral side effects, complicating the clinical picture. Therefore, consulting dental or oral medicine specialists can be necessary in some cases with various immune-mediated diseases. © 2014 The International Society of Dermatology.

Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

PubMed

Spillane, J; Kullmann, D M; Hanna, M G

2016-01-01

Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. 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/

Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

PubMed

Manning, H Charles; Buck, Jason R; Cook, Rebecca S

2016-02-01

Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The current deconstruction of paradoxes: one sign of the ongoing methodological "revolution".

PubMed

Porta, Miquel; Vineis, Paolo; Bolúmar, Francisco

2015-10-01

The current deconstruction of paradoxes is one among several signs that a profound renewal of methods for clinical and epidemiological research is taking place; perhaps for some basic life sciences as well. The new methodological approaches have already deconstructed and explained long puzzling apparent paradoxes, including the (non-existent) benefits of obesity in diabetics, or of smoking in low birth weight. Achievements of the new methods also comprise the elucidation of the causal structure of long-disputed and highly complex questions, as Berkson's bias and Simpson's paradox, and clarifying reasons for deep controversies, as those on estrogens and endometrial cancer, or on adverse effects of hormone replacement therapy. These are signs that the new methods can go deeper and beyond the methods in current use. A major example of a highly relevant idea is: when we condition on a common effect of a pair of variables, then a spurious association between such pair is likely. The implications of these ideas are potentially vast. A substantial number of apparent paradoxes may simply be the result of collider biases, a source of selection bias that is common not just in epidemiologic research, but in many types of research in the health, life, and social sciences. The new approaches develop a new framework of concepts and methods, as collider, instrumental variables, d-separation, backdoor path and, notably, Directed Acyclic Graphs (DAGs). The current theoretical and methodological renewal-or, perhaps, "revolution"-may be changing deeply how clinical and epidemiological research is conceived and performed, how we assess the validity and relevance of findings, and how causal inferences are made. Clinical and basic researchers, among others, should get acquainted with DAGs and related concepts.

Mind-body medicine: state of the science, implications for practice.

PubMed

Astin, John A; Shapiro, Shauna L; Eisenberg, David M; Forys, Kelly L

2003-01-01

Although emerging evidence during the past several decades suggests that psychosocial factors can directly influence both physiologic function and health outcomes, medicine had failed to move beyond the biomedical model, in part because of lack of exposure to the evidence base supporting the biopsychosocial model. The literature was reviewed to examine the efficacy of representative psychosocial-mind-body interventions, including relaxation, (cognitive) behavioral therapies, meditation, imagery, biofeedback, and hypnosis for several common clinical conditions. An electronic search was undertaken of the MEDLINE, PsycLIT, and the Cochrane Library databases and a manual search of the reference sections of relevant articles for related clinical trials and reviews of the literature. Studies examining mind-body interventions for psychological disorders were excluded. Owing to space limitations, studies examining more body-based therapies, such as yoga and tai chi chuan, were also not included. Data were extracted from relevant systematic reviews, meta-analyses, and randomized controlled trials. Drawing principally from systematic reviews and meta-analyses, there is considerable evidence of efficacy for several mind-body therapies in the treatment of coronary artery disease (eg, cardiac rehabilitation), headaches, insomnia, incontinence, chronic low back pain, disease and treatment-related symptoms of cancer, and improving postsurgical outcomes. We found moderate evidence of efficacy for mind-body therapies in the areas of hypertension and arthritis. Additional research is required to clarify the relative efficacy of different mind-body therapies, factors (such as specific patient characteristics) that might predict more or less successful outcomes, and mechanisms of action. Research is also necessary to examine the cost offsets associated with mind-body therapies. There is now considerable evidence that an array of mind-body therapies can be used as effective adjuncts to conventional medical treatment for a number of common clinical conditions.

Gamma-delta t-cell lymphomas.

PubMed

Foppoli, Marco; Ferreri, Andrés J M

2015-03-01

Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, which naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kinetic modeling in PET imaging of hypoxia

PubMed Central

Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

2014-01-01

Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

PubMed

Germain, M A; Hatton, A; Williams, S; Matthews, J B; Stone, M H; Fisher, J; Ingham, E

2003-02-01

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Factitious disorders and malingering in relation to functional neurologic disorders.

PubMed

Bass, C; Halligan, P

2016-01-01

Interest in malingering has grown in recent years, and is reflected in the exponential increase in academic publications since 1990. Although malingering is more commonly detected in medicolegal practice, it is not an all-or-nothing presentation and moreover can vary in the extent of presentation. As a nonmedical disorder, the challenge for clinical practice remains that malingering by definition is intentional and deliberate. As such, clinical skills alone are often insufficient to detect it and we describe psychometric tests such as symptom validity tests and relevant nonmedical investigations. Finally, we describe those areas of neurologic practice where symptom exaggeration and deception are more likely to occur, e.g., postconcussional syndrome, psychogenic nonepileptic seizures, motor weakness and movement disorders, and chronic pain. Factitious disorders are rare in clinical practice and their detection depends largely on the level of clinical suspicion supported by the systematic collection of relevant information from a variety of sources. In this chapter we challenge the accepted DSM-5 definition of factitious disorder and suggest that the traditional glossaries have neglected the extent to which a person's reported symptoms can be considered a product of intentional choice or selective psychopathology largely beyond the subject's voluntary control, or more likely, both. We present evidence to suggest that neurologists preferentially diagnose factitious presentations in healthcare workers as "hysterical," possibly to avoid the stigma of simulated illness. © 2016 Elsevier B.V. All rights reserved.

A review on Pharmacological and clinical aspects of Linum usitatissimum L.

PubMed

Ansari, Ramin; Zarshenas, Mohammad Mehdi; Dadbakhsh, Amir Hossein

2018-05-20

Linum usitatissimum L., known as common Flax or linseed, from the family Linnaceae, has long been cultivated in different nations due to its applications in medicine and industry. The present study aims to collect nearly all available information about chemical constituents of Flax, as well as pharmacological properties and confirmed clinical usages of it. We searched through databases such as Scopus and PubMed for relevant literatures using the keywords: (Linum usitatissimum), (pharmacology) and (phytochemical) from the beginning to 13 Aug 2017. Nearly 60 relevant papers, relating to pharmacological and phytochemical constituent of L. usitatissimum were selected. According to our researches, various properties were attributed to L. usitatisimum including: antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, Antiprotozoal, insecticidal, Analgesic, anti-hyperlipidemia, Anti-hyperglycemic, Anti-tumor, wound healing and Feticidal activities. There were also many reports to the disease preventive and healing properties of the flax. Diseases like: GI disorders, cardiovascular, urogenital, respiratory diseases and some neurological syndromes were mentioned to be treated by Flax. The application of Flax in drug formulations was also investigated. Despite so much animal studies that have been accomplished, there haven't been enough clinical trials done on pharmacological properties of L. usitatissimum. Therefore this study could be considered as a concise and up to date overview for further facile studies and clinical trials over the valuable plant, L. usitatissimum. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Skin marker placement by technologist prior to knee MRI helps identify clinically relevant pathologies.

PubMed

Wadhwa, Vibhor; Weissman, Eric; Hayashi, Daichi; Xi, Yin; Chhabra, Avneesh

2017-12-15

Majority of musculoskeletal cross-sectional imaging requests have a non-revealing and non-specific clinical history of pain. However, the location of pain is very relevant towards arriving at a specific orthopedic diagnosis. The purpose of this research was to study the impact of skin marker placement and training of technologists prior to knee MRI in detection of clinically important findings. Total 200 consecutive left knee MRIs were evaluated before and after technologist training with regards to marker placement at the site of clinical symptoms or palpable finding. Marker location in relation to the knee was recorded and important findings were classified as correlated important finding, non-correlated important finding, other compartment important finding in non-correlated cases, and diffuse abnormality, i.e. tri-compartmental cartilage defects in both correlated and non-correlated cases. Differences among scans before and after technologist training were analyzed. The marker placement was observed in higher proportion of patients in post-training scans (78% vs 60%, p = 0.00). The most common location of the marker was in anterior or anterolateral knee (32% and 34% cases, respectively). The marker-important finding correlation was also higher post training, but not statistically significant (53% versus 38%, p = 0.57). Important findings correlated with the marker in more than 50% of the scans in the post-training set. Marker placement can aid in detection of clinically important imaging finding and technologist training aids in increased rates of marker placement and improved correlation.

Application of a diagnosis-based clinical decision guide in patients with low back pain.

PubMed

Murphy, Donald R; Hurwitz, Eric L

2011-10-21

Low back pain (LBP) is common and costly. Development of accurate and efficacious methods of diagnosis and treatment has been identified as a research priority. A diagnosis-based clinical decision guide (DBCDG; previously referred to as a diagnosis-based clinical decision rule) has been proposed which attempts to provide the clinician with a systematic, evidence-based means to apply the biopsychosocial model of care. The approach is based on three questions of diagnosis. The purpose of this study is to present the prevalence of findings using the DBCDG in consecutive patients with LBP. Demographic, diagnostic and baseline outcome measure data were gathered on a cohort of LBP patients examined by one of three examiners trained in the application of the DBCDG. Data were gathered on 264 patients. Signs of visceral disease or potentially serious illness were found in 2.7%. Centralization signs were found in 41%, lumbar and sacroiliac segmental signs in 23% and 27%, respectively and radicular signs were found in 24%. Clinically relevant myofascial signs were diagnosed in 10%. Dynamic instability was diagnosed in 63%, fear beliefs in 40%, central pain hypersensitivity in 5%, passive coping in 3% and depression in 3%. The DBCDG can be applied in a busy private practice environment. Further studies are needed to investigate clinically relevant means to identify central pain hypersensitivity, poor coping and depression, correlations and patterns among the diagnostic components of the DBCDG as well as inter-examiner reliability and efficacy of treatment based on the DBCDG.

Urinary tract infections during pregnancy.

PubMed

Le, Jennifer; Briggs, Gerald G; McKeown, Anna; Bustillo, Gerardo

2004-10-01

To provide a comprehensive review of urinary tract infections (UTIs) during pregnancy. All aspects of UTIs, including epidemiology, pathogenesis, resistance, clinical features, diagnosis, treatment, and prevention, were reviewed. MEDLINE (1966-August 2003) and Cochrane Library searches were performed using the key search terms urinary tract infection, pyelonephritis, cystitis, asymptomatic bacteriuria, and resistance. All article abstracts were evaluated for relevance. Only articles pertaining to pregnancy were included. The majority of published literature were review articles; the number of original clinical studies was limited. UTIs are the most common bacterial infections during pregnancy. They are characterized by the presence of significant bacteria anywhere along the urinary tract. Pyelonephritis is the most common severe bacterial infection that can lead to perinatal and maternal complications including premature delivery, infants with low birth weight, fetal mortality, preeclampsia, pregnancy-induced hypertension, anemia, thrombocytopenia, and transient renal insufficiency. Enterobacteriaceae account for 90% of UTIs. The common antibiotics used are nitrofurantoin, cefazolin, cephalexin, ceftriaxone, and gentamicin. Therapeutic management of UTIs in pregnancy requires proper diagnostic workup and thorough understanding of antimicrobial agents to optimize maternal outcome, ensure safety to the fetus, and prevent complications that lead to significant morbidity and mortality in both the fetus and the mother.

Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?

PubMed

Romo, Matthew L; Carpio, Arturo; Kelvin, Elizabeth A

2014-04-01

Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized. © 2014, The American College of Clinical Pharmacology.

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.

Development problems were common five years after positive screening for language disorders and, or, autism at 2.5 years of age.

PubMed

Miniscalco, Carmela; Fernell, Elisabeth; Thompson, Lucy; Sandberg, Eva; Kadesjö, Björn; Gillberg, Christopher

2018-04-10

This study identified whether children who had screened positive for either developmental language disorder (DLD) or autism spectrum disorder (ASD) at the age of 2.5 years had neurodevelopmental assessments five years later. Our study cohort were 288 children born from 1 July 2008 to 20 June 2009 who screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were referred to, and assessed, at the Paediatric Speech and Language Pathology clinic (n = 176) or the Child Neuropsychiatry Clinic (n = 61) at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Clinical registers covering all relevant outpatient clinics were reviewed five years later with regard to established diagnoses. When the 237 were followed up five years later, 96 (40%) had established neurodevelopmental disorders or problems, often beyond DLD and ASD. Co-existing problems were common in this cohort and multidisciplinary assessments were indicated. The other 60% did not appear in subsequent clinic records. It is likely that this 40% was a minimum rate and that more children will be referred for developmental problems later. Five years after they had been screened positive for DLD and, or autism at 2.5 years, 40% of our cohort had remaining or other developmental problems. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Causality or Relatedness Assessment in Adverse Drug Reaction and Its Relevance in Dermatology.

PubMed

Pande, Sushil

2018-01-01

Causality assessment essentially means finding a causal association or relationship between a drug and drug reaction. Identifying the culprit drug or drugs can be lifesaving or helpful in preventing the further damage caused by the drug to our body systems. In dermatology practice, when it comes to cutaneous adverse drug reaction, this is much more important and relevant because many aetiologies can produce a similar cutaneous manifestation. There are multiple criteria or algorithms available as of now for establishing a causal relationship in cases of adverse drug reaction (ADR), indicating that none of them is specific or complete. Most of these causality assessment tools (CATs) use four cardinal principles of diagnosis of ADR such as temporal relationship of drug with the drug reaction, biological plausibility of the drug causing a reaction, dechallenge, and rechallenge. The present study reviews some of the established or commonly used CATs and its implications or relevance to dermatology in clinical practice.

An optimised protocol for isolation of RNA from small sections of laser-capture microdissected FFPE tissue amenable for next-generation sequencing.

PubMed

Amini, Parisa; Ettlin, Julia; Opitz, Lennart; Clementi, Elena; Malbon, Alexandra; Markkanen, Enni

2017-08-23

Formalin-fixed paraffin embedded (FFPE) tissue constitutes a vast treasury of samples for biomedical research. Thus far however, extraction of RNA from FFPE tissue has proved challenging due to chemical RNA-protein crosslinking and RNA fragmentation, both of which heavily impact on RNA quantity and quality for downstream analysis. With very small sample sizes, e.g. when performing Laser-capture microdissection (LCM) to isolate specific subpopulations of cells, recovery of sufficient RNA for analysis with reverse-transcription quantitative PCR (RT-qPCR) or next-generation sequencing (NGS) becomes very cumbersome and difficult. We excised matched cancer-associated stroma (CAS) and normal stroma from clinical specimen of FFPE canine mammary tumours using LCM, and compared the commonly used protease-based RNA isolation procedure with an adapted novel technique that additionally incorporates a focused ultrasonication step. We successfully adapted a protocol that uses focused ultrasonication to isolate RNA from small amounts of deparaffinised, stained, clinical LCM samples. Using this approach, we found that total RNA yields could be increased by 8- to 12-fold compared to a commonly used protease-based extraction technique. Surprisingly, RNA extracted using this new approach was qualitatively at least equal if not superior compared to the old approach, as Cq values in RT-qPCR were on average 2.3-fold lower using the new method. Finally, we demonstrate that RNA extracted using the new method performs comparably in NGS as well. We present a successful isolation protocol for extraction of RNA from difficult and limiting FFPE tissue samples that enables successful analysis of small sections of clinically relevant specimen. The possibility to study gene expression signatures in specific small sections of archival FFPE tissue, which often entail large amounts of highly relevant clinical follow-up data, unlocks a new dimension of hitherto difficult-to-analyse samples which now become amenable for investigation.

Boomerang sign on MRI.

PubMed

Hirsch, Karen G; Hoesch, Robert E

2012-06-01

Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients. Case report with relevant image and review of the literature. Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology. Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

Nutrition and skin.

PubMed

Pappas, Apostolos; Liakou, Aikaterini; Zouboulis, Christos C

2016-09-01

Nutrition has long been associated with skin health, including all of its possible aspects from beauty to its integrity and even the aging process. Multiple pathways within skin biology are associated with the onset and clinical course of various common skin diseases, such as acne, atopic dermatitis, aging, or even photoprotection. These conditions have been shown to be critically affected by nutritional patterns and dietary interventions where well-documented studies have demonstrated beneficial effects of essential nutrients on impaired skin structural and functional integrity and have restored skin appearance and health. Although the subject could be vast, the intention of this review is to provide the most relevant and the most well-documented information on the role of nutrition in common skin conditions and its impact on skin biology.

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study

PubMed Central

Cross, G.; Taylor, D. R.; Sherwood, R. A.; Watson, P. J.

2016-01-01

Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further. PMID:27110372

Research methods to change clinical practice for patients with rare cancers.

PubMed

Billingham, Lucinda; Malottki, Kinga; Steven, Neil

2016-02-01

Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Qualitative analysis of healthcare professionals' viewpoints on the role of ethics committees and hospitals in the resolution of clinical ethical dilemmas.

PubMed

Marcus, Brian S; Shank, Gary; Carlson, Jestin N; Venkat, Arvind

2015-03-01

Ethics consultation is a commonly applied mechanism to address clinical ethical dilemmas. However, there is little information on the viewpoints of health care providers towards the relevance of ethics committees and appropriate application of ethics consultation in clinical practice. We sought to use qualitative methodology to evaluate free-text responses to a case-based survey to identify thematically the views of health care professionals towards the role of ethics committees in resolving clinical ethical dilemmas. Using an iterative and reflexive model we identified themes that health care providers support a role for ethics committees and hospitals in resolving clinical ethical dilemmas, that the role should be one of mediation, rather than prescription, but that ultimately legal exposure was dispositive compared to ethical theory. The identified theme of legal fears suggests that the mediation role of ethics committees is viewed by health care professionals primarily as a practical means to avoid more worrisome medico-legal conflict.

Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement : Diabetes mellitus and thyroid disorders: recommendations for clinical practice.

PubMed

Guastamacchia, Edoardo; Triggiani, Vincenzo; Aglialoro, Alberto; Aiello, Antimo; Ianni, Lucia; Maccario, Mauro; Zini, Michele; Giorda, Carlo; Guglielmi, Rinaldo; Betterle, Corrado; Attanasio, Roberto; Borretta, Giorgio; Garofalo, Piernicola; Papini, Enrico; Castello, Roberto; Ceriello, Antonio

2015-06-01

Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management.

Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study.

PubMed

Kent, A C C; Cross, G; Taylor, D R; Sherwood, R A; Watson, P J

2016-01-01

Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report.

PubMed

Carpenter, Paul A; Kitko, Carrie L; Elad, Sharon; Flowers, Mary E D; Gea-Banacloche, Juan C; Halter, Jörg P; Hoodin, Flora; Johnston, Laura; Lawitschka, Anita; McDonald, George B; Opipari, Anthony W; Savani, Bipin N; Schultz, Kirk R; Smith, Sean R; Syrjala, Karen L; Treister, Nathaniel; Vogelsang, Georgia B; Williams, Kirsten M; Pavletic, Steven Z; Martin, Paul J; Lee, Stephanie J; Couriel, Daniel R

2015-07-01

The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

What is the true clinical relevance of Simkania negevensis and other emerging Chlamydiales members?

PubMed

Vouga, M; Kebbi-Beghdadi, C; Liénard, J; Baskin, L; Baud, D; Greub, G

2018-05-01

Waddlia   chondrophila and Simkania negevensis are emerging Chlamydia- related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis -specific quantitative real-time PCR (qPCR) and a pan- Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila. We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (<1%) of exposure to S. negevensis. Conversely, humans were commonly exposed to W. chondrophila, with seroprevalences ranging from 8.6% to 32.5%. S. negevensis is not a clinically relevant pathogen, but further research investigating the role of W. chondrophila is needed.

Isolation, speciation, and antibiogram of clinically relevant non-diphtherial Corynebacteria (Diphtheroids).

PubMed

Reddy, B S; Chaudhury, A; Kalawat, U; Jayaprada, R; Reddy, Gsk; Ramana, B V

2012-01-01

Coryneform or the non-diphtherial Corynebacterium species largely remains a neglected group with the traditional consideration of these organisms as contaminants. This concept, however, is slowly changing in the light of recent observations. This study has been done to find out the species distribution and antibiogram of various members of the clinically relevant Coryneform group, isolated from various clinical materials. One hundred and fourteen non-duplicate isolates of diphtheroids from various clinical isolates were selected for the study. The isolates were identified to the species level by using a battery of tests; and antimicrobial susceptibility was tested by using a combination of Clinical and Laboratory Standards Institute (CLSI) and the British Society for Antimicrobial Chemotherapy (BSAC) guidelines, in the absence of definitive CLSI guidelines. Corynebacterium amycolatum was the predominant species (35.9%) in our series followed by the CDC Group G organisms (15.7%). Each of the remaining 19 species comprised of less than 10% of the isolates. More than half the total isolates were resistant to the penicillins, erythromycin, and clindamycin; while excellent activity (all the strains being susceptible) was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol and tetracycline also had good activity in inhibiting more than 80% of the isolates. Multiply drug resistance was exhibited by all the species. This study was an attempt to establish the clinical significance of coryneform organisms. The high level of resistance shown by this group to some of the common antibacterial agents highlights the importance of processing these isolates in select conditions to guide the clinicians towards an appropriate therapy.

Accurate and robust genomic prediction of celiac disease using statistical learning.

PubMed

Abraham, Gad; Tye-Din, Jason A; Bhalala, Oneil G; Kowalczyk, Adam; Zobel, Justin; Inouye, Michael

2014-02-01

Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87-0.89) and in independent replication across cohorts (AUC of 0.86-0.9), despite differences in ethnicity. The models explained 30-35% of disease variance and up to ∼43% of heritability. The GRS's utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE.

PubMed

Rao, Archana N; Grainger, David W

2014-04-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA's persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

PubMed Central

Rao, Archana N.; Grainger, David W.

2014-01-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA’s persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools. PMID:24765522

Development and classification of a robust inventory of near real-time outcome measurements for assessing information technology interventions in health care.

PubMed

Colicchio, Tiago K; Del Fiol, Guilherme; Scammon, Debra L; Bowes, Watson A; Facelli, Julio C; Narus, Scott P

2017-09-01

To develop and classify an inventory of near real-time outcome measures for assessing information technology (IT) interventions in health care and assess their relevance as perceived by experts in the field. To verify the robustness and coverage of a previously published inventory of measures and taxonomy, we conducted semi-structured interviews with clinical and administrative leaders from a large care delivery system to collect suggestions of outcome measures that can be calculated with data available in electronic format for near real-time monitoring of EHR implementations. We combined these measures with the most commonly reported in the literature. We then conducted two online surveys with subject-matter experts to collect their perceptions of the relevance of the measures, and identify other potentially relevant measures. With input from experienced health care leaders and informaticists, we developed an inventory of 102 outcome measures. These measures were classified into a taxonomy of commonly used measures around the categories of quality, productivity, and safety. Safety measures were rated as most relevant by subject-matter experts, especially those measuring medication processes. Clinician satisfaction and measures assessing mean time to complete tasks and time spent on electronic documentation were also rated as highly relevant. By expanding the coverage of our previously published inventory and taxonomy, we expect to help providers, health IT vendors and researchers to more effectively and consistently monitor the impact of EHR implementations in near real-time, and report more standardized outcomes in future studies. We identified several measures not commonly assessed by previous studies of IT implementations, especially those of safety and productivity, which deserve more attention from the broader informatics community. Our inventory of measures and taxonomy will help researchers identify gaps in their measurement approaches and report more standardized measurements of IT interventions that could be shared among researchers, hopefully facilitating comparison across future studies and increasing our understanding of the impact of IT interventions in health care. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-neglect: adaptation of a clinical tool to the practice of the medical examiner.

PubMed

Sauvageau, Anny; Hunter, Brian C

2012-09-01

Self-neglect is the inability or unwillingness to provide for oneself the goods and services needed to live safely and independently. It is the most common allegation reported to Adult Protective Services agencies throughout the United States. Unfortunately, it seems that most medical examiners and their teams are not trained appropriately on self-neglect and forget to ask pertinent questions and document relevant observations. The most important aspect of self-neglect for the medical examiner is to recognize the diagnosis to avoid confusion with other forms of elder abuse, particularly neglect from a third party. In this context, a self-neglect scale could be a useful tool to assist the death investigation team. In the clinical field, a self-neglect severity scale was developed by the Consortium for Research in Elder Self-Neglect of Texas. It is here proposed that a self-neglect severity scale for medical examiners should be developed, to assist the investigative team in assessing these common cases. This scale is developed by modifying the clinical scale to adapt it to the particular needs of death investigation. This scale can help the medical examiner and his team in approaching these deaths in a systematic and comprehensive way.

Comparison of Three Commercial Systems for Identification of Yeasts Commonly Isolated in the Clinical Microbiology Laboratory

PubMed Central

Wadlin, Jill K.; Hanko, Gayle; Stewart, Rebecca; Pape, John; Nachamkin, Irving

1999-01-01

We evaluated three commercial systems (RapID Yeast Plus System; Innovative Diagnostic Systems, Norcross, Ga.; API 20C Aux; bioMerieux-Vitek, Hazelwood, Mo.; and Vitek Yeast Biochemical Card, bioMerieux-Vitek) against an auxinographic and microscopic morphologic reference method for the ability to identify yeasts commonly isolated in our clinical microbiology laboratory. Two-hundred one yeast isolates were compared in the study. The RapID Yeast Plus System was significantly better than either API 20C Aux (193 versus 167 correct identifications; P < 0.0001) or the Vitek Yeast Biochemical Card (193 versus 173 correct identifications; P = 0.003) for obtaining correct identifications to the species level without additional testing. There was no significant difference between results obtained with API 20C Aux and the Vitek Yeast Biochemical Card system (P = 0.39). The API 20C Aux system did not correctly identify any of the Candida krusei isolates (n = 23) without supplemental testing and accounted for the major differences between the API 20C Aux and RapID Yeast Plus systems. Overall, the RapID Yeast Plus System was easy to use and is a good system for the routine identification of clinically relevant yeasts. PMID:10325356

Medical students' views about an undergraduate curriculum in psychiatry before and after clinical placements

PubMed Central

Oakley, Clare; Oyebode, Femi

2008-01-01

Background It has been suggested that medical students wish to focus their learning in psychiatry on general skills that are applicable to all doctors. This study seeks to establish what aspects of psychiatry students perceive to be relevant to their future careers and what psychiatric knowledge and skills they consider to be important. It is relevant to consider whether these expectations about learning needs vary prior to and post-placement in psychiatry. To what extent these opinions should influence curriculum development needs to be assessed. Methods A questionnaire was distributed to medical students before they commenced their psychiatry placement and after they had completed it. The questionnaire considered the relevance of psychiatry to their future careers, the relevance of particular knowledge and skills, the utility of knowledge of psychiatric specialties and the utility of different settings for learning psychiatry. Results The students felt skills relevant to all doctors, such as assessment of suicide risk, were more important than more specialist psychiatric skills, such as the management of schizophrenia. They felt that knowledge of how psychiatric illnesses present in general practice was important and it was a useful setting in which to learn psychiatry. They thought that conditions that are commonly seen in the general hospital are important and that liaison psychiatry was useful. Conclusion Two ways that medical students believe their teaching can be made more relevant to their future careers are highlighted in this study. Firstly, there is a need to focus on scenarios which students will commonly encounter in their initial years of employment. Secondly, psychiatry should be better integrated into the overall curriculum, with the opportunity for teaching in different settings. However, when developing curricula the need to listen to what students believe they should learn needs to be balanced against the necessity of teaching the fundamentals and principles of a speciality. PMID:18439278

Pediatric Allergic Contact Dermatitis: Clinical and Epidemiological Study in a Tertiary Hospital.

PubMed

Ortiz Salvador, J M; Esteve Martínez, A; Subiabre Ferrer, D; Victoria Martínez, A M; de la Cuadra Oyanguren, J; Zaragoza Ninet, V

Few epidemiological studies have investigated the incidence of allergic contact dermatitis in children. Underdiagnosis has been observed in some studies, with many cases in which the condition is not suspected clinically and patch tests are not performed. However, the prevalence of pediatric sensitization to allergens has been reported to be as high as 20%, and the diagnosis should therefore be contemplated as a possibility in this age group. We performed a retrospective analysis of the skin allergy database of the Dermatology Department of Consorcio Hospital General Universitario de Valencia. Children between 0 and 16 years of age diagnosed with allergic contact dermatitis in the previous 15 years (between 2000 and 2015) were included in the analysis. Epidemiological (age, sex, history of atopy) and clinical (site of the lesions, allergen series applied, positive reactions, and their relevance) variables were gathered. Patch tests had been performed on 4,593 patients during the study period. Of these, 265 (6%) were children aged between 0 and 16 years. A positive reaction to at least one of the allergens tested was observed in 144 (54.3%) patients in that group. The allergens most frequently identified were the following (in decreasing order of frequency): thiomersal, cobalt chloride, colophony, paraphenylenediamine, potassium dichromate, mercury, and nickel. The sensitization was considered relevant in 177 (61.3%) cases. More than half of the children studied showed sensitization to 1 or more allergens, with a high percentage of relevant sensitizations. All children with a clinical suspicion of allergic contact dermatitis should be referred for patch testing. As no standardized test series have been developed for this age group, a high level of clinical suspicion and knowledge of the allergens most commonly involved are required when selecting the allergens to be tested. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform

PubMed Central

Schachtschneider, Kyle M.; Schwind, Regina M.; Newson, Jordan; Kinachtchouk, Nickolas; Rizko, Mark; Mendoza-Elias, Nasya; Grippo, Paul; Principe, Daniel R.; Park, Alex; Overgaard, Nana H.; Jungersen, Gregers; Garcia, Kelly D.; Maker, Ajay V.; Rund, Laurie A.; Ozer, Howard; Gaba, Ron C.; Schook, Lawrence B.

2017-01-01

Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model—the Oncopig Cancer Model (OCM)—as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D, the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice. PMID:28879168

Use and perceptions of information among family physicians: sources considered accessible, relevant, and reliable.

PubMed

Kosteniuk, Julie G; Morgan, Debra G; D'Arcy, Carl K

2013-01-01

The research determined (1) the information sources that family physicians (FPs) most commonly use to update their general medical knowledge and to make specific clinical decisions, and (2) the information sources FPs found to be most physically accessible, intellectually accessible (easy to understand), reliable (trustworthy), and relevant to their needs. A cross-sectional postal survey of 792 FPs and locum tenens, in full-time or part-time medical practice, currently practicing or on leave of absence in the Canadian province of Saskatchewan was conducted during the period of January to April 2008. Of 666 eligible physicians, 331 completed and returned surveys, resulting in a response rate of 49.7% (331/666). Medical textbooks and colleagues in the main patient care setting were the top 2 sources for the purpose of making specific clinical decisions. Medical textbooks were most frequently considered by FPs to be reliable (trustworthy), and colleagues in the main patient care setting were most physically accessible (easy to access). When making specific clinical decisions, FPs were most likely to use information from sources that they considered to be reliable and generally physically accessible, suggesting that FPs can best be supported by facilitating easy and convenient access to high-quality information.

Systematic reviews: guidance relevant for studies of older people

PubMed Central

Wilkinson, Tim; Dodds, Richard M.; Ioannidis, John P. A.

2017-01-01

Abstract Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written—and if possible published—before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews. PMID:28655142

Microsoft health patient journey demonstrator.

PubMed

Disse, Kirsten

2008-01-01

As health care becomes more reliant on electronic systems, there is a need to standardise display elements to promote patient safety and clinical efficiency. The Microsoft Health Common User Interface (MSCUI) programme, developed by Microsoft and the National Health Service (NHS) was born out of this need and creates guidance and controls designed to increase patient safety and clinical effectiveness through consistent interface treatments. The Microsoft Health Patient Journey Demonstrator is a prototype tool designed to provide exemplar implementations of MSCUI guidance on a Microsoft platform. It is a targeted glimpse at a visual interface for the integration of health-relevant information, including electronic medical records. We built the demonstrator in Microsoft Silverlight 2, our application technology which brings desktop functionality and enriched levels of user experience to health settings worldwide via the internet. We based the demonstrator on an easily recognisable clinical scenario which offered us the most scope for demonstrating MSCUI guidance and innovation. The demonstrator is structured in three sections (administration, primary care and secondary care) each of which illustrates the activities associated within the setting relevant to our scenario. The demonstrator is published on the MSCUI website www.mscui.net The MSCUI patient journey demonstrator has been successful in raising awareness and increasing interest in the CUI programme.

[Adolescent scoliosis : From deformity to treatment].

PubMed

Schulze, A; Schrading, S; Betsch, M; Quack, V; Tingart, M

2015-11-01

Scoliosis affects up to 6 % of the population. The resulting spine deformity, the increasing risk of back pain, cosmetic aspects, pulmonary disorders if the Cobb angle is > 80°, and the progress of the deformity to > 50° after the end of growth indicate non-operative or operative therapy. In daily clinical practice, the classifications of scoliosis allow the therapy to be adapted. Classifications consider deformity, topography of the scoliosis, and the age at diagnosis. This publication gives an overview of the relevant and most common classifications in the treatment of adolescent scoliosis. For evaluation, the deformity measurement on the coronary radiographic projection of the total spine (Cobb angle) is relevant to therapy. The classification of topography, form, and the sagittal profile of the deformity of the spine are useful for preoperative planning of the fusion level. Classifications that take into account the age at the time of the diagnosis of scoliosis differentiate among early onset scoliosis (younger than 10 years of age), adolescent scoliosis (up to the end of growth), and adult scoliosis. Early onset scoliosis is subdivided by age and etiology. Therapy is derived from the classification of clinical and radiological findings. Classifications that take into account clinical and radiological parameters are essential components of modern scoliosis therapy.

[Tissue engineering of urinary bladder using acellular matrix].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-04-01

Tissue engineering has become a new promising strategy for repairing damaged organs of the urinary system, including the bladder. The basic idea of tissue engineering is to integrate cellular technology and advanced bio-compatible materials to replace or repair tissues and organs. of the study is the objective reflection of the current trends and advances in tissue engineering of the bladder using acellular matrix through a systematic search of preclinical and clinical studies of interest. Relevant studies, including those on methods of tissue engineering of urinary bladder, was retrieved from multiple databases, including Scopus, Web of Science, PubMed, Embase. The reference lists of the retrieved review articles were analyzed for the presence of the missing relevant publications. In addition, a manual search for registered clinical trials was conducted in clinicaltrials.gov. Following the above search strategy, a total of 77 eligible studies were selected for further analysis. Studies differed in the types of animal models, supporting structures, cells and growth factors. Among those, studies using cell-free matrix were selected for a more detailed analysis. Partial restoration of urothelium layer was observed in most studies where acellular grafts were used for cystoplasty, but no the growth of the muscle layer was observed. This is the main reason why cellular structures are more commonly used in clinical practice.

Infusion of solutions of pre-irradiated components in rats.

PubMed

Pappas, Georgina; Arnaud, Francoise; Haque, Ashraful; Kino, Tomoyuki; Facemire, Paul; Carroll, Erica; Auker, Charles; McCarron, Richard; Scultetus, Anke

2016-06-01

The objective of this study was to conduct a 14-day toxicology assessment for intravenous solutions prepared from irradiated resuscitation fluid components and sterile water. Healthy Sprague Dawley rats (7-10/group) were instrumented and randomized to receive one of the following Field IntraVenous Resuscitation (FIVR) or commercial fluids; Normal Saline (NS), Lactated Ringer's, 5% Dextrose in NS. Daily clinical observation, chemistry and hematology on days 1,7,14, and urinalysis on day 14 were evaluated for equivalence using a two sample t-test (p<0.05). A board-certified pathologist evaluated organ histopathology on day 14. Equivalence was established for all observation parameters, lactate, sodium, liver enzymes, creatinine, WBC and differential, and urinalysis values. Lack of equivalence for hemoglobin (p=0.055), pH (p=0.0955), glucose (p=0.0889), Alanine-Aminotransferase (p=0.1938), albumin (p=0.1311), and weight (p=0.0555, p=0.1896), was deemed not clinically relevant due to means within physiologically normal ranges. Common microscopic findings randomly distributed among animals of all groups were endocarditis/myocarditis and pulmonary lesions. These findings are consistent with complications due to long-term catheter use and suggest no clinically relevant differences in end-organ toxicity between animals infused with FIVR versus commercial fluids. Copyright © 2016 Elsevier GmbH. All rights reserved.

Use and perceptions of information among family physicians: sources considered accessible, relevant, and reliable

PubMed Central

Kosteniuk, Julie G.; Morgan, Debra G.; D'Arcy, Carl K.

2013-01-01

Objectives: The research determined (1) the information sources that family physicians (FPs) most commonly use to update their general medical knowledge and to make specific clinical decisions, and (2) the information sources FPs found to be most physically accessible, intellectually accessible (easy to understand), reliable (trustworthy), and relevant to their needs. Methods: A cross-sectional postal survey of 792 FPs and locum tenens, in full-time or part-time medical practice, currently practicing or on leave of absence in the Canadian province of Saskatchewan was conducted during the period of January to April 2008. Results: Of 666 eligible physicians, 331 completed and returned surveys, resulting in a response rate of 49.7% (331/666). Medical textbooks and colleagues in the main patient care setting were the top 2 sources for the purpose of making specific clinical decisions. Medical textbooks were most frequently considered by FPs to be reliable (trustworthy), and colleagues in the main patient care setting were most physically accessible (easy to access). Conclusions: When making specific clinical decisions, FPs were most likely to use information from sources that they considered to be reliable and generally physically accessible, suggesting that FPs can best be supported by facilitating easy and convenient access to high-quality information. PMID:23405045

Enhancing the supportive care of parents with advanced cancer: development of a self-directed educational manual.

PubMed

Turner, Jane; Clavarino, Alexandra; Yates, Patsy; Hargraves, Maryanne; Connors, Veronica; Hausmann, Sue

2008-08-01

Diagnosing and treating young patients with cancer can be stressful for health professionals; however, when the prognosis is poor and the patient has dependent children, even experienced clinicians can feel distressed and helpless. Parents with advanced cancer commonly express anxiety about the impact of the disease on their children, yet health professionals often feel unable to respond constructively because of lack of training, or concern that discussion about such difficult issues will compound parental distress. In response to this problem, an educational manual has been devised to assist oncology staff to better understand the emotional impact of parental advanced cancer, encompassing information about specific reactions of children, including strategies to help children and families cope. This paper describes the development and content of the resource which provides clinically relevant information and evidence-based recommendations to guide supportive care. The manual differs from the more traditional didactic resources in that it examines the very personal impact for professionals working with parents with advanced disease, encouraging reflection and engages the reader in clinical exercises which encourage active learning and application of knowledge into authentic clinical contexts. Although the manual is designed primarily for nurses, it is clear that much of the information is relevant for all health professionals involved in the care of parents with advanced cancer.

21 CFR 1271.75 - How do I screen a donor?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases... risk factors for and clinical evidence of relevant cell-associated communicable disease agents and... having either of the following: (1) A risk factor for or clinical evidence of any of the relevant...

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

PubMed

Debruyne, Philip R; Johnson, Philip J; Pottel, Lies; Daniels, Susanna; Greer, Rachel; Hodgkinson, Elizabeth; Kelly, Stephen; Lycke, Michelle; Samol, Jens; Mason, Julie; Kimber, Donna; Loucaides, Eileen; Parmar, Mahesh Kb; Harvey, Sally

2015-06-01

Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research. © The Author(s) 2015.

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Species diversity of Aspergillus section Versicolores in clinical samples and antifungal susceptibility.

PubMed

Siqueira, João Paulo Zen; Sutton, Deanna A; García, Dania; Gené, Josepa; Thomson, Pamela; Wiederhold, Nathan; Guarro, Josep

2016-11-01

Aspergillus section Versicolores includes species of clinical relevance and many others that have been poorly studied but are occasionally found in clinical samples. The aim of this study was to investigate, using a multilocus phylogenetic approach, the spectrum of species of the section Versicolores and to determine their in vitro antifungal susceptibility. The study was based on a set of 77 clinical isolates from different USA medical centres, which had been previously identified as belonging to this section. The genetic markers used were internal transcribed spacer (ITS), β-tubulin (BenA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2), and the drugs tested, following the CLSI guidelines, were amphotericin B (AMB), itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, terbinafine (TBF), and flucytosine (5FC). The most frequent species were Aspergillus sydowii (26 %), Aspergillus creber (22 %), and Aspergillus amoenus (18.2 %), followed by Aspergillus protuberus (13 %), Aspergillus jensenii (10.4 %), and Aspergillus tabacinus (5.2 %); while Aspergillus cvjetkovicii, Aspergillus fructus, Aspergillus puulaauensis, and Aspergillus versicolor were represented by only one isolate each (1.3 %). This is the first time that A. jensenii and A. puulaauensis have been reported from clinical samples. Considering the high number of isolates identified as belonging to this fungal group in this study, its clinical relevance should not be overlooked. Aspergillus versicolor, traditionally considered one of the most common species in this section in a clinical setting, was only rarely recovered in our study. The in vitro antifungal results showed that echinocandins and TBF were the most potent drugs, the azoles showed variable results, AMB was poorly active, and 5FC was the less active. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

The effectiveness of the bone bridge transtibial amputation technique: A systematic review of high-quality evidence.

PubMed

Kahle, Jason T; Highsmith, M Jason; Kenney, John; Ruth, Tim; Lunseth, Paul A; Ertl, Janos

2017-06-01

This literature review was undertaken to determine if commonly held views about the benefits of a bone bridge technique are supported by the literature. Four databases were searched for articles pertaining to surgical strategies specific to a bone bridge technique of the transtibial amputee. A total of 35 articles were identified as potential articles. Authors included methodology that was applied to separate topics. Following identification, articles were excluded if they were determined to be low quality evidence or not pertinent. Nine articles were identified to be pertinent to one of the topics: Perioperative Care, Acute Care, Subjective Analysis and Function. Two articles sorted into multiple topics. Two articles were sorted into the Perioperative Care topic, 4 articles sorted into the Acute Care topic, 2 articles into the Subjective Analysis topic and 5 articles into the Function topic. There are no high quality (level one or two) clinical trials reporting comparisons of the bone bridge technique to traditional methods. There is limited evidence supporting the clinical outcomes of the bone bridge technique. There is no agreement supporting or discouraging the perioperative and acute care aspects of the bone bridge technique. There is no evidence defining an interventional comparison of the bone bridge technique. Current level III evidence supports a bone bridge technique as an equivalent option to the non-bone bridge transtibial amputation technique. Formal level I and II clinical trials will need to be considered in the future to guide clinical practice. Clinical relevance Clinical Practice Guidelines are evidence based. This systematic literature review identifies the highest quality evidence to date which reports a consensus of outcomes agreeing bone bridge is as safe and effective as alternatives. The clinical relevance is understanding bone bridge could additionally provide a mechanistic advantage for the transtibial amputee.

Ticks and tick-borne diseases: a One Health perspective.

PubMed

Dantas-Torres, Filipe; Chomel, Bruno B; Otranto, Domenico

2012-10-01

Tick-borne diseases are common occurrences in both the medical and veterinary clinical settings. In addition to the constraints related to their diagnosis and clinical management, the control and prevention of these diseases is often difficult, because it requires the disruption of a complex transmission chain, involving vertebrate hosts and ticks, which interact in a constantly changing environment. We provide a contemporary review of representative tick-borne diseases of humans and discuss aspects linked to their medical relevance worldwide. Finally, we emphasize the importance of a One Health approach to tick-borne diseases, calling physicians and veterinarians to unify their efforts in the management of these diseases, several of which are zoonoses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improving Atrial Fibrillation Therapy: Is There a Gene for That?

PubMed

Hucker, William J; Hanley, Alan; Ellinor, Patrick T

2017-04-25

Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Opisthorchiasis and viral hepatitis b: clinical cases.

PubMed

Kotelevska, Tetiana M; Pryimenko, Nataliia O; Dubynska, Galyna M; Iziumska, Olena M; Bodnar, Vadym A

2018-01-01

Introduction: Among the cases of biohelminthosis, which are registered in Ukraine, opisthorchiasis is the most common and constitutes the second largest centre in Europe. Due to the growth of migration processes and global tourism, opisthorchiasis is becoming increasingly relevant for the countries of the European Union and the United States. Under modern conditions, the clinical course of many infectious and parasitic diseases has changed. The aim: The present paper discusses and analyzes the cases of opisthorchiasis and hepatitis B virus which are challenging in terms of diagnostics and choice of treatment tactics. Conclusion: The course of acute infections, the formation of results and the effectiveness of treatment are influenced by a number of factors, among which mixed infections are of particular interest.

Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

PubMed Central

Sartor, R. Balfour

2015-01-01

Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

The genetics and biology of KRAS in lung cancer

PubMed Central

Westcott, Peter M. K.; To, Minh D.

2013-01-01

Mutational activation of KRAS is a common oncogenic event in lung cancer and other epithelial cancer types. Efforts to develop therapies that counteract the oncogenic effects of mutant KRAS have been largely unsuccessful, and cancers driven by mutant KRAS remain among the most refractory to available treatments. Studies undertaken over the past decades have produced a wealth of information regarding the clinical relevance of KRAS mutations in lung cancer. Mutant Kras-driven mouse models of cancer, together with cellular and molecular studies, have provided a deeper appreciation for the complex functions of KRAS in tumorigenesis. However, a much more thorough understanding of these complexities is needed before clinically effective therapies targeting mutant KRAS-driven cancers can be achieved. PMID:22776234

Managing pregnancy and delivery in women with sexual pain disorders.

PubMed

Rosenbaum, Talli Y; Padoa, Anna

2012-07-01

Vaginismus and dyspareunia most commonly affect women in their childbearing years, yet sexual function, and not childbirth, has been the focus of most research. The aim of this study is to discuss pregnancy and birth outcomes in women with sexual pain disorders (SPDs) and address practical concerns of patients and practitioners regarding management during pregnancy, pelvic examination, labor, and delivery. Review of the relevant literature and recommendations based on clinical expertise of the authors. A review of SPD, conception, and birth outcomes is provided as well as clinical recommendations for prenatal, labor, and delivery management of women with SPD. Practitioners involved in obstetrical care should be knowledgeable about SPD and provide appropriate modifications and interventions. © 2012 International Society for Sexual Medicine.

Dolichandrone platycalyx: New entomophilous pollen--A report on pollen sensitization in allergic individuals.

PubMed

Mridula, P A; Mahesh, P A; Abraham, Jacob N; Amrutha, D H; Agashe, S N; Sitesh, Roy; Vedanthan, P K

2011-01-01

Dolichandrone platycalyx, commonly known as Nile trumpet tree, is believed to have originated in East Africa. However, this and the variants of this tree are found in Europe, Asia, and America (California and Florida). The tree mostly grows in tropical climates, but temperate species are also found. This study was designed to evaluate the allergenicity of D. platycalyx, one of the most common entomophilous avenue trees in Karnataka state, and to determine the pollen production of D. platycalyx. All of the patients with allergic rhinitis and asthma attending a tertiary care center in South India during August 2007 to March 2008 underwent a detailed clinical evaluation and skin-prick testing to common allergens along with D. platycalyx. Control subjects without any symptoms of respiratory allergy also underwent skin testing. The pollen counts were determined for a mature unopened flower of D. platycalyx. A total of 317 subjects with respiratory allergy and 30 controls were included in the study. A significant percentage (16.1%) of patients evaluated were observed to be sensitive to Dolichandrone pollen extract by skin-prick testing, whereas none of the control subjects were found to be sensitized. D. platycalyx was the fourth most common sensitizer after Parthenium hysterophorus, Prosopis juliflora, and Artemesia vulgaris. D. platycalyx was found to be a moderate pollen producer at 66,000 pollens/flower. Sensitization to D. platycalyx is common in subjects with respiratory allergies. The clinical relevance of this sensitization and other entomophilous plants needs additional study.

Impact of Federal Regulatory Changes on Clinical Pharmacology and Drug Development: the Common Rule and the 21st Century Cures Act.

PubMed

Burris, James F; Puglisi, J Thomas

2017-10-05

The Federal Policy for the Protection of Human Subjects, generally referred to as the "Common Rule," is the basis for the human research protection policies of 16 signatory federal agencies and governs virtually all federally funded research involving humans. The Common Rule was originally published in 1991. It has been recognized that changes to the Common Rule are needed to accommodate changes in the research environment and advances in information technology. The Department of Health & Human Services (HHS) issued an Advance Notice of Proposed Rulemaking in the Federal Register in 2011 and a Notice of Proposed Rulemaking in 2015. The final rule was published on January 19, 2017, just prior to the change in presidential administrations. The long gestation of the new Common Rule reflects the difficulty of obtaining consensus on a number of controversial issues. HHS received more than 2100 public comments on the proposed rule. The revised rule introduces important changes that may be particularly relevant to clinical pharmacology research and drug development. These include: (1) revised informed consent requirements, (2) procedures for "broad consent" to facilitate secondary research use of identifiable private information and/or biological specimens, (3) a mandate to promote review by a single institutional review board (IRB) for oversight of federally funded domestic cooperative research involving multiple institutions, (4) expansion of the categories of exempt research, and (5) removal of the requirement for annual continuing IRB review of research in which the remaining activities are limited to data analysis or accessing clinical follow-up data. Also noteworthy are proposed revisions not included in the final rule, including one to extend the Common Rule to multicenter studies that are not federally funded and one to require informed consent for research use of de-identified biological specimens. Major changes could also be coming for approval of new drugs by the Food and Drug Administration (FDA), although it is not a signatory to the Common Rule. The 21st Century Cures Act, which became law in December 2016, enables faster drug approvals by expanding the kinds of evidence, beyond traditional clinical trials, that the FDA can consider when reviewing new drug applications. For example, the law allows greater use of surrogate markers and data from "real-world experience" to evaluate a drug's efficacy. The Cures Act requires HHS and the FDA to harmonize differences between the Common Rule and FDA regulations for protection of human subjects in research. © 2017, The American College of Clinical Pharmacology.

Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value

PubMed Central

Berlth, Felix; Bollschweiler, Elfriede; Drebber, Uta; Hoelscher, Arnulf H; Moenig, Stefan

2014-01-01

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer. PMID:24914328

The maternal health clinic: an initiative for cardiovascular risk identification in women with pregnancy-related complications.

PubMed

Cusimano, Maria C; Pudwell, Jessica; Roddy, Michelle; Cho, Chan-Kyung Jane; Smith, Graeme N

2014-05-01

Women who develop certain common pregnancy complications have a greater chance of developing cardiovascular disease (CVD) later in life. However, most health care providers do not provide postpartum cardiovascular risk counselling or follow-up. The Maternal Health Clinic was established to address this gap in care. It targets women at increased risk of CVD to inspire lifestyle changes, encourage long-term follow-up, and initiate primary prevention. Here, we summarize results from the first 17 months of completed clinic visits. Patients experiencing at least one relevant complication in their index pregnancy were referred to the Maternal Health Clinic through standard postpartum order sheets. Patients underwent a complete assessment including screening history, physical examination, fasting bloodwork, and urinalysis. Lifetime and 30-year CVD risk estimates, along with a metabolic syndrome calculation, were determined for each patient. Complications most commonly leading to referral were gestational diabetes or impaired glucose tolerance (32.7%), preeclampsia (29.3%), preterm birth (29.3%), and gestational hypertension (19.6%). The clinic analysis group (n = 92) was compared with a healthy control group from the PreEclampsia New Emerging Team study (n = 118). Patients in the clinic analysis group had significantly increased lifetime and 30-year CVD risk estimates compared with healthy controls (P < .0001). Furthermore, 17.4% of the clinic analysis group had metabolic syndrome, compared with 6.78% of healthy controls (P < .05). This study demonstrates that the Maternal Health Clinic accurately identifies postpartum patients that have underlying cardiovascular risks which make them susceptible to CVD. The clinic may serve as an effective primary prevention strategy. Copyright © 2014 Mosby, Inc. All rights reserved.

Naloxegol, an opioid antagonist with reduced CNS penetration: Mode-of-action and human relevance for rat testicular tumours.

PubMed

Andersson, Håkan; Mitchard, Terri; Johnson, Nakpangi; Floettmann, Eike

2017-08-15

Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed. A genotoxic mechanism was ruled out following negative results in the Ames, mouse lymphoma, and micronucleus assays. An effect on androgen metabolism was excluded since the treatment of rats with naloxegol for 14days did not result in any induction of CYP protein levels. It was demonstrated that administration of centrally restricted opioid antagonists naloxegol or methylnaltrexone at high doses induced an increase in LH release with no clear increase in testosterone, in contrast to the centrally acting opioid antagonist naloxone, which showed marked increases in both LH and testosterone. LCT due to increased LH stimulation is common in rats but not documented in humans. Collectively, the lack of genotoxicity signal, the lack of androgen effect, the increase in LH secretion in rats, which is no considered to be relevant for LCT formation in humans, and high margins to clinical exposures, the observed increase in LCT in the rat is not expected to be clinically relevant. Copyright © 2017 Elsevier Inc. All rights reserved.

Diarrhoea in the enterally fed patient

PubMed Central

Bowling, T E

2010-01-01

Diarrhoea complicating enteral feeding is very common in all clinical settings. The major risk factor is the use of concomitant antibiotics. The underlying mechanisms for the diarrhoea mainly relate to alterations in the colonic flora and physiological responses to the mode of feed delivery although a clear understanding of what is actually happening in vivo remains elusive. Management of diarrhoea includes rationalising medications, excluding relevant comorbidity and using antidiarrhoeal medications. Altering the method and site of feed delivery—for example, continuous to bolus, gastric to postpyloric—can also be tried in the more difficult cases. PMID:28839565

Sarcopenia: Beyond Muscle Atrophy and into the New Frontiers of Opportunistic Imaging, Precision Medicine, and Machine Learning.

PubMed

Lenchik, Leon; Boutin, Robert D

2018-07-01

As populations continue to age worldwide, the impact of sarcopenia on public health will continue to grow. The clinically relevant and increasingly common diagnosis of sarcopenia is at the confluence of three tectonic shifts in medicine: opportunistic imaging, precision medicine, and machine learning. This review focuses on the state-of-the-art imaging of sarcopenia and provides context for such imaging by discussing the epidemiology, pathophysiology, consequences, and future directions in the field of sarcopenia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biliary pain--work-up and management in general practice.

PubMed

Crawford, Michael

2013-07-01

Pain arising from the gallbladder and biliary tree is a common clinical presentation. Differentiation from other causes of abdominal pain can sometimes be difficult. This article discusses the work-up, management and after care of patients with biliary pain. The role for surgery for gallstones and gallbladder polyps is described. Difficulties in the diagnosis and management of gallbladder pain are discussed. Intra- and post-operative complications are described, along with their management. The issue of post-operative pain in particular is examined, focusing on the timing of the pain and the relevant investigations.

Cerebrotendinous xanthomatosis.

PubMed

van Hellenberg Hubar, J L; Joosten, E M; Wevers, R A

1992-01-01

Cerebrotendinous xanthomatosis (CTX) is a familial sterol storage disease based on an inborn error of metabolism involving bile acid synthesis. Predominant clinical features are a chronic progressive neurological syndrome, mental deterioration, bilateral cataract and xanthomas. The presence of xanthomas usually leads to the diagnosis, and the reverse is probably also true: without xanthomas the diagnosis will often not be made. CTX may therefore be less rare than commonly thought, and the incidence of xanthomas in CTX may be overestimated. Four cases without xanthomas among the presenting symptoms are described, and the relevance of xanthomas in CTX is discussed.

Impact of Serum Vancomycin Trough Levels in the Treatment of Central Nervous System Shunt Infections Caused by Coagulase-Negative Staphylococci.

PubMed

Gibson, Ashley; Kaplan, Sheldon L; Vallejo, Jesus G

2018-04-26

Coagulase-negative staphylococci (CoNS) are a common cause of pediatric ventricular shunt infections. The Infectious Diseases Society of America recommends vancomycin serum troughs of 15-20 µg/mL when treating CoNS shunt infections in adult patients. We report a series of pediatric cases of CoNS shunt infections in which clinical cure was obtained with troughs < 15 µg/mL. These findings question the relevance of this recommendation in pediatric patients. © 2018 S. Karger AG, Basel.

A Summary of Important Documents in the Field of Research Ethics

PubMed Central

Fischer, Bernard A

2006-01-01

Today's researchers are obligated to conduct their studies ethically. However, it often seems a daunting task to become familiar with the important ethical codes required to do so. The purpose of this article is to examine the content of those ethical documents most relevant to the biomedical researcher. Documents examined include the Nuremberg Code, the Declaration of Helsinki, Henry Beecher's landmark paper, the Belmont Report, the U.S. Common Rule, the Guideline for Good Clinical Practice, and the National Bioethics Advisory Commission's report on research protections for the mentally ill. PMID:16192409

Inhibition of the high affinity myo-inositol transport system: a common mechanism of action of antibipolar drugs?

PubMed

Lubrich, B; van Calker, D

1999-10-01

The mechanism of action of antibipolar drugs like lithium, carbamazepine, and valproate that are used in the treatment of manic-depressive illness, is unknown. Lithium is believed to act through uncompetitive inhibition of inositolmonophosphatase, which results in a depletion of neural cells of inositol and a concomitant modulation of phosphoinositol signaling. Here, we show that lithium ions, carbamazepine, and valproate, but not the tricyclic antidepressant amitriptyline, inhibit at therapeutically relevant concentrations and with a time course similar to their clinical actions the high affinity myo-inositol transport in astrocyte-like cells and downregulate the level of the respective mRNA. Inhibition of inositol uptake could thus represent an additional pathway for inositol depletion, which might be relevant in the mechanism of action of all three antibipolar drugs.

Skin signs of primary immunodeficiencies: how to find the genes to check.

PubMed

Ettinger, M; Schreml, J; Wirsching, K; Berneburg, M; Schreml, S

2018-02-01

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs. © 2017 British Association of Dermatologists.

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome – Review of 5 cases

PubMed Central

PLAIASU, Vasilica; OCHIANA, Diana; MOTEI, Gabriela; ANCA, Ioana; GEORGESCU, Adrian

2010-01-01

ABSTRACT Introduction: Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. Materials and methods: In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). Discussion: All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. Conclusion: The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management. PMID:21977150

Optimizing the use of video-tapes of clinical sessions: the data-mining approach for scale construction and theory building for bereaved persons in Hong Kong.

PubMed

Chow, Amy Yin Man

2010-01-01

Video-taping clinical sessions is a common practice among social workers so that the tapes may be used for clinical supervision and reviewed with the individuals or families involved. They are usually underused for research purposes. This article reports on an innovative research method using such tapes as a basis for clinical data mining to explore the bereavement experience of Chinese people in Hong Kong. Using this data, a rich item pool, containing both negative and positive reactions, was generated to allow the development of a culturally relevant measurement tool of grief reactions. The data also facilitated theory building in the area of grief and bereavement. This study extended the use of video-tapes in clinical sessions for research purposes and helped to collect reliable and timely data in a non-intrusive way. It has also advanced the use of quantitative data in the clinical data-mining approach. The study encouraged collaboration between clinicians and researchers to develop knowledge and skills about their special target group of clients.

The clinical management of awake bruxism.

PubMed

Goldstein, Ronald E; Auclair Clark, Wendy

2017-06-01

Awake bruxism is a common clinical condition that often goes undetected, often leading to pain or damaged teeth and restorations. The authors searched electronic databases regarding the treatment and effects of awake bruxism compared with those of sleep bruxism. The authors used the search terms diurnal bruxism and oral parafunction. The authors combined information from relevant literature with clinical experience to establish a recommended protocol for diagnosis and treatment. The authors found articles regarding the diagnosis and treatment of bruxism. The authors combined information from the articles with a review of clinical cases to establish a treatment protocol for awake bruxism. Literature and clinical experience indicate a lack of patient awareness and, thus, underreporting of awake bruxism. As a result, myriad dental consequences can occur from bruxism. The authors propose a need for increased awareness, for both patients and professionals, particularly of the number of conditions related to awake bruxism. Clinicians should look for clinical signs and symptoms of awake bruxism and use minimally invasive treatment modalities. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Clinical relevance of findings in trials of CBT for depression.

PubMed

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients.

PubMed

Choi, J H; Park, D J; Kang, J H; Yim, Y R; Lee, K E; Lee, J W; Wen, L; Kim, T J; Park, Y W; Lee, J K; Lee, S S

2015-10-01

We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at ≤ 18 years), adult-onset SLE (ASLE, diagnosed at 19-50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjögren's syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and anti-nucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjögren's syndrome, at disease onset. © The Author(s) 2015.

On-Orbit Prospective Echocardiography on International Space Station

NASA Technical Reports Server (NTRS)

Hamilton, Douglas R.; Sargsyan, Ashot E.; Martin, David; Garcia, Kathleen M.; Melton, Shannon; Feiverson, Alan; Dulchavsky, Scott A.

2010-01-01

A number of echocardiographic research projects and experiments have been flown on almost every space vehicle since 1970, but validation of standard methods and the determination of Space Normal cardiac function has not been reported to date. Advanced Diagnostics in Microgravity (ADUM) -remote guided echocardiographic technique provides a novel and effective approach to on-board assessment of cardiac physiology and structure using a just-in-time training algorithm and real-time remote guidance aboard the International Space Station (ISS). The validation of remotely guided echocardiographic techniques provides the procedures and protocols to perform scientific and clinical echocardiography on the ISS and the Moon. The objectives of this study were: 1.To confirm the ability of non-physician astronaut/cosmonaut crewmembers to perform clinically relevant remotely guided echocardiography using the Human Research Facility on board the ISS. 2.To compare the preflight, postflight and in-flight echocardiographic parameters commonly used in clinical medicine.

Implementing elements of evidence-based practice into scientist-practitioner training at the University of Nebraska-Lincoln.

PubMed

DiLillo, David; McChargue, Dennis

2007-07-01

Evidence-based practice (EBP) has become the predominant model of training and is emerging as a common model of practice for many non-psychology health care professions. Recognizing the relevance of EBP to psychology, the American Psychological Association (APA) developed and endorsed an official policy statement on EBP for the practice of professional psychology. There is now a pressing need to consider ways that EBP can inform scientist-practitioner training. The present article proposes clinical competencies associated with the practice of EBP, and describes initial efforts to implement elements of EBP into training at the University of Nebraska-Lincoln. These efforts have occurred in both the classroom and practicum training experiences, and are geared toward helping students become more effective users of the evidence base through their clinical work. Challenges to the implementation of EBP in clinical psychology training are discussed as well.

Respiratory infections due to nontuberculous mycobacterias.

PubMed

Máiz Carro, Luis; Barbero Herranz, Esther; Nieto Royo, Rosa

2018-03-09

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Tunnels and grooves for supraclavicular nerves within the clavicle: review of the literature and clinical impact.

PubMed

Natsis, Konstantinos; Totlis, Trifon; Chorti, Angeliki; Karanassos, Marinos; Didagelos, Matthaios; Lazaridis, Nikolaos

2016-08-01

Perforation of the clavicle by supraclavicular nerves is a common anatomical variation. This variation has been reported in several studies based on post-mortem, surgical and radiologic findings, with an overall frequency between 1 and 6.6 %. The penetrating branch passes either through a bony tunnel or a groove on the superior surface of the bone. Entrapment neuropathy of the perforating branch is a documented clinical entity reported in the literature. The intraosseous course of the supraclavicular nerves makes them vulnerable to injury in case of clavicular fractures or during surgical manipulations of these fractures. Furthermore, this variation should be taken into account during the interpretation of chest and shoulder radiographs. The purpose of the current study is to perform an extended review of the relevant literature, highlighting the clinical impact of this variation, as well as to incorporate our own findings into them.

Inconsistent Results of Diagnostic Tools Hamper the Differentiation between Bee and Vespid Venom Allergy

PubMed Central

Sturm, Gunter J.; Jin, Chunsheng; Kranzelbinder, Bettina; Hemmer, Wolfgang; Sturm, Eva M.; Griesbacher, Antonia; Heinemann, Akos; Vollmann, Jutta; Altmann, Friedrich; Crailsheim, Karl; Focke, Margarete; Aberer, Werner

2011-01-01

Background Double sensitization (DS) to bee and vespid venom is frequently observed in the diagnosis of hymenoptera venom allergy, but clinically relevant DS is rare. Therefore it is sophisticated to choose the relevant venom for specific immunotherapy and overtreatment with both venoms may occur. We aimed to compare currently available routine diagnostic tests as well as experimental tests to identify the most accurate diagnostic tool. Methods 117 patients with a history of a bee or vespid allergy were included in the study. Initially, IgE determination by the ImmunoCAP, by the Immulite, and by the ADVIA Centaur, as well as the intradermal test (IDT) and the basophil activation test (BAT) were performed. In 72 CAP double positive patients, individual IgE patterns were determined by western blot inhibition and component resolved diagnosis (CRD) with rApi m 1, nVes v 1, and nVes v 5. Results Among 117 patients, DS was observed in 63.7% by the Immulite, in 61.5% by the CAP, in 47.9% by the IDT, in 20.5% by the ADVIA, and in 17.1% by the BAT. In CAP double positive patients, western blot inhibition revealed CCD-based DS in 50.8%, and the CRD showed 41.7% of patients with true DS. Generally, agreement between the tests was only fair and inconsistent results were common. Conclusion BAT, CRD, and ADVIA showed a low rate of DS. However, the rate of DS is higher than expected by personal history, indicating that the matter of clinical relevance is still not solved even by novel tests. Furthermore, the lack of agreement between these tests makes it difficult to distinguish between bee and vespid venom allergy. At present, no routinely employed test can be regarded as gold standard to find the clinically relevant sensitization. PMID:21698247

A reappraisal of adult thoracic and abdominal surface anatomy in Iranians in vivo using computed tomography.

PubMed

Pak, Neda; Patel, Shilpan G; Hashemi Taheri, Amir P; Hashemi, Fariba; Eftekhari Vaghefi, Raana; Naybandi Atashi, Sara; Mirjalili, S Ali

2016-03-01

Surface anatomy is a core component of human anatomy in clinical practice. It allows clinicians to assess patients accurately and quickly; however, recent studies have revealed variability among individuals and ethnicities. The aim of this study is to investigate possible variations in adult thoracic and abdominal surface anatomy landmarks in an Iranian population. This study used 100 thoracoabdominal CT scans (mean age: 47 ± 17 years, age range: 20-77 years, 47% females), noted the most common locations of clinically relevant surface markings, and analyzed correlations between these variables and age or gender. While many common surface markings in Iranians were consistent with the evidence-based literature, there were some differences. In relation to the corresponding segments of the vertebral column, the superior vena cava formation and the lower border of the pleura adjacent to the vertebral column and right kidney tended to be at higher levels in adult Iranians than a Caucasian population. There were also discrepancies between the Iranian population and commonly-referenced medical textbooks and recent evidence-based literature concerning the vertebral levels of the diaphragmatic openings of the esophagus, aorta, and inferior vena cava. This study emphasizes the need to consider evidence-based reappraisals of surface anatomy to guide clinical practice. Much of our current knowledge of surface anatomy is based on older studies of cadavers rather than living people, and does not take ethnic and individual variations into consideration. © 2015 Wiley Periodicals, Inc.

Role of laser therapy in benign prostate hyperplasia (BPH)

NASA Astrophysics Data System (ADS)

de Riese, Werner T.; Sharpe, Brent A.; Aronoff, David B.; Mittemeyer, Bernhard T.

2001-05-01

Benign prostatic hyperplasia (BPH) is a common disease in males older than 50 years of age. 75-80% of this population is considered to have some degree of BPH causing clinical symptoms and requiring urological treatment. Transurethral resection of the prostate (TUR-P) is currently the standard surgical treatment modality for BPH. In an attempt to minimize the need for hospitalization and the associated perioperative and postoperative morbidity, alternatives have been sought. Various types of laser techniques such as interstitial laser coagulation and side-firing technology have been proposed. Numerous studies have shown that laser procedures safely and effectively reduce the volume of the prostate. Intra- and postoperative bleeding are nearly unknown complications for laser procedures, whereas this is the most relevant complication for the TUR-P. Due to significant tissue edema after laser treatment, patients commonly show delayed time to void adequately and, therefore, catheter drainage is often necessary for 3 to 21 days. Retrograde ejaculation is reported to occur less (0- 10%) compared to TUR-P (greater than 60%). Urinary tract infections are very common after interstitial laser coagulation. Although not many long-term clinical data are available, various studies have shown that BPH patients improve in symptom score, flow rate and post-void residual up to 3 years after laser treatment. This paper presents a concise review of efficacy, advantages and disadvantages of the most frequently used laser techniques as well as the long-term clinical data compared to TUR-P.

New surgical treatment options in patients with benign prostate hyperplasia (BPH)

NASA Astrophysics Data System (ADS)

de Riese, Werner T. W.; Nelius, Thomas; Aronoff, David R.; Mittemeyer, Bernhard T.

2003-06-01

Benign prostatic hyperplasia (BPH) is a common disease in males older than 50 years of age. 75-80% of this population is considered to have some degree of BPH causing clinical symptoms and requiring urological treatment. Transurethral resection of the prostate (TUR-P) is currently the standard surgical treatment modality for BPH. In an attempt to minimize the need for hospitalization and the associated perioperative and postoperative morbidity, alternatives have been sought. Various types of Laser techniques such as interstitial Laser cogaulation and side-firing technology have been proposed. Numerous studies have shown that Laser procedures safely and effectively reduce the volume of the prostate. Intra- and postoperative bleeding are nearly unknown complications for Laser procedures, whereas this is the most relevant complication for the TUR-P. Due to significant tissue edema after Laser treatment, patients commonly show delayed time to void adequately, and therefore, catheter drainage is often necessary for 3 to 21 days. Retrograde ejaculation is reported to occur less (0 - 10%) compared to TUR-P (> 60%). Urinary tract infections are very common after interstitial laser coagulation. Although not many long-term clinical data are available, various studies have shown that BPH patients improve in symptom score, flow rate and post-void residual up to 3 years after Laser treatment. This paper presents a concise review of efficacy, advantages and disadvantages of the most frequently used Laser techniques as well as the long-term clinical data compared to TUR-P.

Standard Information Models for Representing Adverse Sensitivity Information in Clinical Documents.

PubMed

Topaz, M; Seger, D L; Goss, F; Lai, K; Slight, S P; Lau, J J; Nandigam, H; Zhou, L

2016-01-01

Adverse sensitivity (e.g., allergy and intolerance) information is a critical component of any electronic health record system. While several standards exist for structured entry of adverse sensitivity information, many clinicians record this data as free text. This study aimed to 1) identify and compare the existing common adverse sensitivity information models, and 2) to evaluate the coverage of the adverse sensitivity information models for representing allergy information on a subset of inpatient and outpatient adverse sensitivity clinical notes. We compared four common adverse sensitivity information models: Health Level 7 Allergy and Intolerance Domain Analysis Model, HL7-DAM; the Fast Healthcare Interoperability Resources, FHIR; the Consolidated Continuity of Care Document, C-CDA; and OpenEHR, and evaluated their coverage on a corpus of inpatient and outpatient notes (n = 120). We found that allergy specialists' notes had the highest frequency of adverse sensitivity attributes per note, whereas emergency department notes had the fewest attributes. Overall, the models had many similarities in the central attributes which covered between 75% and 95% of adverse sensitivity information contained within the notes. However, representations of some attributes (especially the value-sets) were not well aligned between the models, which is likely to present an obstacle for achieving data interoperability. Also, adverse sensitivity exceptions were not well represented among the information models. Although we found that common adverse sensitivity models cover a significant portion of relevant information in the clinical notes, our results highlight areas needed to be reconciled between the standards for data interoperability.

Structured representation for core elements of common clinical decision support interventions to facilitate knowledge sharing.

PubMed

Zhou, Li; Hongsermeier, Tonya; Boxwala, Aziz; Lewis, Janet; Kawamoto, Kensaku; Maviglia, Saverio; Gentile, Douglas; Teich, Jonathan M; Rocha, Roberto; Bell, Douglas; Middleton, Blackford

2013-01-01

At present, there are no widely accepted, standard approaches for representing computer-based clinical decision support (CDS) intervention types and their structural components. This study aimed to identify key requirements for the representation of five widely utilized CDS intervention types: alerts and reminders, order sets, infobuttons, documentation templates/forms, and relevant data presentation. An XML schema was proposed for representing these interventions and their core structural elements (e.g., general metadata, applicable clinical scenarios, CDS inputs, CDS outputs, and CDS logic) in a shareable manner. The schema was validated by building CDS artifacts for 22 different interventions, targeted toward guidelines and clinical conditions called for in the 2011 Meaningful Use criteria. Custom style sheets were developed to render the XML files in human-readable form. The CDS knowledge artifacts were shared via a public web portal. Our experience also identifies gaps in existing standards and informs future development of standards for CDS knowledge representation and sharing.

Clinical impact of migraine for the management of glaucoma patients.

PubMed

Nguyen, Bao N; Lek, Jia Jia; Vingrys, Algis J; McKendrick, Allison M

2016-03-01

Migraine is a common and debilitating primary headache disorder that affects 10-15% of the general population, particularly people of working age. Migraine is relevant to providers of clinical eye-care because migraine attacks are associated with a range of visual sensory symptoms, and because of growing evidence that the results of standard tests of visual function necessary for the diagnosis and monitoring of glaucoma (visual fields, electrophysiology, ocular imaging) can be abnormal due to migraine. These abnormalities are measureable in-between migraine events (the interictal period), despite patients being asymptomatic and otherwise healthy. This picture is further complicated by epidemiological data that suggests an increased prevalence of migraine in patients with glaucoma, particularly in patients with normal tension glaucoma. We discuss how migraine, as a co-morbidity, can confound the results and interpretation of clinical tests that form part of contemporary glaucoma evaluation, and provide practical evidence-based recommendations for the clinical testing and management of patients with migraine who attend eye-care settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

[POLYGYNAX IN THE TREATMENT OF VAGINAL INFECTIONS IN PREGNANT AND NON-PREGNANT WOMEN--CLINICAL EXPERIENCE].

PubMed

Popovski, N; Popovski, K; Nedelkovski, V

2016-01-01

Vaginal infections /VI/ represent some of the most common diseases by infection of FGS. The aim of this study is to analyze clinical and bacteriological efficacy of Polygynax in the treatment of vaginal infections and to take into account the correlation between the results of microbiological controls and reduction of clinical symptoms. The study included 100 patients, including 50 pregnant and non-pregnant 50 for a period of 3 months. All of them was diagnosed with vaginitis clinical examination, taken material from vagina for microbiological testing. The studied women was conducted targeted therapy Polygynax 12 capsules, in the form of vaginal capsules for 12 days, after which the sample control microbiology. Behind the subjective complaints of the patient and to reduce them as a result of treatment. The effective implementation of Polygynax 12 capsules is equally good as in non-pregnant and pregnant women. In a summary of the survey data to make relevant analyzes and conclusions from the results.

Clinical applications of fundus autofluorescence in retinal disease.

PubMed

Yung, Madeline; Klufas, Michael A; Sarraf, David

2016-01-01

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

Assessment of anxiety in older adults: a review of self-report measures

PubMed Central

Balsamo, Michela; Cataldi, Fedele; Carlucci, Leonardo; Fairfield, Beth

2018-01-01

With increasing numbers of older adults in the general population, anxiety will become a widespread problem in late life and one of the major causes of health care access contributing to high societal and individual costs. Unfortunately, the detection of anxiety disorders in late life is complicated by a series of factors that make it different from assessment in younger cohorts, such as differential symptom presentation, high comorbidity with medical and mental disorders, the aging process, and newly emergent changes in life circumstances. This review covers commonly and currently used self-report inventories for assessing anxiety in older adults. For each tool, psychometric data is investigated in depth. In particular, information about reliability, validity evidence based on data from clinical and nonclinical samples of older adults, and availability of age-appropriate norms are provided. Finally, guidance for clinical evaluation and future research are proposed in an effort to highlight the importance of clinical assessment in the promotion of clinically relevant therapeutic choices. PMID:29670342

Biology of advanced uveal melanoma and next steps for clinical therapeutics.

PubMed

Luke, Jason J; Triozzi, Pierre L; McKenna, Kyle C; Van Meir, Erwin G; Gershenwald, Jeffrey E; Bastian, Boris C; Gutkind, J Silvio; Bowcock, Anne M; Streicher, Howard Z; Patel, Poulam M; Sato, Takami; Sossman, Jeffery A; Sznol, Mario; Welch, Jack; Thurin, Magdalena; Selig, Sara; Flaherty, Keith T; Carvajal, Richard D

2015-03-01

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fundamentals of Clinical Pharmacology With Application for Pregnant Women.

PubMed

Patil, Avinash S; Sheng, Jessica; Dotters-Katz, Sarah K; Schmoll, Maria S; Onslow, Mitchell; Pierson, Rebecca C

2017-05-01

Medication use is common in pregnancy, yet for most medications the optimal formulation and dosage have not been described specifically for pregnant women. Often, adverse effects are only discovered anecdotally or after extensive off-label use occurs. Since pharmacologic research that includes pregnant women is sparse and animal studies are often not applicable to the human fetus, providers must use knowledge of drug behavior and normal physiologic changes of pregnancy to personalize treatment for pregnant women. In this review, we present an overview of the basic concepts of clinical pharmacology: pharmacokinetics, pharmacodynamics, and pharmacogenomics. The normal physiologic changes of pregnancy are presented as a framework to understand alterations in drug behavior. A clinical vignette that addresses 4 pregnancy scenarios involving medications-preterm birth, vaccination, herpes simplex virus infection, and codeine toxicity-is provided to illustrate application of core clinical pharmacologic concepts. Discussion of relevant literature illustrates the challenges of offering individualized pharmacologic therapy in pregnancy. © 2017 by the American College of Nurse-Midwives.

Heuristic reasoning and cognitive biases: Are they hindrances to judgments and decision making in orthodontics?

PubMed

Hicks, E Preston; Kluemper, G Thomas

2011-03-01

Studies show that our brains use 2 modes of reasoning: heuristic (intuitive, automatic, implicit processing) and analytic (deliberate, rule-based, explicit processing). The use of intuition often dominates problem solving when innovative, creative thinking is required. Under conditions of uncertainty, we default to an even greater reliance on the heuristic processing. In health care settings and other such environments of increased importance, this mode becomes problematic. Since choice heuristics are quickly constructed from fragments of memory, they are often biased by prior evaluations of and preferences for the alternatives being considered. Therefore, a rigorous and systematic decision process notwithstanding, clinical judgments under uncertainty are often flawed by a number of unwitting biases. Clinical orthodontics is as vulnerable to this fundamental failing in the decision-making process as any other health care discipline. Several of the more common cognitive biases relevant to clinical orthodontics are discussed in this article. By raising awareness of these sources of cognitive errors in our clinical decision making, our intent was to equip the clinician to take corrective action to avoid them. Our secondary goal was to expose this important area of empirical research and encourage those with expertise in the cognitive sciences to explore, through further research, the possible relevance and impact of cognitive heuristics and biases on the accuracy of orthodontic judgments and decision making. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model.

PubMed

Hao, Shao-Rui; Geng, Shi-Chao; Fan, Lin-Xiao; Chen, Jia-Jia; Zhang, Qin; Li, Lan-Juan

2017-05-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A "chaining" inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure.

Idiopathic granulomatous lobular mastitis - report of 43 cases from iran; introducing a preliminary clinical practice guideline.

PubMed

Omranipour, Ramesh; Mohammadi, S-Farzad; Samimi, Parisa

2013-12-01

We aimed to report a large series of idiopathic granulomatous lobular mastitis (IGLM) from Iran and sketch preliminary clinical practice guidelines (CPG) for approaching an inflammatory breast mass. In a retrospective records review, 43 consecutive IGLM cases were studied. Data on baseline, clinical, imaging, and pathologic characteristics were collected. The mean age of the women was 33.5 years. All but 1 were married and had given birth. 16% had a cancer-like presentation. Inflammatory signs, architectural distortion, and a nodular pattern were the most common findings clinically, mammographically and ultrasonographically, respectively. 29.5% of the pathological reports indicated necrosis which was more common in younger subjects (p = 0.016); microabscesses were associated with a shorter lactation course (p = 0.006). Corticosteroids had been used as the initial treatment modality in 51%, immunosuppressive agents had not been administered, and a 16% relapse rate was recorded. We recognized the need for a multidisciplinary approach covering radiology, oncology, and surgery to best handle diagnostic and therapeutic issues and manage relevant infections as well as the major differential diagnosis, i.e. malignancy. We hypothesized that a shorter lactation period may cause more milk stasis and extravasation and be contributory to IGLM. CPGs are needed to incorporate the needed multidisciplinary approach and to standardize IGLM care. We present one such guideline.

Idiopathic Granulomatous Lobular Mastitis – Report of 43 Cases from Iran; Introducing a Preliminary Clinical Practice Guideline

PubMed Central

Omranipour, Ramesh; Mohammadi, S-Farzad; Samimi, Parisa

2013-01-01

Summary Background We aimed to report a large series of idiopathic granulomatous lobular mastitis (IGLM) from Iran and sketch preliminary clinical practice guidelines (CPG) for approaching an inflammatory breast mass. Patients and Methods In a retrospective records review, 43 consecutive IGLM cases were studied. Data on baseline, clinical, imaging, and pathologic characteristics were collected. Results The mean age of the women was 33.5 years. All but 1 were married and had given birth. 16% had a cancer-like presentation. Inflammatory signs, architectural distortion, and a nodular pattern were the most common findings clinically, mammographically and ultrasonographically, respectively. 29.5% of the pathological reports indicated necrosis which was more common in younger subjects (p = 0.016); microabscesses were associated with a shorter lactation course (p = 0.006). Corticosteroids had been used as the initial treatment modality in 51%, immunosuppressive agents had not been administered, and a 16% relapse rate was recorded. We recognized the need for a multidisciplinary approach covering radiology, oncology, and surgery to best handle diagnostic and therapeutic issues and manage relevant infections as well as the major differential diagnosis, i.e. malignancy. Conclusion We hypothesized that a shorter lactation period may cause more milk stasis and extravasation and be contributory to IGLM. CPGs are needed to incorporate the needed multidisciplinary approach and to standardize IGLM care. We present one such guideline. PMID:24550752

Pancreatic cancer ascites xenograft–an expeditious model mirroring advanced therapeutic resistant disease

PubMed Central

Schvimer, Michael; Atias, Dikla; Halperin, Sharon; Buzhor, Ella; Raitses-Gurevich, Maria; Cohen, Keren; Pri-Chen, Sara; Wilson, Julie; Denroche, Robert E.; Lungu, Ilinca; Bartlett, John M.S.; Mbabaali, Faridah; Yarden, Yosef; Nataraj, Nishanth Belugali; Gallinger, Steven; Berger, Raanan

2017-01-01

Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations. PMID:28489577

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model*

PubMed Central

Hao, Shao-rui; Geng, Shi-chao; Fan, Lin-xiao; Chen, Jia-jia; Zhang, Qin; Li, Lan-juan

2017-01-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A “chaining” inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure. PMID:28471111

CONCEPTUAL AND METHODOLOGICAL ISSUES IN DESIGNING A RANDOMIZED CONTROLLED TREATMENT TRIAL FOR GERIATRIC BIPOLAR DISORDER: GERI-BD

PubMed Central

Young, Robert C.; Schulberg, Herbert C.; Gildengers, Ariel G.; Sajatovic, Martha; Mulsant, Benoit H.; Gyulai, Laszlo; Beyer, John; Marangell, Lauren; Kunik, Mark; Have, Thomas Ten; Bruce, Martha L.; Gur, Ruben; Marino, Patricia; Evans, Jovier D.; Reynolds, Charles F.; Alexopoulos, George S.

2010-01-01

Aim This report considers the conceptual and methodological concerns confronting clinical investigators seeking to generate knowledge regarding the tolerability and benefits of pharmacotherapy in geriatric bipolar (BP) patients. Method There is continuing need for evidence-based guidelines derived from randomized controlled trials that will enhance drug treatment of geriatric BP patients. We, therefore, present the complex conceptual and methodological choices encountered in designing a multi-site clinical trial and the decisions reached by the investigators with the intention that study findings are pertinent to, and can facilitate, routine treatment decisions. Results Guided by a literature review and input from peers, the tolerability and anti-manic effect of lithium and valproate were judged to be the key mood stabilizers to investigate with regard to treating BP I manic, mixed and hypomanic states. The patient selection criteria are intended to generate a sample that experiences common treatment needs but which also represents the variety of older patients seen in university-based clinical settings. The clinical protocol guides titratation of lithium and valproate to target serum concentrations, with lower levels allowed when necessitated by limited tolerability. The protocol emphasizes initial monotherapy. However, augmentation with risperidone is permitted after three weeks when indicated by operational criteria. Conclusions A randomized controlled trial that both investigates commonly prescribed mood stabilizers and maximizes patient participation can meaningfully address high priority clinical concerns directly relevant to the routine pharmacologic treatment of geriatric BP patients. PMID:20148867

Garlic for the common cold.

PubMed

Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

2014-11-11

Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.Objectives To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.Search methods We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).Selection criteria Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.Data collection and analysis Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.Main results In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria.This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. Authors' conclusions There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

Garlic for the common cold.

PubMed

Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

2012-03-14

Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four. To determine whether garlic (allium sativum) is effective for either the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, OLDMEDLINE (1950 to 1965), MEDLINE (January 1966 to November week 3, 2011), EMBASE (1974 to December 2011) and AMED (1985 to December 2011). Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment. Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data. Of the six trials identified as potentially relevant from our searches, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily) for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Analysis of nutrition-relevant trace elements in human blood and serum by means of total reflection X-ray fluorescence (TXRF) spectroscopy

NASA Astrophysics Data System (ADS)

Stosnach, Hagen; Mages, Margarete

2009-04-01

In clinical service laboratories, one of the most common analytical tasks with regard to inorganic traces is the determination of the nutrition-relevant elements Fe, Cu, Zn, and Se. Because of the high numbers of samples and the commercial character of these analyses, a time-consuming sample preparation must be avoided. In this presentation, the results of total reflection X-ray fluorescence measurements with a low-power system and different sample preparation procedures are compared with those derived from analysis with common methods like Atomic Absorption Spectroscopy (AAS) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The results of these investigations indicate that the optimal total reflection X-ray fluorescence analysis of the nutrition-relevant elements Fe, Cu, Zn, and Se can be performed by preparing whole blood and serum samples after dilution with ultrapure water and transferring 10 μl of internally standardized sample to an unsiliconized quartz glass sample carrier with subsequent drying in a laboratory oven. Suitable measurement time was found to be 600 s. The enhanced sample preparation by means of microwave or open digestion, in parts combined with cold plasma ashing, led to an improvement of detection limits by a factor of 2 for serum samples while for whole blood samples an improvement was only observed for samples prepared by means of microwave digestion. As the matrix elements P, S, Cl, and for whole blood Fe have a major influence on the detection limits, most probably a further enhancement of analytical quality requires the removal of the organic matrix. However, for the routine analysis of the nutrition-relevant elements, the dilution preparation was found to be sufficient.

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

PubMed

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs.

PubMed

Blum, Kenneth; Simpatico, Thomas; Febo, Marcelo; Rodriquez, Chris; Dushaj, Kristina; Li, Mona; Braverman, Eric R; Demetrovics, Zsolt; Oscar-Berman, Marlene; Badgaiyan, Rajendra D

2017-07-01

The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli's effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies.

Developing a Common Framework for Evaluating the Implementation of Genomic Medicine Interventions in Clinical Care: The IGNITE Network’s Common Measures Working Group

PubMed Central

Orlando, Lori A.; Sperber, Nina R.; Voils, Corrine; Nichols, Marshall; Myers, Rachel A.; Wu, R. Ryanne; Rakhra-Burris, Tejinder; Levy, Kenneth D.; Levy, Mia; Pollin, Toni I.; Guan, Yue; Horowitz, Carol R.; Ramos, Michelle; Kimmel, Stephen E.; McDonough, Caitrin W.; Madden, Ebony B.; Damschroder, Laura J.

2017-01-01

Purpose Implementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing GeNomics In PracTicE (IGNITE) Network’s efforts to promote: 1) a broader understanding of genomic medicine implementation research; and 2) the sharing of knowledge generated in the network. Methods To facilitate this goal the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide their approach to: identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross network analyses. Results CMG identified ten high-priority CFIR constructs as important for genomic medicine. Of those, eight didn’t have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model. Conclusion We developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field. PMID:28914267

Developing a common framework for evaluating the implementation of genomic medicine interventions in clinical care: the IGNITE Network's Common Measures Working Group.

PubMed

Orlando, Lori A; Sperber, Nina R; Voils, Corrine; Nichols, Marshall; Myers, Rachel A; Wu, R Ryanne; Rakhra-Burris, Tejinder; Levy, Kenneth D; Levy, Mia; Pollin, Toni I; Guan, Yue; Horowitz, Carol R; Ramos, Michelle; Kimmel, Stephen E; McDonough, Caitrin W; Madden, Ebony B; Damschroder, Laura J

2018-06-01

PurposeImplementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing Genomics in Practice (IGNITE) Network's efforts to promote (i) a broader understanding of genomic medicine implementation research and (ii) the sharing of knowledge generated in the network.MethodsTo facilitate this goal, the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide its approach to identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross-network analyses.ResultsCMG identified 10 high-priority CFIR constructs as important for genomic medicine. Of those, eight did not have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model.ConclusionWe developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field.

Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs

PubMed Central

Simpatico, Thomas; Febo, Marcelo; Rodriquez, Chris; Dushaj, Kristina; Li, Mona; Braverman, Eric R.; Demetrovics, Zsolt; Oscar-Berman, Marlene; Badgaiyan, Rajendra D.

2016-01-01

The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli’s effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies. PMID:27246565

Systematic Review of Breastfeeding and Herbs

PubMed Central

Budzynska, Katarzyna; Gardner, Zoë E.; Dugoua, Jean-Jacques; Low Dog, Tieraona

2012-01-01

Abstract Objectives Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of this study was to systematically review the clinical literature on herbal medicine and lactation. Methods The databases PubMed, CAB Abstracts, Cochrane Central Register of Controlled Trials, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, and Reprotox were systematically searched for human trials from 1970 until 2010. Reference lists from relevant articles were hand-searched. Results Thirty-two studies met the inclusion criteria. Clinical studies were divided into three categories: survey studies (n=11), safety studies (n=8), and efficacy studies (n=13). Six studies were randomized controlled trials. The most common herbs studied were St. John's wort (Hypericum perforatum L.) (n=3), garlic (Allium sativum L.) extract (n=2), and senna (Cassia senna L.) (n=2). Studies were very heterogeneous with regard to study design, herbal intervention, and outcome measures. Overall, poor methodological quality predominated among the studies. Conclusions Our review concludes that further research is needed to assess the prevalence, efficacy, and safety of commonly used herbs during breastfeeding. PMID:22686865

Mitochondrial DNA mutations and cognition: a case-series report.

PubMed

Inczedy-Farkas, Gabriella; Trampush, Joey W; Perczel Forintos, Dora; Beech, Danielle; Andrejkovics, Monika; Varga, Zsofia; Remenyi, Viktoria; Bereznai, Benjamin; Gal, Aniko; Molnar, Maria Judit

2014-06-01

Mutations in the mitochondrial genome can impair normal metabolic function in the central nervous system (CNS) where cellular energy demand is high. Primary mitochondrial DNA (mtDNA) mutations have been linked to several mitochondrial disorders that have comorbid psychiatric, neurologic, and cognitive sequelae. Here, we present a series of cases with primary mtDNA mutations who were genotyped and evaluated across a common neuropsychological battery. Nineteen patients with mtDNA mutations were genotyped and clinically and cognitively evaluated. Pronounced deficits in nonverbal/visuoperceptual reasoning, verbal recall, semantic word generativity, and processing speed were evident and consistent with a "mitochondrial dementia" that has been posited. However, variation in cognitive performance was noteworthy, suggesting that the phenotypic landscape of cognition linked to primary mtDNA mutations is heterogeneous. Our patients with mtDNA mutations evidenced cognitive deficits quite similar to those commonly seen in Alzheimer's disease and could have clinical relevance to the evaluation of dementia. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The safety of pharmacologic treatment for pediatric obesity.

PubMed

Chao, Ariana M; Wadden, Thomas A; Berkowitz, Robert I

2018-04-01

Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above. Areas covered: This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed. Expert opinion: Orlistat, as an adjunct to lifestyle modification, results in modest weight losses and may be beneficial for some pediatric patients with obesity. However, gastrointestinal side effects are common and may limit use. In adults taking orlistat, rare but severe adverse events, including liver and renal events, have been reported. Recent pediatric pharmacokinetic studies of liraglutide have demonstrated similar safety and tolerability profiles as found in adults, with gastrointestinal disorders being the most common adverse events. Clinical trials are needed of liraglutide, as well as other medications for obesity, that systematically evaluate their risks and benefits in pediatric patients.

Status of vaccine research and development of vaccines for herpes simplex virus.

PubMed

Johnston, Christine; Gottlieb, Sami L; Wald, Anna

2016-06-03

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Self-medication for cough and the common cold: information needs of consumers.

PubMed

Kloosterboer, Sanne Maartje; McGuire, Treasure; Deckx, Laura; Moses, Geraldine; Verheij, Theo; van Driel, Mieke L

2015-07-01

Despite the high use of over-the-counter (OTC) cough and cold medicines, little is known about Australia's cough and cold medicines information needs. The aim of this study was to identify gaps in consumers' perceived knowledge and concerns, to better target consumer medicines information and improve quality use of medicines. We analysed cough-and-cold related enquiries from consumers who contacted an Australian national medicine call centre between September 2002 and June 2010. Of 5503 cough and cold calls, female callers made up 86% of the calls and 33% were related to children. Questions most frequently related to drug-drug interactions (29%). An analysis of narratives over an 18-month period (248 calls) revealed 20% of the calls concerned potentially clinically relevant interactions, particularly those involving psychotropic agents. The potential for interactions with cough and cold medicines purchased OTC is recognised by consumers. Patient information should address their concerns. Doctors should be aware of the common cough and cold interactions and communicate likely clinical symptoms to patients when prescribing medication to prevent potential harm.

DNA mutations of the cat: the good, the bad and the ugly.

PubMed

Lyons, Leslie A

2015-03-01

The health of the cat is a complex interaction between its environment (nurture) and its genetics (nature). Over 70 genetic mutations (variants) have been defined in the cat, many involving diseases, structural abnormalities and clinically relevant health concerns. As more of the cat's genome is deciphered, less commonly will the term 'idiopathic' be used regarding the diagnosis of diseases and unique health conditions. State-of-the-art health care will include DNA profiling of the individual cat, and perhaps its tumor, to establish the best treatment approaches. Genetic testing and eventually whole genome sequencing should become routine diagnostics for feline health care. Cat breeds have disseminated around the world. Thus, practitioners should be aware of the breeds common to their region and the mutations found in those regional populations. Specific random-bred populations can also have defined genetic characteristics and mutations. This review of 'the good, the bad and the ugly' DNA variants provides the current state of knowledge for genetic testing and genetic health management for cats. It is aimed at feline and general practitioners wanting to update and review the basics of genetics, what tests are available for cats and sources for genetic testing. The tables are intended to be used as references in the clinic. Practitioners with a high proportion of cat breeder clientele will especially benefit from the review. The data presented is extracted from peer-reviewed publications pertaining to mutation identification, and relevant articles concerning the heritable trait and/or disease. The author also draws upon personal experience and expertise in feline genetics. © ISFM and AAFP 2015.

Antibiotic Management of Lung Infections in Cystic Fibrosis. II. Nontuberculous Mycobacteria, Anaerobic Bacteria, and Fungi

PubMed Central

Aksamit, Timothy R.; Chotirmall, Sanjay H.; Dasenbrook, Elliott C.; Elborn, J. Stuart; LiPuma, John J.; Ranganathan, Sarath C.; Waters, Valerie J.; Ratjen, Felix A.

2014-01-01

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy. PMID:25167882

Understanding Bacterial Isolates in Blood Culture and Approaches Used to Define Bacteria as Contaminants: A Literature Review.

PubMed

Hossain, Belal; Islam, Mohammad Shahidul; Rahman, Atiqur; Marzan, Mahfuza; Rafiqullah, Iftekhar; Connor, Nicholas E; Hasanuzzaman, Mohammad; Islam, Maksuda; Hamer, Davidson H; Hibberd, Patricia L; Saha, Samir K

2016-05-01

Interpretation of blood culture isolates is challenging due to a lack of standard methodologies for identifying contaminants. This problem becomes more complex when the specimens are from sick young infants, as a wide range of bacteria can cause illness among this group. We used 43 key words to find articles published between 1970 and 2011 on blood culture isolates and possible contaminants in the PubMed database. Experts were also consulted to obtain other relevant articles. Selection of articles followed systematic methods considering opinions from more than 1 reviewer. After reviewing the titles of 3869 articles extracted from the database, we found 307 relevant to our objective. Based on the abstracts, 42 articles were selected for the literature review. In addition, we included 7 more articles based on cross-references and expert advice. The most common methods for differentiating blood culture isolates were multiple blood cultures from the same subject, antibiograms and molecular testing. Streptococcus pneumoniae, Hemophilus influenzae, Neisseria meningitidis and group A and B streptococcus were always considered as pathogens, whereas Bacillus sp., Diphtheroids, Propionibacterium and Micrococcus were commonly regarded as contaminants. Coagulase-negative staphylococci were the most frequent isolates and usually reported as contaminants unless the patient had a specific condition, such as long-term hospitalization or use of invasive devices (catheters). Inaccurate interpretation of blood culture may falsely guide treatment and also has long-term policy implications. The combination of clinical and microbiological knowledge, patient's clinical history and laboratory findings are essential for appropriate interpretation of blood culture.

Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

PubMed

Chmiel, James F; Aksamit, Timothy R; Chotirmall, Sanjay H; Dasenbrook, Elliott C; Elborn, J Stuart; LiPuma, John J; Ranganathan, Sarath C; Waters, Valerie J; Ratjen, Felix A

2014-10-01

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

Emerging souvenirs-clinical presentation of the returning traveller with imported arbovirus infections in Europe.

PubMed

Eckerle, I; Briciu, V T; Ergönül, Ö; Lupşe, M; Papa, A; Radulescu, A; Tsiodras, S; Tsitou, C; Drosten, C; Nussenblatt, V R; Reusken, C B; Sigfrid, L A; Beeching, N J

2018-03-01

Arboviruses are an emerging group of viruses that are causing increasing health concerns globally, including in Europe. Clinical presentation usually consists of a nonspecific febrile illness that may be accompanied by rash, arthralgia and arthritis, with or without neurological or haemorrhagic syndromes. The range of differential diagnoses of other infectious and noninfectious aetiologies is broad, presenting a challenge for physicians. While knowledge of the geographical distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the nonspecific and variable clinical presentation can delay final diagnosis. This narrative review aims to summarize the main clinical and laboratory-based findings of the three most common imported arboviruses in Europe. Evidence is extracted from published literature and clinical expertise of European arbovirus experts. We present three cases that highlight similarities and differences between some of the most common travel-related arboviruses imported to Europe. These include a patient with chikungunya virus infection presenting in Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus infection in Romania. Early diagnosis of travel-imported cases is important to reduce the risk of localized outbreaks of tropical arboviruses such as dengue and chikungunya and the risk of local transmission from body fluids or vertical transmission. Given the global relevance of arboviruses and the continuous risk of (re)emerging arbovirus events, clinicians should be aware of the clinical syndromes of arbovirus fevers and the potential pitfalls in diagnosis. Copyright © 2018. Published by Elsevier Ltd.

The registry case finding engine: an automated tool to identify cancer cases from unstructured, free-text pathology reports and clinical notes.

PubMed

Hanauer, David A; Miela, Gretchen; Chinnaiyan, Arul M; Chang, Alfred E; Blayney, Douglas W

2007-11-01

The American College of Surgeons mandates the maintenance of a cancer registry for hospitals seeking accreditation. At the University of Michigan Health System, more than 90% of all registry patients are identified by manual review, a method common to many institutions. We hypothesized that an automated computer system could accurately perform this time- and labor-intensive task. We created a tool to automatically scan free-text medical documents for terms relevant to cancer. We developed custom-made lists containing approximately 2,500 terms and phrases and 800 SNOMED codes. Text is processed by the Case Finding Engine (CaFE), and relevant terms are highlighted for review by a registrar and used to populate the registry database. We tested our system by comparing results from the CaFE to those by trained registrars who read through 2,200 pathology reports and marked relevant cases for the registry. The clinical documentation (eg, electronic chart notes) of an additional 476 patients was also reviewed by registrars and compared with the automated process by the CaFE. For pathology reports, the sensitivity for automated case identification was 100%, but specificity was 85.0%. For clinical documentation, sensitivity was 100% and specificity was 73.7%. Types of errors made by the CaFE were categorized to direct additional improvements. Use of the CaFE has resulted in a considerable increase in the number of cases added to the registry each month. The system has been well accepted by our registrars. CaFE can improve the accuracy and efficiency of tumor registry personnel and helps ensure that cancer cases are not overlooked.

Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

PubMed

Gillespie, Mary

2010-11-01

Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Clefting of the Alveolus: Emphasizing the Distinction from Cleft Palate.

PubMed

Wirtz, Nicholas; Sidman, James; Block, William

2016-05-01

Oral clefting is one of the most common significant fetal abnormalities. Cleft lip and cleft palate have drastically different clinical ramifications and management from one another. A cleft of the alveolus (with or without cleft lip) can confuse the diagnostic picture and lead to a false assumption of cleft palate. The cleft alveolus should be viewed on the spectrum of cleft lip rather than be associated with cleft palate. This is made evident by understanding the embryological development of the midface and relevant terminology. Cleft alveolus carries significantly different clinical implications and treatment options than that of cleft palate. Accurately distinguishing cleft alveolus from cleft palate is crucial for appropriate discussions regarding the patient's care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Lactose intolerance: from diagnosis to correct management.

PubMed

Di Rienzo, T; D'Angelo, G; D'Aversa, F; Campanale, M C; Cesario, V; Montalto, M; Gasbarrini, A; Ojetti, V

2013-01-01

This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance. The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management. Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity. Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test. Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy.

CURRENT CONCEPTS AND TREATMENT OF PATELLOFEMORAL COMPRESSIVE ISSUES.

PubMed

Mullaney, Michael J; Fukunaga, Takumi

2016-12-01

Patellofemoral disorders, commonly encountered in sports and orthopedic rehabilitation settings, may result from dysfunction in patellofemoral joint compression. Osseous and soft tissue factors, as well as the mechanical interaction of the two, contribute to increased patellofemoral compression and pain. Treatment of patellofemoral compressive issues is based on identification of contributory impairments. Use of reliable tests and measures is essential in detecting impairments in hip flexor, quadriceps, iliotibial band, hamstrings, and gastrocnemius flexibility, as well as in joint mobility, myofascial restrictions, and proximal muscle weakness. Once relevant impairments are identified, a combination of manual techniques, instrument-assisted methods, and therapeutic exercises are used to address the impairments and promote functional improvements. The purpose of this clinical commentary is to describe the clinical presentation, contributory considerations, and interventions to address patellofemoral joint compressive issues.

CURRENT CONCEPTS AND TREATMENT OF PATELLOFEMORAL COMPRESSIVE ISSUES

PubMed Central

Fukunaga, Takumi

2016-01-01

Patellofemoral disorders, commonly encountered in sports and orthopedic rehabilitation settings, may result from dysfunction in patellofemoral joint compression. Osseous and soft tissue factors, as well as the mechanical interaction of the two, contribute to increased patellofemoral compression and pain. Treatment of patellofemoral compressive issues is based on identification of contributory impairments. Use of reliable tests and measures is essential in detecting impairments in hip flexor, quadriceps, iliotibial band, hamstrings, and gastrocnemius flexibility, as well as in joint mobility, myofascial restrictions, and proximal muscle weakness. Once relevant impairments are identified, a combination of manual techniques, instrument-assisted methods, and therapeutic exercises are used to address the impairments and promote functional improvements. The purpose of this clinical commentary is to describe the clinical presentation, contributory considerations, and interventions to address patellofemoral joint compressive issues. PMID:27904792

Genetics and Genomics of Acute Neurologic Disorders.

PubMed

Maserati, Megan; Alexander, Sheila A

2018-01-01

Neurologic diseases and injuries are complex and multifactorial, making risk prediction, targeted treatment modalities, and outcome prognostication difficult and elusive. Genetics and genomics have affected clinical practice in many aspects in medicine, particularly cancer treatment. Advancements in knowledge of genetic and genomic variability in neurologic disease and injury are growing rapidly. Although these data are not yet ready for use in clinical practice, research continues to progress and elucidate information that eventually will provide answers to complex neurologic questions and serve as a platform to provide individualized care plans aimed at improving outcomes. This article provides a focused review of relevant literature on genetics, genomics, and common complex neurologic disease and injury likely to be seen in the acute care setting. ©2018 American Association of Critical-Care Nurses.

Expert consensus document: Advances in the evaluation of anorectal function.

PubMed

Carrington, Emma V; Scott, S Mark; Bharucha, Adil; Mion, François; Remes-Troche, Jose M; Malcolm, Allison; Heinrich, Henriette; Fox, Mark; Rao, Satish S

2018-05-01

Faecal incontinence and evacuation disorders are common, impair quality of life and incur substantial economic costs worldwide. As symptoms alone are poor predictors of underlying pathophysiology and aetiology, diagnostic tests of anorectal function could facilitate patient management in those cases that are refractory to conservative therapies. In the past decade, several major technological advances have improved our understanding of anorectal structure, coordination and sensorimotor function. This Consensus Statement provides the reader with an appraisal of the current indications, study performance characteristics, clinical utility, strengths and limitations of the most widely available tests of anorectal structure (ultrasonography and MRI) and function (anorectal manometry, neurophysiological investigations, rectal distension techniques and tests of evacuation, including defecography). Additionally, this article provides our consensus on the clinical relevance of these tests.

Bacterial Contamination During Diagnostic and Interventional Neuroangiography is a Frequent Finding: But Does It Matter? An Observational Study.

PubMed

Kabbasch, C; Dorn, F; Wenchel, H M; Krug, B; Mpotsaris, A; Liebig, T

2017-03-01

Bacterial contamination during angiographic procedures is a potential source of bacteremia. It is largely unknown whether it is clinically relevant. Our aim was to evaluate the incidence of contamination of liquids during catheter-based neuroangiographic examinations, the spectrum of microorganisms, a comparison of two different trolley-settings, and a follow-up of all patients with regard to clinical and lab signs of infection. A total of 170 patients underwent either diagnostic angiography (n = 111) or arterial neuroendovascular procedures (n = 59). To study the impact of airborne contamination of sterile liquids, we randomly assigned equal numbers of procedures to two distinct setups. Group A with standard open-surface bowls and group B with repetitive coverage of liquids throughout the procedure. Patient preparation was performed with utmost care. After each procedure, samples of the liquids were sent for microbiological evaluation. Patients were followed for signs of infection (fever, white blood cell count, C-reactive-protein). Of all samples, 25.3 % were contaminated. Contamination consisted of resident skin microbiota only and was more common with procedures (28.8 %) than with diagnostic angiography (23.4 %) and less common in uncovered (23.5 %) than in covered bowls (27.1 %). However, these differences were insignificant. None of the patients developed clinical or lab signs of infection. Contamination during diagnostic and interventional angiography does occur and cannot be avoided by intermittent coverage. Despite a surprisingly high incidence, our findings support the common strategy that antibiotic coverage is unnecessary in most patients undergoing arterial angiography as it lacks clinical impact. Airborne contamination does not appear to play a role.

Common data elements for substance use disorders in electronic health records: the NIDA Clinical Trials Network experience.

PubMed

Ghitza, Udi E; Gore-Langton, Robert E; Lindblad, Robert; Shide, David; Subramaniam, Geetha; Tai, Betty

2013-01-01

Electronic health records (EHRs) are essential in improving quality and enhancing efficiency of health-care delivery. By 2015, medical care receiving service reimbursement from US Centers for Medicare and Medicaid Services (CMS) must show 'meaningful use' of EHRs. Substance use disorders (SUD) are grossly under-detected and under-treated in current US medical care settings. Hence, an urgent need exists for improved identification of and clinical intervention for SUD in medical settings. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) has leveraged its infrastructure and expertise and brought relevant stakeholders together to develop consensus on brief screening and initial assessment tools for SUD in general medical settings, with the objective of incorporation into US EHRs. Stakeholders were identified and queried for input and consensus on validated screening and assessment for SUD in general medical settings to develop common data elements to serve as shared resources for EHRs on screening, brief intervention and referral to treatment (SBIRT), with the intent of supporting interoperability and data exchange in a developing Nationwide Health Information Network. Through consensus of input from stakeholders, a validated screening and brief assessment instrument, supported by Clinical Decision Support tools, was chosen to be used at out-patient general medical settings. The creation and adoption of a core set of validated common data elements and the inclusion of such consensus-based data elements for general medical settings will enable the integration of SUD treatment within mainstream health care, and support the adoption and 'meaningful use' of the US Office of the National Coordinator for Health Information Technology (ONC)-certified EHRs, as well as CMS reimbursement. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Ethical issues with informed consent from potential living kidney donors.

PubMed

Petrini, C

2010-05-01

Living organ donation and participation in clinical research trials have several features in common from an ethical perspective. The primary similarity is risk justification: the risk of harm to living organ donors and clinical research participants is justified by a resulting benefit to one or more other individuals. Some authors hold that organ donation and clinical trial participation are full-fledged duties. Such an implicit likening of the two leads to several considerations regarding informed consent in each situation. Informed consent raises ethical concerns in every medical context, and some of those concerns, such as competence, understanding, autonomy, and free or voluntary choice, are uniquely relevant to living organ donation and clinical trial participation. Most countries regulate informed consent procedures for living organ donation in great detail, and although informed consent procedures for clinical trial participation are somewhat less detailed, their rules are subject to review by ethics committees. It would be constructive for research participation informed consent procedures and living organ donation informed consent procedures to learn from one another. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

PubMed

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Systematic Review of Chinese Medicine for Miscarriage during Early Pregnancy

PubMed Central

Leung, Ping Chung; Chung, Tony Kwok Hung; Wang, Chi Chiu

2014-01-01

Background. Miscarriage is a very common complication during early pregnancy. So far, clinical therapies have limitation in preventing the early pregnancy loss. Chinese Medicine, regarded as gentle, effective, and safe, has become popular and common as a complementary and alternative treatment for miscarriages. However, the evidence to support its therapeutic efficacy and safety is still very limited. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and only few studies were selected for systematic review and conducted for meta-analysis. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, but potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in design, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more scientific evidences are still necessary to confirm the efficacy and safety of Chinese medicines during early pregnancy. PMID:24648851

Intensive care unit acquired weakness in children: Critical illness polyneuropathy and myopathy

PubMed Central

Kukreti, Vinay; Shamim, Mosharraf; Khilnani, Praveen

2014-01-01

Background and Aims: Intensive care unit acquired weakness (ICUAW) is a common occurrence in patients who are critically ill. It is most often due to critical illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is increasingly being recognized partly as a consequence of improved survival in patients with severe sepsis and multi-organ failure, partly related to commonly used agents such as steroids and muscle relaxants. There have been occasional reports of CIP and CIM in children, but little is known about their prevalence or clinical impact in the pediatric population. This review summarizes the current understanding of pathophysiology, clinical presentation, diagnosis and treatment of CIP and CIM in general with special reference to published literature in the pediatric age group. Subjects and Methods: Studies were identified through MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric studies were included. Results: ICUAW in children is a poorly described entity with unknown incidence, etiology and unclear long-term prognosis. Conclusions: Critical illness polyneuropathy and myopathy is relatively rare, but clinically significant sequelae of multifactorial origin affecting morbidity, length of intensive care unit (ICU) stay and possibly mortality in critically ill children admitted to pediatric ICU. PMID:24678152

Trustworthiness and relevance in web-based clinical question answering.

PubMed

Cruchet, Sarah; Boyer, Célia; van der Plas, Lonneke

2012-01-01

Question answering systems try to give precise answers to a user's question posed in natural language. It is of utmost importance that the answers returned are relevant to the user's question. For clinical QA, the trustworthiness of answers is another important issue. Limiting the document collection to certified websites helps to improve the trustworthiness of answers. On the other hand, limited document collections are known to harm the relevancy of answers. We show, however, in a comparative evaluation, that promoting trustworthiness has no negative effect on the relevance of the retrieved answers in our clinical QA system. On the contrary, the answers found are in general more relevant.

Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.

PubMed

Larkin, S E T; Johnston, H E; Jackson, T R; Jamieson, D G; Roumeliotis, T I; Mockridge, C I; Michael, A; Manousopoulou, A; Papachristou, E K; Brown, M D; Clarke, N W; Pandha, H; Aukim-Hastie, C L; Cragg, M S; Garbis, S D; Townsend, P A

2016-10-25

Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

Enhanced quality and quantity of retrieval of Critically Appraised Topics using the CAT Crawler.

PubMed

Dong, P; Mondry, A

2004-03-01

As healthcare moves towards the implementation of Evidence-Based Medicine (EBM), Critically Appraised Topics (CATs) become useful in helping physicians to make clinical decisions. A number of academic and healthcare organizations have set up web-based CAT libraries. The primary objective of the presented work is to provide a one-stop search and download site that allows access to multiple CAT libraries. A web-based application, namely the CAT Crawler, was developed to serve physicians with an adequate access to available appraised topics on the Internet. Important information is extracted automatically and regularly from CAT websites, and consolidated by checking the uniqueness and availability. The principle of meta-search is incorporated into the implementation of the search engine, which finds relevant topics following keyword input. The retrieved result directs the physician to the original resource page. A full-text article of a particular topic can be converted into a proper format for downloading to Personal Digital Assistant (PDA) devices. In summary, the application provides physicians with a common interface to retrieve relevant CATs on particular clinical topics from multiple resources, and thus speeds up the decision making process.

Biological monitoring of carcinogens: current status and perspectives.

PubMed

Pavanello, Sofia; Lotti, Marcello

2012-04-01

Biomonitoring exposures to carcinogens is common practice and a variety of biomarkers have been developed to assess both exposures and biochemical/biological effects. However, their clinical and preventive relevance is still uncertain. The understanding of cancer as a genetic disease has dramatically evolved during last decades, showing that cancer cell types acquire their characteristics with different strategies, time frames and microenvironments. Therefore, the place of current biomarkers within this complex scenario of gene-environment interactions leading to cancer cannot be defined. Reasons are manifold. Most studies assessed cancer risk on a group basis through snapshots taken at unknown time-points of the postulated chain of events. Little attention has been paid to the variety and variability of exposures, and no prospective study validated the indicators of biochemical/biological effects. New opportunities and suggestions for biomonitoring exposures to carcinogens could derive from exploring the exposome that combines exposures from all sources both external and internal. The discovery of new biomarkers and the identification of relevant gene-specific pathways could be achieved through metabolomic and genome-wide studies. In conclusion, it is possible to envisage personalized biomonitoring procedures, such as those already implemented in the context of nutrition and clinical oncology.

Red blood cell alloimmunization in transfused patients in sub-Saharan Africa: A systematic review and meta-analysis.

PubMed

Ngoma, Alain M; Mutombo, Paulin B; Ikeda, Kazuhiko; Nollet, Kenneth E; Natukunda, Bernard; Ohto, Hitoshi

2016-04-01

Previous studies of Sub-Saharan Africans show significant alloimmunization to red blood cell (RBC) antigens, but country-specific data are limited. Thus, the aim of this study was to estimate, by meta-analysis, the overall proportion of red blood cell alloantibodies among transfused patients. We systematically searched Medline, Embase, and the Africa-Wide Information database to identify relevant studies in any language. Case reports, comments, letters, conference abstracts, editorials, and review articles were excluded. Of the 269 potentially relevant articles, 11 studies fulfilled our selection criteria. Overall proportions of alloimmunization were 6.7 (95% CI: 5.7, 7.8) per 100 transfused patients. With regard to antibody specificity, among clinically significant antibodies, anti-E ranked as the most common, followed by anti-K, anti-C and anti-D. Meta-analysis of available literature quantifies and qualifies the clinical challenge of RBC alloimmunization among transfused patients in Sub-Saharan Africa. These results should drive policy decisions in favour of routine testing of RBC antigens and irregular antibodies for transfused patients as a standard of care throughout Sub-Saharan Africa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biology and Clinical Relevance of Acute Myeloid Leukemia Stem Cells.

PubMed

Reinisch, Andreas; Chan, Steven M; Thomas, Daniel; Majeti, Ravindra

2015-07-01

Evidence for the cancer stem cell model was first demonstrated in xenotransplanted blood and bone marrow samples from patients with acute myeloid leukemia (AML) almost two decades ago, supporting the concept that a rare clonal and mutated leukemic stem cell (LSC) population is sufficient to drive leukemic growth. The inability to eliminate LSCs with conventional therapies is thought to be the primary cause of disease relapse in AML patients, and as such, novel therapies with the ability to target this population are required to improve patient outcomes. An important step towards this goal is the identification of common immunophenotypic surface markers and biological properties that distinguish LSCs from normal hematopoietic stem and progenitor cells (HSPCs) across AML patients. This work has resulted in the development of a large number of potential LSC-selective therapies that target cell surface molecules, intracellular signaling pathways, and the bone marrow microenvironment. Here, we will review the basic biology, immunophenotypic detection, and clinical relevance of LSCs, as well as emerging biological and small-molecule strategies that either directly target LSCs or indirectly target these cells through modulation of their microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

Mental capacity to consent to treatment and the association with outcome: a longitudinal study in patients with anorexia nervosa

PubMed Central

Danner, Unna N.; Sternheim, Lot C.; McNeish, Daniel; Hoek, Hans W.; van Elburg, Annemarie A.

2017-01-01

Background Relevance of diminished mental capacity in anorexia nervosa (AN) to course of disorder is unknown. Aims To examine prognostic relevance of diminished mental capacity in AN. Method A longitudinal study was conducted in 70 adult female patients with severe AN. At baseline, mental capacity was assessed by psychiatrists, and clinical and neuropsychological data (decision-making) were collected. After 1 and 2 years, clinical and neuropsychological assessments were repeated, and remission and admission rates were calculated. Results People with AN with diminished mental capacity had a less favourable outcome with regard to remission and were admitted more frequently. Their appreciation of illness remained hampered. Decision-making did not improve, in contrast to people with full mental capacity. Conclusions People with AN with diminished mental capacity seem to do less well in treatment and display decision-making deficiencies that do not ameliorate with weight improvement. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28584660

Trainee participation is associated with adverse outcomes in emergency general surgery: an analysis of the National Surgical Quality Improvement Program database.

PubMed

Kasotakis, George; Lakha, Aliya; Sarkar, Beda; Kunitake, Hiroko; Kissane-Lee, Nicole; Dechert, Tracey; McAneny, David; Burke, Peter; Doherty, Gerard

2014-09-01

To identify whether resident involvement affects clinically relevant outcomes in emergency general surgery. Previous research has demonstrated a significant impact of trainee participation on outcomes in a broad surgical patient population. We identified 141,010 patients who underwent emergency general surgery procedures in the 2005-2010 Surgeons National Surgical Quality Improvement Program database. Because of the nonrandom assignment of complex cases to resident participation, patients were matched (1:1) on known risk factors [age, sex, inpatient status, preexisting comorbidities (obesity, diabetes, smoking, alcohol, steroid use, coronary artery disease, chronic renal failure, pulmonary disease)] and preoperatively calculated probability for morbidity and mortality. Clinically relevant outcomes were compared with a t or χ test. The impact of resident participation on outcomes was assessed with multivariable regression modeling, adjusting for risk factors and operative time. The most common procedures in the matched cohort (n = 83,790) were appendectomy (39.9%), exploratory laparotomy (8.8%), and adhesiolysis (6.6%). Trainee participation is independently associated with intra- and postoperative events, wound, pulmonary, and venous thromboembolic complications, and urinary tract infections. Trainee participation is associated with adverse outcomes in emergency general surgery procedures.

Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

PubMed Central

Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João

2017-01-01

Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.

PubMed

Friedrich, Torben; Rahmann, Sven; Weigel, Wilfried; Rabsch, Wolfgang; Fruth, Angelika; Ron, Eliora; Gunzer, Florian; Dandekar, Thomas; Hacker, Jörg; Müller, Tobias; Dobrindt, Ulrich

2010-10-21

The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.

Addressing unwarranted clinical variation: A rapid review of current evidence.

PubMed

Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

2018-05-15

Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and action are largely determined at a systems level currently, and stakeholder engagement in this process is limited. Lack of consensus on an evidence-based definition for UCV remains a substantial barrier to progress in this field. © 2018 John Wiley & Sons, Ltd.

The dynamics of HER2 status in esophageal adenocarcinoma

PubMed Central

Creemers, Aafke; Ebbing, Eva A.; Hooijer, Gerrit K.J.; Stap, Lisanne; Jibodh-Mulder, Rajni A.; Gisbertz, Susanne S.; van Berge Henegouwen, Mark I.; van Montfoort, Maurits L.; Hulshof, Maarten C.C.M.; Krishnadath, Kausilia K.; van Oijen, Martijn G.H.; Bijlsma, Maarten F.; Meijer, Sybren L.; van Laarhoven, Hanneke W.M.

2018-01-01

Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative. PMID:29928485

The dynamics of HER2 status in esophageal adenocarcinoma.

PubMed

Creemers, Aafke; Ebbing, Eva A; Hooijer, Gerrit K J; Stap, Lisanne; Jibodh-Mulder, Rajni A; Gisbertz, Susanne S; van Berge Henegouwen, Mark I; van Montfoort, Maurits L; Hulshof, Maarten C C M; Krishnadath, Kausilia K; van Oijen, Martijn G H; Bijlsma, Maarten F; Meijer, Sybren L; van Laarhoven, Hanneke W M

2018-06-01

Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen ( N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment ( N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% ( n = 3) and 3.3% ( n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% ( n = 2) of the resectable patients and 1.6% ( n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.

Development of a core outcome set for clinical trials in facial aging: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

PubMed

Schlessinger, Daniel I; Iyengar, Sanjana; Yanes, Arianna F; Henley, Jill K; Ashchyan, Hovik J; Kurta, Anastasia O; Patel, Payal M; Sheikh, Umar A; Franklin, Matthew J; Hanna, Courtney C; Chen, Brian R; Chiren, Sarah G; Schmitt, Jochen; Deckert, Stefanie; Furlan, Karina C; Poon, Emily; Maher, Ian A; Cartee, Todd V; Sobanko, Joseph F; Alam, Murad

2017-08-01

Facial aging is a concern for many patients. Wrinkles, loss of volume, and discoloration are common physical manifestations of aging skin. Genetic heritage, prior ultraviolet light exposure, and Fitzpatrick skin type may be associated with the rate and type of facial aging. Although many clinical trials assess the correlates of skin aging, there is heterogeneity in the outcomes assessed, which limits the quality of evaluation and comparison of treatment modalities. To address the inconsistency in outcomes, in this project we will develop a core set of outcomes that are to be evaluated in all clinical trials relevant to facial aging. A long list of measureable outcomes will be created from four sources: (1) systematic medical literature review, (2) patient interviews, (3) other published sources, and (4) stakeholder involvement. Two rounds of Delphi processes with homogeneous groups of physicians and patients will be performed to prioritize and condense the list. At a consensus meeting attended by physicians, patients, and stakeholders, outcomes will be further condensed on the basis of participant scores. By the end of the meeting, members will vote and decide on a final recommended set of core outcomes. Subsequent to this, specific measures will be selected or created to assess these outcomes. The aim of this study is to develop a core outcome set and relevant measures for clinical trials relevant to facial aging. We hope to improve the reliability and consistency of outcome reporting of skin aging, thereby enabling improved evaluation of treatment efficacy and patient satisfaction. Core Outcome Measures in Effectiveness Trials (COMET) Initiative, accessible at http://www.comet-initiative.org/studies/details/737 . Core Outcomes Set Initiative, (CSG-COUSIN) accessible at https://www.uniklinikum-dresden.de/de/das-klinikum/universitaetscentren/zegv/cousin/meet-the-teams/project-groups/core-outcome-set-for-the-appearance-of-facial-aging . Protocol version date is 28 July 2016.

Systematic reviews: guidance relevant for studies of older people.

PubMed

Shenkin, Susan D; Harrison, Jennifer K; Wilkinson, Tim; Dodds, Richard M; Ioannidis, John P A

2017-09-01

Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written-and if possible published-before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID)

PubMed Central

Hainsworth, Atticus H; Yeo, Natalie E; Weekman, Erica M; Wilcock, Donna M

2016-01-01

Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3–10µM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100–200µM), mild-moderate hyperhomocysteinemia ([HCy]: 10–100µM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100 µM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support Hcy as a mediator for VCID. In our view further trails of combined B-vitamin supplementation are called for, incorporating lessons from previous trails and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; target cohorts with low baseline B-vitamin status. PMID:26689889

Learning the preferences of physicians for the organization of result lists of medical evidence articles.

PubMed

O'Sullivan, D; Wilk, S; Michalowski, W; Slowinski, R; Thomas, R; Kadzinski, M; Farion, K

2014-01-01

Online medical knowledge repositories such as MEDLINE and The Cochrane Library are increasingly used by physicians to retrieve articles to aid with clinical decision making. The prevailing approach for organizing retrieved articles is in the form of a rank-ordered list, with the assumption that the higher an article is presented on a list, the more relevant it is. Despite this common list-based organization, it is seldom studied how physicians perceive the association between the relevance of articles and the order in which articles are presented. In this paper we describe a case study that captured physician preferences for 3-element lists of medical articles in order to learn how to organize medical knowledge for decision-making. Comprehensive relevance evaluations were developed to represent 3-element lists of hypothetical articles that may be retrieved from an online medical knowledge source such as MEDLINE or The Cochrane Library. Comprehensive relevance evaluations asses not only an article's relevance for a query, but also whether it has been placed on the correct list position. In other words an article may be relevant and correctly placed on a result list (e.g. the most relevant article appears first in the result list), an article may be relevant for a query but placed on an incorrect list position (e.g. the most relevant article appears second in a result list), or an article may be irrelevant for a query yet still appear in the result list. The relevance evaluations were presented to six senior physicians who were asked to express their preferences for an article's relevance and its position on a list by pairwise comparisons representing different combinations of 3-element lists. The elicited preferences were assessed using a novel GRIP (Generalized Regression with Intensities of Preference) method and represented as an additive value function. Value functions were derived for individual physicians as well as the group of physicians. The results show that physicians assign significant value to the 1st position on a list and they expect that the most relevant article is presented first. Whilst physicians still prefer obtaining a correctly placed article on position 2, they are also quite satisfied with misplaced relevant article. Low consideration of the 3rd position was uniformly confirmed. Our findings confirm the importance of placing the most relevant article on the 1st position on a list and the importance paid to position on a list significantly diminishes after the 2nd position. The derived value functions may be used by developers of clinical decision support applications to decide how best to organize medical knowledge for decision making and to create personalized evaluation measures that can augment typical measures used to evaluate information retrieval systems.

Metabonomics Research Progress on Liver Diseases.

PubMed

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

Periodontal Disease and Dental Caries among children and Adolescents Suffering from Endocrine Disorders - A Literature Review.

PubMed

Saminsky, Michael

2017-12-01

Dental caries and periodontal disease are the most common oral diseases. Their link to disorders of endocrine system is of high interest. Most of the available data relates to the adult population, though its importance among children and adolescents is paramount. To review the existing evidence examining the link between these clinical conditions among children and adolescents. Electronic bibliographic databases and hand searches of relevant publications, based on prepared list of relevant key-words was performed. Paucity of existing data leaves the question of association between most endocrine disorders of the youth with dental caries and periodontal disease, inconclusive, apart from obesity and diabetes mellitus, where it seems to be elucidated. A profound research should be done in order to amend our understanding to what extent, if at all, exists the link between these oral maladies and different pediatric endocrine disorders. Copyright© of YS Medical Media ltd.

Behavioral addictions: a novel challenge for psychopharmacology.

PubMed

Marazziti, Donatella; Presta, Silvio; Baroni, Stefano; Silvestri, Stefano; Dell'Osso, Liliana

2014-12-01

Although addictive syndromes have been traditionally related to substance-use disorders, during the last few decades a novel addictive group, including the so-called "behavioral or no-drug addictions," has been recognized and has attracted increasing attention for its relevant social impact. This group includes pathological gambling, compulsive shopping, TV/Internet/social network/videogame addictions, workaholism, sex and relationship addictions, orthorexia, and overtraining syndrome. Substance and behavioral addictions show similar phenomenological features, such as craving, dependence, tolerance, and abstinence, and perhaps they share a common possible pathophysiology. It is, however, controversial whether all or at least some of them should be considered real disorders or just normal, albeit extreme, behaviors. The aim of this article is to review current data on pharmacological treatment of behavioral addictions. As no specific and validated treatment algorithms are currently available, only an improved knowledge on their psychopathological, clinical, and neurobiological features may have relevant implications for more focused preventive and therapeutic strategies.

Development of an Electronic Medical Record-Based Clinical Decision Support Tool to Improve HIV Symptom Management

PubMed Central

Tsevat, Joel; Justice, Amy C.; Mrus, Joseph M.; Levin, Forrest; Kozal, Michael J.; Mattocks, Kristin; Farber, Steven; Rogers, Michelle; Erdos, Joseph; Brandt, Cynthia; Kudel, Ian; Braithwaite, Ronald

2009-01-01

Abstract Common symptoms associated with HIV disease and its management are often underrecognized and undertreated. A clinical decision support tool for symptom management was developed within the Veterans Health Administration electronic medical record (EMR), aiming at increasing provider awareness of and response to common HIV symptoms. Its feasibility was studied in March to May 2007 by implementing it within a weekly HIV clinic, comparing a 4-week intervention period with a 4-week control period. Fifty-six patients and their providers participated in the study. Patients' perceptions of providers' awareness of their symptoms, proportion of progress notes mentioning any symptom(s) and proportion of care plans mentioning any symptom(s) were measured. The clinical decision support tool used portable electronic “tablets” to elicit symptom information at the time of check-in, filtered, and organized that information into a concise and clinically relevant EMR note available at the point of care, and facilitated clinical responses to that information. It appeared to be well accepted by patients and providers and did not substantially impact workflow. Although this pilot study was not powered to detect effectiveness, 25 (93%) patients in the intervention group reported that their providers were very aware of their symptoms versuas 27 (75%) control patients (p = 0.07). The proportion of providers' notes listing symptoms was similar in both periods; however, there was a trend toward including a greater number of symptoms in intervention period progress notes. The symptom support tool seemed to be useful in clinical HIV care. The Veterans Health Administration EMR may be an effective “laboratory” for developing and testing decision supports. PMID:19538046

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

Applicability of randomized trials in radiation oncology to standard clinical practice.

PubMed

Apisarnthanarax, Smith; Swisher-McClure, Samuel; Chiu, Wing K; Kimple, Randall J; Harris, Stephen L; Morris, David E; Tepper, Joel E

2013-08-15

Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care. Copyright © 2013 American Cancer Society.

A conceptual framework for evaluating data suitability for observational studies.

PubMed

Shang, Ning; Weng, Chunhua; Hripcsak, George

2017-09-08

To contribute a conceptual framework for evaluating data suitability to satisfy the research needs of observational studies. Suitability considerations were derived from a systematic literature review on researchers' common data needs in observational studies and a scoping review on frequent clinical database design considerations, and were harmonized to construct a suitability conceptual framework using a bottom-up approach. The relationships among the suitability categories are explored from the perspective of 4 facets of data: intrinsic, contextual, representational, and accessible. A web-based national survey of domain experts was conducted to validate the framework. Data suitability for observational studies hinges on the following key categories: Explicitness of Policy and Data Governance, Relevance, Availability of Descriptive Metadata and Provenance Documentation, Usability, and Quality. We describe 16 measures and 33 sub-measures. The survey uncovered the relevance of all categories, with a 5-point Likert importance score of 3.9 ± 1.0 for Explicitness of Policy and Data Governance, 4.1 ± 1.0 for Relevance, 3.9 ± 0.9 for Availability of Descriptive Metadata and Provenance Documentation, 4.2 ± 1.0 for Usability, and 4.0 ± 0.9 for Quality. The suitability framework evaluates a clinical data source's fitness for research use. Its construction reflects both researchers' points of view and data custodians' design features. The feedback from domain experts rated Usability, Relevance, and Quality categories as the most important considerations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Dignity in end-of-life care: results of a national survey of US physicians

PubMed Central

Antiel, Ryan M.; Curlin, Farr A.; James, Katherine M.; Sulmasy, Daniel P.; Tilburt, Jon C.

2014-01-01

Context Debates persist about the relevance of “dignity” as an ethical concept in US healthcare, especially in end-of-life care. Objective To describe the attitudes and beliefs regarding the usefulness and meaning of the concept of dignity and to examine judgments about a clinical scenario in which dignity might be relevant. Methods 2000 practicing U.S. physicians, from all specialties, were mailed a survey. Main measures included physician’s judgments about an end-of-life clinical scenario (criterion variable), attitudes about the concept of dignity (predictors), and their religious characteristics (predictors). Results 1032 eligible physicians (54%) responded. Nine out of ten (90%) physicians reported that dignity was relevant to their practice. After controlling for age, gender, region, and specialty, physicians who judged that the case patient had either some dignity or full dignity, and who agreed that dignity is given by a creator, were all positively associated with believing that the patient’s life was worth living [OR 10.2 (5.8–17.8), OR 20.5 (11.4–36.8), OR 4.7 (3.1–7.0), respectively]. Respondents who strongly agreed that “all living humans have the same amount of dignity” were also more likely to believe that the patient’s life was worth living [OR 1.8 (1.2–2.7)]. Religious characteristics were also associated with believing that the case patient’s life was worth living [OR 4.1 (2.4–7.2), OR 3.2 (1.6–6.3), OR 9.2 (4.3–19.5), respectively]. Conclusion US physicians view the concept of dignity as useful. Those views are associated with their judgments about common end-of-life scenarios in which dignity concepts may be relevant. PMID:22762966

Commonalities and distinctions among mechanisms of addiction to alcohol and other drugs

PubMed Central

Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.

2015-01-01

Alcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. In this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in pre-clinical studies using rodent models of drug self-administration. While there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. For alcohol, versus other drugs of abuse, we discuss and compare advances in: 1) neurocircuitry important for the different stages of drug dependence; 2) transcriptomics and genetical genomics; and 3) enduring effects. We note in particular the contributions of behavioral genetics and animal models: discussions of progress specifically relevant to treatment development can be found in the accompanying review (Karoly et al, this issue). PMID:26431116

Reflections on relevance: Psychotherapy and Psychosomatics in 2004.

PubMed

Balon, Richard

2005-01-01

Relevance of an article is a highly desirable yet hardly predictable quality at the time of its publication. Article relevance is frequently measured by the impact factor of the journal where the article is published. Furthermore, impact factor, citation index and citation analysis are used as a measure of research progress and scientific wealth of a nation. The wisdom and significance of this approach to relevance is debatable and thus discussed here. In 2004, Psychotherapy and Psychosomatics published a variety of articles which, in the author's view, are clinically relevant. Several selected clinically relevant issues reviewed in this article include: the conceptualization of fibromyalgia as a stress disorder; the psychosocial impact and psychosocial interventions in cancer; the impact of alexithymia on patient care; the possible relationship between depression and nutrition (namely intake of folate and pyridoxal phosphate); the significance of hypercoagulability in panic-like anxiety; the questionable value of single isomer drugs, and the relevance and adequacy of clinimetrics versus psychometrics in clinical research. The reviewed issues seem to be relevant to clinical practice, research or both, but also to our critical thinking, and the critical review of the developments in psychiatry and psychology. Copyright 2005 S. Karger AG, Basel.

Occupational Contact Dermatitis in Mechanics and Repairers Referred for Patch Testing: Retrospective Analysis From the North American Contact Dermatitis Group 1998-2014.

PubMed

Warshaw, Erin M; Hagen, Solveig L; Sasseville, Denis; Maibach, Howard I; DeKoven, Joel G; Belsito, Donald V; Fowler, Joseph F; Zug, Kathryn A; Taylor, James S; Mathias, C G Toby; Fransway, Anthony F; DeLeo, Vincent A; Marks, James G; Pratt, Melanie D; Zirwas, Matthew J; Storrs, Frances J

Contact dermatoses are common in mechanic and repair occupations. This study aimed to (1) estimate the prevalence of occupationally related contact dermatitis among mechanics/repairers patch tested from 1998 to 2014 by the North American Contact Dermatitis Group, (2) characterize responsible allergens and irritants, and their sources, and (3) compare results among 3 occupational subgroups (mechanics, electrical/electronic, and other). A cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group between 1998 and 2014. Of 38,784 patients patch tested, 691 (1.8%) were mechanics/repairers. Male sex (93.5%) and hand involvement (59.5%) were common overall. Occupationally related skin disease was more prevalent among vehicle and mobile equipment mechanics/repairers (52.7%) and other mechanics/repairers (41.4%) than electrical/electronic equipment mechanics/repairers (21.3%). Overall, carba mix, thiuram mix, and methylchloroisothiazolone/methylisothiazolone were the most common occupation-related clinically relevant allergens. Gloves, automotive vehicles, solvents, oils, lubricants, and fuels were the most common sources of responsible allergens. Common occupationally related allergens included rubber accelerators and the preservative methylchloroisothiazolone/methylisothiazolone.

Spectrum of Celiac disease in Paediatric population: Experience of Tertiary Care Center from Pakistan.

PubMed

Aziz, Danish Abdul; Kahlid, Misha; Memon, Fozia; Sadiq, Kamran

2017-01-01

To determine clinical features and relevant laboratory investigations of patient with celiac disease (CD) and comparing classical celiac disease (CCD) with Non-diarrheal celiac disease (NDCD). This is a five years retrospective study conducted at The Aga Khan University Hospital Karachi, Pakistan from January 2010 to December 2015, enrolling children from one year to 15 years of either gender diagnosed as celiac disease in accordance with revised ESPGHAN criteria. Biopsy samples with grade 2 or more on Modified Marsh Classification were considered as consistent with celiac disease. Celiac patients were categorized into Classical celiac disease (with Chronic Diarrhea) and non-diarrheal celiac disease (Atypical celiac) and their clinical features and relevant laboratory investigations were documented. Total 66 patients were selected with celiac disease according to inclusion criteria, 39 (59.09%) patients were labeled as CCD and 27 (40.91%) patients were labeled as NDCD. Marsh grading 3a and above were more marked in CCD as compared to NDCD. Mean titer for Tissue transglutaminase antibodies (TTG) were higher in CCD group in comparison to NDCD group. In CCD, the most common clinical presentations were abdominal distension whereas in NDCD, the most remarkable features were recurrent abdominal pain (62.9%). Frequency of failure to thrive is significantly high in CCD (82.05%) but patients merely with short stature were more common in NDCD (33.3%). Refractory anemia was present in 66.6% patients in NDCD group and 41.1% patients in CCD group. 74.3% patients in CCD group were vitamin D deficient whereas 85% patient had vitamin D deficiency in NDCD group (p= 0.03). NDCD is not uncommon in our population. Recurrent abdominal pain, failure to thrive or patients only with short stature and refractory anemia are prominent features in NCDC group whereas abdominal distension, failure to thrive and recurrent abdominal pain were noticeable features in CCD. High grade histopathology and raised antibodies titer is hallmark of CCD. Vitamin D deficiency is almost equally present in both groups.

Antimicrobial activity of extracts from macroalgae Ulva lactuca against clinically important Staphylococci is impacted by lunar phase of macroalgae harvest.

PubMed

Deveau, A M; Miller-Hope, Z; Lloyd, E; Williams, B S; Bolduc, C; Meader, J M; Weiss, F; Burkholder, K M

2016-05-01

Staphylococcus aureus is a common human bacterial pathogen that causes skin and soft tissue infections. Methicillin-resistant Staph. aureus (MRSA) are increasingly drug-resistant, and thus there is great need for new therapeutics to treat Staph. aureus infections. Attention has focused on potential utility of natural products, such as extracts of marine macroalgae, as a source of novel antimicrobial compounds. The green macroalgae Ulva lactuca produces compounds inhibitory to human pathogens, although the effectiveness of U. lactuca extracts against clinically relevant strains of Staph. aureus is poorly understood. In addition, macroalgae produce secondary metabolites that may be influenced by exogenous factors including lunar phase, but whether lunar phase affects U. lactuca antimicrobial capacity is unknown. We sought to evaluate the antibacterial properties of U. lactuca extracts against medically important Staphylococci, and to determine the effect of lunar phase on antimicrobial activity. We report that U. lactuca methanolic extracts inhibit a range of Staphylococci, and that lunar phase of macrolagae harvest significantly impacts antimicrobial activity, suggesting that antimicrobial properties can be maximized by manipulating time of algal harvest. These findings provide useful parameters for future studies aimed at isolating and characterizing U. lactuca anti-Staphylococcal agents. The growing prevalence of antibiotic-resistant human pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) has intensified efforts towards discovery and development of novel therapeutics. Marine macroalgae like Ulva lactuca are increasingly recognized as potential sources of antimicrobials, but the efficacy of U. lactuca extracts against common, virulent strains of Staph. aureus is poorly understood. We demonstrate that U. lactuca methanolic extracts inhibit a variety of clinically relevant Staphylococcus strains, and that the antimicrobial activity can be maximized by optimizing time of algal harvest. These findings provide potentially useful parameters for future work of isolating and identifying novel antimicrobial agents from macroalgae. © 2016 The Society for Applied Microbiology.

Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.

PubMed

Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan

2016-12-01

Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues

PubMed Central

2011-01-01

Background As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics. Discussion This paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.' Summary Consideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility. PMID:21672210

Diagnostic value of clinical tests for degenerative rotator cuff disease in medical practice.

PubMed

Lasbleiz, S; Quintero, N; Ea, K; Petrover, D; Aout, M; Laredo, J D; Vicaut, E; Bardin, T; Orcel, P; Beaudreuil, J

2014-06-01

To assess the diagnostic value of clinical tests for degenerative rotator cuff disease (DRCD) in medical practice. Patients with DRCD were prospectively included. Eleven clinical tests of the rotator cuff have been done. One radiologist performed ultrasonography (US) of the shoulder. Results of US were expressed as normal tendon, tendinopathy or full-thickness tear (the reference). For each clinical test and each US criteria, sensitivity, specificity, negative predictive value and positive predictive value, accuracy, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were calculated. Clinical relevance was defined as PLR ≥2 and NLR ≤0.5. For 35 patients (39 shoulders), Jobe (PLR: 2.08, NLR: 0.31) and full-can (2, 0.5) test results were relevant for diagnosis of supraspinatus tears and resisted lateral rotation (2.42, 0.5) for infraspinatus tears, with weakness as response criteria. The lift-off test (8.50, 0.27) was relevant for subscapularis tears with lag sign as response criteria. Yergason's test (3.7, 0.41) was relevant for tendinopathy of the long head of the biceps with pain as a response criterion. There was no relevant clinical test for diagnosis of tendinopathy of supraspinatus, infraspinatus or subscapularis. Five of 11 clinical tests were relevant for degenerative rotator cuff disease. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Paracoccidioidomycosis of the mouth: an emerging deep mycosis.

PubMed

Almeida, Oslei Paes; Jorge Junior, Jacks; Scully, Crispian

2003-01-01

Oral fungal infections (mycoses) have come into particular prominence since the advent of infection with Human Immunodeficiency Virus (HIV), and recognition of the Acquired Immune Deficiency Syndrome (AIDS), as well as the phenomenal increase in world travel with increased exposure to infections endemic in the tropics. Paracoccidioidomycosis is a rare mycosis worldwide but common in Brazil and some other areas in Latin America. It can be life-threatening and can manifest with a spectrum of clinical presentations, including frequent oral lesions. This paper reviews the more recent information on Paracoccidioidomycosis, emphasizing those areas most relevant in dental science.

Lactate biosensors: current status and outlook.

PubMed

Rassaei, Liza; Olthuis, Wouter; Tsujimura, Seiya; Sudhölter, Ernst J R; van den Berg, Albert

2014-01-01

Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors for direct applications. In this review, we provide an overview of the most immediate and relevant developments toward this end, and we discuss and assess common transduction approaches. Further, we critically describe the pros and cons of current commercial lactate sensors and envision how future sensing design may benefit from emerging new technologies.

Osteoporosis in Inflammatory Bowel Disease

PubMed Central

Ali, Tauseef; Lam, David; Bronze, Michael S.; Humphrey, Mary Beth

2010-01-01

Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner. PMID:19559158

Clindamycin phosphate-tretinoin combination gel revisited: status report on a specific formulation used for acne treatment.

PubMed

Del Rosso, James Q

2017-03-01

Topical agents, including retinoids and antibiotics, are commonly used to treat acne vulgaris (AV) and remain as components of acne treatment guidelines. Approved topical combination formulations offer the advantages of established efficacy, decreased frequency of application, and improved convenience for patients. This article discusses both clindamycin phosphate (CP) and tretinoin (Tret) as components of a topical aqueous-based combination gel that has been shown to be effective, safe, and well tolerated for treatment of facial AV. Clinically relevant considerations with use of this treatment are also discussed, including therapeutic advantages and potential limitations.

[Classification of enuresis/encopresis according to DSM-5].

PubMed

von Gontard, Alexander

2014-03-01

Elimination disorders are common in childhood and adolescence. Enuresis is traditionally defined as wetting from the age of 5 years and encopresis as soiling from 4 years onwards - after all organic causes have been excluded. In the past decades, many subtypes of elimination disorders have been identified with different symptoms, etiologies, and specific treatment options. Unfortunately, the DSM-5 criteria did not integrate these new approaches. In contrast, classification systems of the International Children's Incontinence Society (ICCS) for enuresis and urinary incontinence as well as the ROME-III criteria for fecal incontinence offer new and relevant suggestions for both clinical and research purposes.

National athletic trainers' association position statement: skin diseases.

PubMed

Zinder, Steven M; Basler, Rodney S W; Foley, Jack; Scarlata, Chris; Vasily, David B

2010-01-01

To present recommendations for the prevention, education, and management of skin infections in athletes. Trauma, environmental factors, and infectious agents act together to continually attack the integrity of the skin. Close quarters combined with general poor hygiene practices make athletes particularly vulnerable to contracting skin diseases. An understanding of basic prophylactic measures, clinical features, and swift management of common skin diseases is essential for certified athletic trainers to aid in preventing the spread of infectious agents. These guidelines are intended to provide relevant information on skin infections and to give specific recommendations for certified athletic trainers and others participating in athletic health care.

Herb-drug interaction: a case study of effect of ginger on the pharmacokinetic of metronidazole in rabbit.

PubMed

Okonta, J M; Uboh, M; Obonga, W O

2008-01-01

The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole (P<0.05). Thus, in clinical practice, the patients should be advised on the serious implication of using both items together.

Trauma Patient with Fat Embolism Detected on Computed Tomography.

PubMed

Sousa, Isabel; Janeiro, João; Campos, Paula; Távora, Isabel

2017-01-31

Fat embolism is frequent following fractures of long bones, however the development of the clinical syndrome of fat embolism (characterized by progressive respiratory distress, mental status depression and petechial rash) is rare, but relevant because of its potential severity. We report a case of a trauma patient with multiple fractures of the right lower limb in whom an emergency computed tomography scan showed fat emboli within the lumen of the homolateral common femoral vein. The imaging detection of macroscopic fat emboli should alert the clinician to the potential for subsequent fat embolism syndrome.

[Current study and research progress of whiplash injury of cervical vertebrae].

PubMed

Guo, Ying; Jia, Lian-shun

2011-07-01

Whiplash injury is a common injures in our daily lives, but the mechanism of it and the best treatment is largely unknown. The development of chronic pain and disability following whiplash injury is not uncommon and results in substantial social and economic costs. Clinical manifestation and recovery time are difference, which make it difficult for doctor diagnosis and treatment. The current study have shown that the social class, severity of collision, compensation and lawsuit, physical and psychological factors were relevant predictors for the outcome of whiplash. This article is try to overview the status quo of the whiplash injury.

Evidence-Based Advances in Avian Medicine.

PubMed

Summa, Noémie M; Guzman, David Sanchez-Migallon

2017-09-01

This article presents relevant advances in avian medicine and surgery over the past 5 years. New information has been published to improve clinical diagnosis in avian diseases. This article also describes new pharmacokinetic studies. Advances in the understanding and treatment of common avian disorders are presented in this article, as well. Although important progress has been made over the past years, there is still much research that needs to be done regarding the etiology, pathophysiology, diagnosis, and treatment of avian diseases and evidence-based information is still sparse in the literature. Copyright © 2017 Elsevier Inc. All rights reserved.

Thinking beyond the Common Candida Species: Need for Species-Level Identification of Candida Due to the Emergence of Multidrug-Resistant Candida auris.

PubMed

Lockhart, Shawn R; Jackson, Brendan R; Vallabhaneni, Snigdha; Ostrosky-Zeichner, Luis; Pappas, Peter G; Chiller, Tom

2017-12-01

Candida species are one of the leading causes of nosocomial infections. Because much of the treatment for Candida infections is empirical, some institutions do not identify Candida to species level. With the worldwide emergence of the multidrug-resistant species Candida auris , identification of Candida to species level has new clinical relevance. Species should be identified for invasive candidiasis isolates, and species-level identification can be considered for selected noninvasive isolates to improve detection of C. auris . Copyright © 2017 American Society for Microbiology.

Case study of first episode schizophrenia in pregnancy and postpartum.

PubMed

Kast, Kristopher A; Agarkar, Smita

2017-08-01

Patients with first-episode psychosis of peripartum onset commonly prove to have a mood-disorder diathesis; however, a proportion of cases represent first-episode schizophrenia. We present such a case and discuss the clinical relevance of recognizing this small but important population of new mothers. These patients are at considerable risk of misdiagnosis, resulting in ineffective maintenance therapy, poorer recovery of function, and development of treatment resistance. Accurate diagnosis in the peripartum period will impact treatment decisions and long-term therapy. Clinicians need to be vigilant, especially during maintenance therapy, to identify these patients and ensure appropriate antipsychotic therapy is provided.

Diagnosis and Management of Behavioral Variant Frontotemporal Dementia

PubMed Central

Pressman, Peter; Miller, Bruce L

2014-01-01

Frontotemporal dementia (FTD) was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that may be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes may further diagnosis, treatment and research. PMID:24315411

Nanomedicine – challenge and perspectives

PubMed Central

Riehemann, Kristina; Schneider, Stefan W.; Luger, Thomas A.; Godin, Biana; Ferrari, Mauro; Fuchs, Harald

2014-01-01

Nanomedicine introduces nanotechnology concepts into medicine and thus joins two large cross disciplinary fields with an unprecedented societal and economical potential arising from the natural combination of specific achievements in the respective fields. The common basis evolves from the molecular scale properties relevant in the two fields. Nanoanalytical tools such as local probes and molecular imaging techniques, allow us to characterize surface and interface properties at a nanometer scale at predefined locations, while elaborated chemical approaches offer the opportunity for the control and addressing of surfaces e. g. for targeted drug delivery, enhanced biocompatibility and neuroprosthetic purposes. This commonality opens a wide variety of economic fields both of industrial and clinical interests. However, concerns arise in this cross disciplinary area about toxicological aspects and ethical implications. This review gives an overview of selected recent developments of nanotechnology applied on medical objectives. PMID:19142939

Cardiovascular risk in Turner syndrome.

PubMed

Donato, Beatriz; Ferreira, Maria João

2018-06-01

Turner syndrome is a relatively common genetic disorder of female development, characterized by partial or complete absence of an X chromosome, with a variable clinical presentation. Congenital or acquired cardiovascular disease is highly prevalent and a major cause of early death in this syndrome. The most feared complication is aortic dissection, which can occur at a very young age and requires careful assessment of its risk factors. A systematic literature search identified sixty relevant publications. These were reviewed with regard to the increased risk of cardiovascular disease in women with Turner syndrome, especially in pregnancy. The most common congenital cardiovascular defects are presented and illustrated with appropriate iconography. The current recommendations regarding the screening and monitoring of cardiovascular disease in these patients are discussed. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Retrieval of diagnostic and treatment studies for clinical use through PubMed and PubMed's Clinical Queries filters.

PubMed

Lokker, Cynthia; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Walter, Stephen D

2011-01-01

Clinical Queries filters were developed to improve the retrieval of high-quality studies in searches on clinical matters. The study objective was to determine the yield of relevant citations and physician satisfaction while searching for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with searching PubMed without these filters. Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction. For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance. Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions. Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

Clinical relevance of diagnosing COPD by fixed ratio or lower limit of normal: a systematic review.

PubMed

van Dijk, Wouter D; Gupta, Nisha; Tan, Wan C; Bourbeau, Jean

2014-02-01

Different spirometric criteria in diagnosing COPD have been advocated by different groups, debilitating adequate diagnosis and treatment of COPD. We reviewed the clinical relevance of fixed ratio and lower limit of normal (LLN) in diagnosing COPD and explored if modifying factors may affect their clinical relevance. Two reviewers independently searched PubMed and Embase for papers that compared both criteria on any clinically relevant outcome, published before June 1st, 2012, without any language restriction. Two reviewers independently extracted the study characteristics, including study design, population characteristics and diagnostic criteria used, and summarized the results of clinical relevance. Study quality was assessed by scoring forms for bias and level of evidence. Of 394 studies retrieved, 11 studies were included, with a median of 1,258 participants. Although both criteria appeared related with various clinically relevant outcomes, we were unable to prefer one criterion over the other, with various performances of the criteria for different outcomes. Should the criteria disagree on diagnosis, an alternative diagnosis should be suspected, in particular in those (elderly) with less severe airflow limitation for whom the LLN appears a better criterion. The fixed ratio appears to perform better in subjects with more severe airflow limitation. In diagnosing COPD, severity of airflow limitation appears an important factor for choosing whether the fixed ratio or LLN. Disagreement between the criteria is suggestive for an alternative diagnosis. Future studies on clinical relevance should further reveal the criterion of choice, in order to improve adequate diagnosis and consequent treatments.

Effects of intranasal xylometazoline, alone or in combination with ipratropium, in patients with common cold.

PubMed

Eccles, Ronald; Martensson, Kaj; Chen, Shirley C

2010-04-01

Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10-26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (<10 days). No clinically important differences in ciliary motility and mucociliary clearance were observed. Xylometazoline does not result in sympathomimetic systemic side effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine). The few studies available in common cold suggest that intranasal xylometazoline provides fast and effective relief of nasal congestion and is well tolerated. When xylometazoline is used in combination with ipratropium, patients with common cold experience the additive benefit of nasal congestion and rhinorrhoea being treated simultaneously.

Fragrance allergy in patients with hand eczema - a clinical study.

PubMed

Heydorn, Siri; Johansen, Jeanne Duus; Andersen, Klaus E; Bruze, Magnus; Svedman, Cecilia; White, Ian R; Basketter, David A; Menné, Torkil

2003-06-01

Fragrance allergy and hand eczema are both common among dermatological patients. Fragrance mix (FM) and its constituents have a recognized relevance to exposure to fine fragrances and cosmetic products. Based on extensive chemical analysis and database search, a new selection of fragrances was established, including 14 known fragrance allergens present in products to which hand exposure would occur. A non-irritating patch-test concentration for some fragrances was established in 212 consecutive patients. 658 consecutive patients presenting with hand eczema were patch tested with the European standard series and the developed selection of fragrances. 67 (10.2%) of the 658 patients had a positive reaction to 1 or more of our selection of fragrance chemicals present in the new selection. The most common reactions to fragrances not included in the FM were to citral, Lyral (hydroxyisohexyl-3-cyclohexene carboxaldehyde) and oxidized l-limonene. A concomitant reaction to the FM identified potential fragrance allergy in less than (1/2) of these patients. Exposure assessment and a statistically significant association between a positive patch test to our selected fragrances and patients' history support the relevance of this selection of fragrances. Those with a positive reaction to our selected fragrances were significantly more likely to have 1 or more positive patch tests in the standard series. This observation is the basis for the hypothesis concerning cross-reactivity and the effect of simultaneous exposure. The study found that fragrance allergy could be a common problem in patients with eczema on the hands.

Methicillin-resistant Staphylococcus aureus: an overview for manual therapists().

PubMed

Green, Bart N; Johnson, Claire D; Egan, Jonathon Todd; Rosenthal, Michael; Griffith, Erin A; Evans, Marion Willard

2012-03-01

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with difficult-to-treat infections and high levels of morbidity. Manual practitioners work in environments where MRSA is a common acquired infection. The purpose of this review is to provide a practical overview of MRSA as it applies to the manual therapy professions (eg, physical and occupational therapy, athletic training, chiropractic, osteopathy, massage, sports medicine) and to discuss how to identify and prevent MRSA infections in manual therapy work environments. PubMed and CINAHL were searched from the beginning of their respective indexing years through June 2011 using the search terms MRSA, methicillin-resistant Staphylococcus aureus, and Staphylococcus aureus. Texts and authoritative Web sites were also reviewed. Pertinent articles from the authors' libraries were included if they were not already identified in the literature search. Articles were included if they were applicable to ambulatory health care environments in which manual therapists work or if the content of the article related to the clinical management of MRSA. Following information extraction, 95 citations were included in this review, to include 76 peer-reviewed journal articles, 16 government Web sites, and 3 textbooks. Information was organized into 10 clinically relevant categories for presentation. Information was organized into the following clinically relevant categories: microbiology, development of MRSA, risk factors for infection, clinical presentation, diagnostic tests, screening tests, reporting, treatment, prevention for patients and athletes, and prevention for health care workers. Methicillin-resistant S aureus is a health risk in the community and to patients and athletes treated by manual therapists. Manual practitioners can play an essential role in recognizing MRSA infections and helping to control its transmission in the health care environment and the community. Essential methods for protecting patients and health care workers include being aware of presenting signs, patient education, and using appropriate hand and clinic hygiene.

The Clinical Neuroscience Course: Viewing Mental Health from Neurobiological Perspectives

PubMed Central

Lambert, Kelly G.

2005-01-01

Although the field of neuroscience is booming, a challenge for researchers in mental health disciplines is the integration of basic research findings into applied clinical approaches leading to effective therapies. Recently the National Institute of Mental Health called for translational research grants to encourage collaboration between neuroscientists and mental health professionals. In order for this “clinical neuroscience” to emerge and thrive, an important first step is the provision of appropriate course offerings so that future neuroscience researchers and mental health practitioners will have a common neurobiological base from which to make informed decisions about the most efficacious treatments for mental illnesses. Accordingly, an integrative course, Clinical Neuroscience, was developed to address these issues. After reviewing the historical origins of this emerging discipline, students are exposed to fundamental overviews of neuroanatomy, neurochemistry, and neural development before approaching the neurobiological components of several disorders (e.g., schizophrenia, depression, Tourette’s syndrome, drug abuse, obsessive compulsive disorder). Finally, the maintenance of mental health is emphasized as topics such as psychoneuroimmunology, coping with stress, and eating regulation are discussed. Important themes emphasized in this course include (1) the consideration of only empirically based evidence, (2) the view that mental illness represents a disruption of neurobiological homeostasis, (3) the acknowledgement that, because the brain is a plastic organ, the clinical relevance of environmental and behavioral influences is difficult to overestimate, and (4) the recognition of the value of ecologically relevant animal models in the investigation of various aspects of mental illness. Because of the importance of stress maintenance in mental health, exercises have been developed to increase students’ awareness of their own coping strategies. Finally, several books and movies are incorporated to provide additional points of view of the topics discussed in the course. PMID:23494100

GP leadership in clinical commissioning groups: a qualitative multi-case study approach across England.

PubMed

Marshall, Martin; Holti, Richard; Hartley, Jean; Matharu, Tatum; Storey, John

2018-06-01

Clinical commissioning groups (CCGs) were established in England in 2013 to encourage GPs to exert greater influence over the processes of service improvement and redesign in the NHS. Little is known about the extent and the ways in which GPs have assumed these leadership roles. To explore the nature of clinical leadership of GPs in CCGs, and to examine the enablers and barriers to implementing a policy of clinical leadership in the NHS. A qualitative multi-case study approach in six localities across England. The case studies were purposefully sampled to represent different geographical localities and population demographics, and for their commitment to redesigning specified clinical or service areas. Data were collected from the case study CCGs and their partner organisations using a review of relevant documents, semi-structured individual or group interviews, and observations of key meetings. The data were analysed thematically and informed by relevant theories. GPs prefer a collaborative style of leadership that may be unlikely to produce rapid or radical change. Leadership activities are required at all levels in the system from strategy to frontline delivery, and the leadership behaviours of GPs who are not titular leaders are as important as formal leadership roles. A new alliance is emerging between clinicians and managers that draws on their different skillsets and creates new common interests. The uncertain policy environment in the English NHS is impacting on the willingness and the focus of GP leaders. GPs are making an important contribution as leaders of health service improvement and redesign but there are significant professional and political barriers to them optimising a leadership role. © British Journal of General Practice 2018.

An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

PubMed

Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

2010-01-01

BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

Optimizing biologically targeted clinical trials for neurofibromatosis

PubMed Central

Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

2014-01-01

Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

Cryopreservation and Revival of Human Mesenchymal Stromal Cells.

PubMed

Haack-Sørensen, Mandana; Ekblond, Annette; Kastrup, Jens

2016-01-01

Cell-based therapy is a promising and innovative new treatment for different degenerative and autoimmune diseases, and mesenchymal stromal cells (MSCs) from the bone marrow have demonstrated great therapeutic potential due to their immunosuppressive and regenerative capacities.The establishment of methods for large-scale expansion of clinical-grade MSCs in vitro has paved the way for their therapeutic use in clinical trials. However, the clinical application of MSCs also requires cryopreservation and banking of the cell products. To preserve autologous or allogeneic MSCs for future clinical applications, a reliable and effective cryopreservation method is required.Developing a successful cryopreservation protocol for clinical stem cell products, cryopreservation media, cryoprotectant agents (CPAs), the freezing container, the freezing temperature, and the cooling and warming rate are all aspects which should be considered.A major challenge is the selection of a suitable cryoprotectant which is able to penetrate the cells and yet has low toxicity.This chapter focuses on recent technological developments relevant for the cryopreservation of MSCs using the most commonly used cryopreservation medium containing DMSO and animal serum or human-derived products for research use and the animal protein-free cryopreservation media CryoStor (BioLife Solutions) for clinical use.

Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population

PubMed Central

Glans, Martin; Humble, Mats B.

2017-01-01

Background Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. Aims To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. Method Hakim-Grahame’s 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population (n=1039). Results In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. Conclusions Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28959454

Insights from clinical research completed during the west Africa Ebola virus disease epidemic

PubMed Central

Rojek, Amanda; Horby, Peter; Dunning, Jake

2018-01-01

The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

Clinical next-generation sequencing in patients with non-small cell lung cancer.

PubMed

Hagemann, Ian S; Devarakonda, Siddhartha; Lockwood, Christina M; Spencer, David H; Guebert, Kalin; Bredemeyer, Andrew J; Al-Kateb, Hussam; Nguyen, TuDung T; Duncavage, Eric J; Cottrell, Catherine E; Kulkarni, Shashikant; Nagarajan, Rakesh; Seibert, Karen; Baggstrom, Maria; Waqar, Saiama N; Pfeifer, John D; Morgensztern, Daniel; Govindan, Ramaswamy

2015-02-15

A clinical assay was implemented to perform next-generation sequencing (NGS) of genes commonly mutated in multiple cancer types. This report describes the feasibility and diagnostic yield of this assay in 381 consecutive patients with non-small cell lung cancer (NSCLC). Clinical targeted sequencing of 23 genes was performed with DNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue. The assay used Agilent SureSelect hybrid capture followed by Illumina HiSeq 2000, MiSeq, or HiSeq 2500 sequencing in a College of American Pathologists-accredited, Clinical Laboratory Improvement Amendments-certified laboratory. Single-nucleotide variants and insertion/deletion events were reported. This assay was performed before methods were developed to detect rearrangements by NGS. Two hundred nine of all requisitioned samples (55%) were successfully sequenced. The most common reason for not performing the sequencing was an insufficient quantity of tissue available in the blocks (29%). Excisional, endoscopic, and core biopsy specimens were sufficient for testing in 95%, 66%, and 40% of the cases, respectively. The median turnaround time (TAT) in the pathology laboratory was 21 days, and there was a trend of an improved TAT with more rapid sequencing platforms. Sequencing yielded a mean coverage of 1318×. Potentially actionable mutations (ie, predictive or prognostic) were identified in 46% of 209 samples and were most commonly found in KRAS (28%), epidermal growth factor receptor (14%), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (4%), phosphatase and tensin homolog (1%), and BRAF (1%). Five percent of the samples had multiple actionable mutations. A targeted therapy was instituted on the basis of NGS in 11% of the sequenced patients or in 6% of all patients. NGS-based diagnostics are feasible in NSCLC and provide clinically relevant information from readily available FFPE tissue. The sample type is associated with the probability of successful testing. © 2014 American Cancer Society.

Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007.

PubMed

Forshey, Brett M; Guevara, Carolina; Laguna-Torres, V Alberto; Cespedes, Manuel; Vargas, Jorge; Gianella, Alberto; Vallejo, Efrain; Madrid, César; Aguayo, Nicolas; Gotuzzo, Eduardo; Suarez, Victor; Morales, Ana Maria; Beingolea, Luis; Reyes, Nora; Perez, Juan; Negrete, Monica; Rocha, Claudio; Morrison, Amy C; Russell, Kevin L; Blair, Patrick J; Olson, James G; Kochel, Tadeusz J

2010-08-10

Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology.

Diagnosis and Inflammatory Response of Patients with Candiduria

PubMed Central

Helbig, S.; Achkar, J. M.; Jain, N.; Wang, X.; Gialanella, P.; Levi, M; Fries, B.C.

2012-01-01

Summary Background Candiduria is common in hospitalized patients but the clinical relevance is still unclear. Objective This study was done to further our knowledge on detection of and host responses to candiduria. Patients Urines and clinical data from 136 patients in whom presence of yeast was diagnosed by microscopic urinalysis were collected. Diagnosis by standard urine culture methods on blood and MacConkey agar as well as on fungal culture medium (Sabouraud dextrose agar) was compared. Inflammatory parameters (IL-6 and IL-17, Ig) were quantified in the urine and compared to levels in control patients without candiduria. Results and Conclusions Standard urine culture methods detected only 37% of Candida spp. in urine. Sensitivity was especially low (23%) for C. glabrata and was independent of fungal burden. Candida specific IgG but not IgA was significantly elevated when compared to control patients (p<0.0001 and 0.07, respectively). In addition, urine levels of IL-6 and IL-17 were significantly higher in candiduric patients when compared to control patients (p<0.001). Multivariate analysis documented an independent association between an increased IgG (odds ratio (OR) 136.0, 95% confidence interval (CI) 25.7 to 719.2; p<0.0001), an increased IL-17 (OR 17.4, 95% CI 5.3–57.0; p<0.0001) and an increased IL-6 level (OR 4.9, 95% CI 1.9–12.4; p=0.001) and candiduria. In summary, our data indicate that clinical studies on candiduria should include fungal urine culture and that inflammatory parameters may be helpful to identify patients with clinically relevant candiduria. PMID:22574854

Do the Trajectories of Bipolar Disorder and Schizophrenia Follow a Universal Staging Model?

PubMed

Duffy, Anne; Malhi, Gin S; Grof, Paul

2017-02-01

The purpose of this study is to address the question of whether a universal staging model of severe psychiatric disorders is a viable direction for future research by examining the extant literature. A narrative review was conducted of the relevant historical, conceptual, and empirical literature pertaining to the clinical trajectory of bipolar disorder and schizophrenia and issues relevant to staging. There is substantive evidence that classic recurrent bipolar disorder is separable from schizophrenia on the basis of family history, developmental and clinical course, treatment response, and neurobiological findings. However, because of the intrinsic heterogeneity of diagnostic categories that has been amplified by recent changes in psychiatric taxonomy, key distinctions between the groups have become obfuscated. While mapping risk and illness markers to emerging psychopathology is a logical approach and may be of value for some psychiatric disorders and/or their clinical subtypes, robust evidence supporting identifiable stages per se is still lacking. Presently, even rudimentary stages such as prodromes cannot be meaningfully applied across different disorders and no commonalities can be found for the basis of universal staging. Advances in the prediction of risk, accurate early illness detection, and tailored intervention will require mapping biomarkers and other risk indicators to reliable clinical phases of illness progression. Given the capricious nature of mood and psychotic disorders, this task is likely to yield success only if conducted in narrowly defined subgroups of individuals at high risk for specific illnesses. This approach is diametrically opposite to that being promulgated by proponents of a universal staging model.

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

PubMed

Heffler, Enrico; Sberna, Maria Eva; Sichili, Stefania; Intravaia, Rossella; Nicolosi, Giuliana; Porto, Morena; Liuzzo, Maria Teresa; Picardi, Giuseppe; Fichera, Silvia; Crimi, Nunzio

2016-02-01

Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. Copyright © 2016. Published by Elsevier Inc.

Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?

PubMed

Mouly, Stéphane; Lloret-Linares, Célia; Sellier, Pierre-Olivier; Sene, Damien; Bergmann, J-F

2017-04-01

An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reforming medical education in ethics and humanities by finding common ground with Abraham Flexner.

PubMed

Doukas, David J; McCullough, Laurence B; Wear, Stephen

2010-02-01

Abraham Flexner was commissioned by the Carnegie Foundation for the Advancement of Teaching to conduct the 1910 survey of all U.S. and Canadian medical schools because medical education was perceived to lack rigor and strong learning environments. Existing proprietary schools were shown to have inadequate student scholarship and substandard faculty and teaching venues. Flexner's efforts and those of the American Medical Association resulted in scores of inadequate medical schools being closed and the curricula of the survivors being radically changed. Flexner presumed that medical students would already be schooled in the humanities in college. He viewed the humanities as essential to physician development but did not explicitly incorporate this position into his 1910 report, although he emphasized this point in later writings. Medical ethics and humanities education since 1970 has sought integration with the sciences in medical school. Most programs, however, are not well integrated with the scientific/clinical curriculum, comprehensive across four years of training, or cohesive with nationally formulated goals and objectives. The authors propose a reformation of medical humanities teaching in medical schools inspired by Flexner's writings on premedical education in the context of contemporary educational requirements. College and university education in the humanities is committed to a broad education, consistent with long-standing tenets of liberal arts education. As a consequence, premedical students do not study clinically oriented science or humanities. The medical school curriculum already provides teaching of clinically relevant sciences. The proposed four-year curriculum should likewise provide clinically relevant humanities teaching to train medical students and residents comprehensively in humane, professional patient care.

Non-obvious correlations to disease management unraveled by Bayesian artificial intelligence analyses of CMS data.

PubMed

Vemulapalli, Vijetha; Qu, Jiaqi; Garren, Jeonifer M; Rodrigues, Leonardo O; Kiebish, Michael A; Sarangarajan, Rangaprasad; Narain, Niven R; Akmaev, Viatcheslav R

2016-11-01

Given the availability of extensive digitized healthcare data from medical records, claims and prescription information, it is now possible to use hypothesis-free, data-driven approaches to mine medical databases for novel insight. The goal of this analysis was to demonstrate the use of artificial intelligence based methods such as Bayesian networks to open up opportunities for creation of new knowledge in management of chronic conditions. Hospital level Medicare claims data containing discharge numbers for most common diagnoses were analyzed in a hypothesis-free manner using Bayesian networks learning methodology. While many interactions identified between discharge rates of diagnoses using this data set are supported by current medical knowledge, a novel interaction linking asthma and renal failure was discovered. This interaction is non-obvious and had not been looked at by the research and clinical communities in epidemiological or clinical data. A plausible pharmacological explanation of this link is proposed together with a verification of the risk significance by conventional statistical analysis. Potential clinical and molecular pathways defining the relationship between commonly used asthma medications and renal disease are discussed. The study underscores the need for further epidemiological research to validate this novel hypothesis. Validation will lead to advancement in clinical treatment of asthma & bronchitis, thereby, improving patient outcomes and leading to long term cost savings. In summary, this study demonstrates that application of advanced artificial intelligence methods in healthcare has the potential to enhance the quality of care by discovering non-obvious, clinically relevant relationships and enabling timely care intervention. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Factors associated to clinical learning in nursing students in primary health care: an analytical cross-sectional study

PubMed Central

Serrano-Gallardo, Pilar; Martínez-Marcos, Mercedes; Espejo-Matorrales, Flora; Arakawa, Tiemi; Magnabosco, Gabriela Tavares; Pinto, Ione Carvalho

2016-01-01

ABSTRACT Objective: to identify the students' perception about the quality of clinical placements and asses the influence of the different tutoring processes in clinical learning. Methods: analytical cross-sectional study on second and third year nursing students (n=122) about clinical learning in primary health care. The Clinical Placement Evaluation Tool and a synthetic index of attitudes and skills were computed to give scores to the clinical learning (scale 0-10). Univariate, bivariate and multivariate (multiple linear regression) analyses were performed. Results: the response rate was 91.8%. The most commonly identified tutoring process was "preceptor-professor" (45.2%). The clinical placement was assessed as "optimal" by 55.1%, relationship with team-preceptor was considered good by 80.4% of the cases and the average grade for clinical learning was 7.89. The multiple linear regression model with more explanatory capacity included the variables "Academic year" (beta coefficient = 1.042 for third-year students), "Primary Health Care Area (PHC)" (beta coefficient = 0.308 for Area B) and "Clinical placement perception" (beta coefficient = - 0.204 for a suboptimal perception). Conclusions: timeframe within the academic program, location and clinical placement perception were associated with students' clinical learning. Students' perceptions of setting quality were positive and a good team-preceptor relationship is a matter of relevance. PMID:27627124

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

The ASEAN economic community and medical qualification

PubMed Central

Kittrakulrat, Jathurong; Jongjatuporn, Witthawin; Jurjai, Ravipol; Jarupanich, Nicha; Pongpirul, Krit

2014-01-01

Background In the regional movement toward ASEAN Economic Community (AEC), medical professions including physicians can be qualified to practice medicine in another country. Ensuring comparable, excellent medical qualification systems is crucial but the availability and analysis of relevant information has been lacking. Objective This study had the following aims: 1) to comparatively analyze information on Medical Licensing Examinations (MLE) across ASEAN countries and 2) to assess stakeholders’ view on potential consequences of AEC on the medical profession from a Thai perspective. Design To search for relevant information on MLE, we started with each country's national body as the primary data source. In case of lack of available data, secondary data sources including official websites of medical universities, colleagues in international and national medical student organizations, and some other appropriate Internet sources were used. Feasibility and concerns about validity and reliability of these sources were discussed among investigators. Experts in the region invited through HealthSpace.Asia conducted the final data validation. For the second objective, in-depth interviews were conducted with 13 Thai stakeholders, purposely selected based on a maximum variation sampling technique to represent the points of view of the medical licensing authority, the medical profession, ethicists and economists. Results MLE systems exist in all ASEAN countries except Brunei, but vary greatly. Although the majority has a national MLE system, Singapore, Indonesia, and Vietnam accept results of MLE conducted at universities. Thailand adopted the USA's 3-step approach that aims to check pre-clinical knowledge, clinical knowledge, and clinical skills. Most countries, however, require only one step. A multiple choice question (MCQ) is the most commonly used method of assessment; a modified essay question (MEQ) is the next most common. Although both tests assess candidate's knowledge, the Objective Structured Clinical Examination (OSCE) is used to verify clinical skills of the examinee. The validity of the medical license and that it reflects a consistent and high standard of medical knowledge is a sensitive issue because of potentially unfair movement of physicians and an embedded sense of domination, at least from a Thai perspective. Conclusions MLE systems differ across ASEAN countries in some important aspects that might be of concern from a fairness viewpoint and therefore should be addressed in the movement toward AEC. PMID:25215908

The selective determination of sulfates, sulfonates, and phosphates in urine by capillary electrophoresis/mass spectrometry.

PubMed

Bunz, Svenja-Catharina; Neusüß, Christian

2013-01-01

Metabolite identification and metabolite profiling are of major importance in the pharmaceutical and clinical context. However, anions of biological relevance such as sulfates, sulfonates, and phosphates are rarely included in common techniques for metabolite studies. In this protocol, we demonstrate a unique method to selectively determine these anions. The method comprises a capillary electrophoresis separation using an acidic background electrolyte (pH ≤ 2) and anodic detection by mass spectrometry via negative electrospray ionization. In this way, only anions of strong acids like sulfates are determined. The selectivity for sulfur-containing species is proved based on the specific isotopic ratios. In conjunction with the accurate mass from the time-of-flight mass spectrometer, the presented method is well suited for clinical and pharmaceutical applications to identify possible metabolites and to quantify known metabolites.

The Effects of Aging on Clinical Vestibular Evaluations

PubMed Central

Maheu, Maxime; Houde, Marie-Soleil; Landry, Simon P.; Champoux, François

2015-01-01

Balance disorders are common issues for aging populations due to the effects of normal aging on peripheral vestibular structures. These changes affect the results of vestibular function evaluations and make the interpretation of these results more difficult. The objective of this article is to review the current state of knowledge of clinically relevant vestibular measures. We will first focus on otolith function assessment methods cervical-VEMP (cVEMP) and ocular-VEMP (oVEMP), then the caloric and video-head impulse test (vHIT) methods for semicircular canals assessment. cVEMP and oVEMP are useful methods, though research on the effects of age for some parameters are still inconclusive. vHIT results are largely independent of age as compared to caloric stimulation and should therefore be preferred for the evaluation of the semicircular canals function. PMID:26441824

Practical approach to the gastrointestinal manifestations of cystic fibrosis.

PubMed

Bolia, Rishi; Ooi, Chee Y; Lewindon, Peter; Bishop, Jonathan; Ranganathan, Sarath; Harrison, Jo; Ford, Kristyn; van der Haak, Natalie; Oliver, Mark R

2018-05-16

Cystic fibrosis (CF) is the most common, life-shortening, genetic illness affecting children in Australia and New Zealand. The genetic abnormality results in abnormal anion transport across the apical membrane of epithelial cells in a number of organs, including the lungs, gastrointestinal tract, liver and genito-urinary tract. Thus, CF is a multi-system disorder that requires a multi-disciplinary approach. Respiratory disease is the predominant cause of both morbidity and mortality in patients with CF. However, there are significant and clinically relevant gastrointestinal, liver, pancreatic and nutritional manifestations that must be detected and managed in a timely and structured manner. The aim of this review is to provide evidence-based information and clinical algorithms to guide the nutritional and gastrointestinal management of patients with CF. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

[Advances in the research of mechanism in prevention and treatment of scar with botulinum toxin type A and its clinical application].

PubMed

Li, Y H; Liu, J Q; Xiao, D; Zhang, W; Hu, D H

2017-04-20

Scar is a common complication in wound healing process, and how to effectively prevent and treat it is a hot and difficult problem in burns and plastic surgery field. Botulinum toxin type A is a neurotoxin that has been widely and effectively used in the cosmetic surgery field such as anti-wrinkle and thin face. In recent years, botulinum toxin type A has been applied in prevention and treatment of scar, which causes a great concern. Nowadays, the relevant reports have gradually increased, and the mechanisms have been explored more deeply. This article aims to summarize the possible mechanisms and clinical reports on the prevention and treatment of scar by botulinum toxin type A to provide a new way for the prevention and treatment of scar after surgery.

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group.

PubMed

Wickwire, Emerson M; Williams, Scott G; Roth, Thomas; Capaldi, Vincent F; Jaffe, Michael; Moline, Margaret; Motamedi, Gholam K; Morgan, Gregory W; Mysliwiec, Vincent; Germain, Anne; Pazdan, Renee M; Ferziger, Reuven; Balkin, Thomas J; MacDonald, Margaret E; Macek, Thomas A; Yochelson, Michael R; Scharf, Steven M; Lettieri, Christopher J

2016-04-01

Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

The potential for stem cells in cerebral palsy--piecing together the puzzle.

PubMed

Faulkner, Stuart D; Ruff, Crystal A; Fehlings, Michael G

2013-06-01

The substantial socioeconomic burden of a diagnosis of cerebral palsy, coupled with a positive anecdotal and media spin on stem cell treatments, drives many affected families to seek information and treatment outside of the current clinical and scientific realm. Preclinical studies using several types of stem and adult cells--including mesenchymal stem cells, neural precursor cells, olfactory ensheathing glia and Schwann cells--have demonstrated some regenerative and functional efficacy in neurologic paradigms. This paper describes the most common cell types investigated for transplant in vivo and summarizes the current state of early-phase clinical trials. It investigates the most relevant and promising coadministered therapies, including rehabilitation, drug targeting, magnetic stimulation, and bioengineering approaches. We highlight the need for adjunctive combinatorial strategies to successfully transfer stem cell treatments from bench to bedside. Copyright © 2013 Elsevier Inc. All rights reserved.

Application of Immunohistochemistry and Molecular Diagnostics to Clinically Relevant Problems in Endometrial Cancer Bojana Djordjevic, Shannon Westin, Russell R. Broaddus

PubMed Central

Djordjevic, Bojana; Westin, Shannon; Broaddus, Russell R.

2012-01-01

Synopsis A number of different clinical scenarios are presented in which lab-based analyses beyond the usual diagnosis based on light microscopic examination of H&E stained slides – immunohistochemistry and PCR-based assays such as sequencing, mutation testing, microsatellite instability analysis, and determination of MLH1 methylation - are most helpful for guiding diagnosis and treatment of endometrial cancer. The central goal of this information is to provide a practical guide of key current and emerging issues in diagnostic endometrial cancer pathology that require the use of ancillary laboratory techniques, such as immunohistochemistry and molecular testing. The authors present the common diagnostic problems in endometrial carcinoma pathology, types of endometrial carcinoma, description of tissue testing and markers, pathological features, and targeted therapy. PMID:23687522

Retention of knowledge and perceived relevance of basic sciences in an integrated case-based learning (CBL) curriculum

PubMed Central

2013-01-01

Background Knowledge and understanding of basic biomedical sciences remain essential to medical practice, particularly when faced with the continual advancement of diagnostic and therapeutic modalities. Evidence suggests, however, that retention tends to atrophy across the span of an average medical course and into the early postgraduate years, as preoccupation with clinical medicine predominates. We postulated that perceived relevance demonstrated through applicability to clinical situations may assist in retention of basic science knowledge. Methods To test this hypothesis in our own medical student cohort, we administered a paper-based 50 MCQ assessment to a sample of students from Years 2 through 5. Covariates pertaining to demographics, prior educational experience, and the perceived clinical relevance of each question were also collected. Results A total of 232 students (Years 2–5, response rate 50%) undertook the assessment task. This sample had comparable demographic and performance characteristics to the whole medical school cohort. In general, discipline-specific and overall scores were better for students in the latter years of the course compared to those in Year 2; male students and domestic students tended to perform better than their respective counterparts in certain disciplines. In the clinical years, perceived clinical relevance was significantly and positively correlated with item performance. Conclusions This study suggests that perceived clinical relevance is a contributing factor to the retention of basic science knowledge and behoves curriculum planners to make clinical relevance a more explicit component of applied science teaching throughout the medical course. PMID:24099045

Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

NASA Astrophysics Data System (ADS)

Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

2014-03-01

Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report.

PubMed

Malesker, Mark A; Callahan-Lyon, Priscilla; Ireland, Belinda; Irwin, Richard S

2017-11-01

Acute cough associated with the common cold (CACC) causes significant impairment in quality of life. Effective treatment approaches are needed for CACC. We conducted a systematic review on the management of CACC to update the recommendations and suggestions of the CHEST 2006 guideline on this topic. This systematic review of randomized controlled trials (RCTs) asked the question: Is there evidence of clinically relevant treatment effects for pharmacologic or nonpharmacologic therapies in reducing the duration/severity of acute CACC? Studies of adults and pediatric patients with CACC were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on using the American College of Chest Physicians organization methodology. Six systematic reviews and four primary studies identified from updated literature searches for each of the reviews or from hand searching were included and reported data on 6,496 participants with CACC who received one or more of a variety of interventions. The studies used an assortment of descriptors and assessments to identify CACC. The evidence supporting the management of CACC is overall of low quality. This document provides treatment suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Genetics, gene expression and bioinformatics of the pituitary gland.

PubMed

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2009-04-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. Copyright 2009 S. Karger AG, Basel.

Hand-arm vibration syndrome: What family physicians should know.

PubMed

Shen, Shixin Cindy; House, Ronald A

2017-03-01

To provide family physicians with an understanding of the epidemiology, pathogenesis, symptoms, diagnosis, and management of hand-arm vibration syndrome (HAVS), an important and common occupational disease in Canada. A MEDLINE search was conducted for research and review articles on HAVS. A Google search was conducted to obtain gray literature relevant to the Canadian context. Additional references were obtained from the articles identified. Hand-arm vibration syndrome is a prevalent occupational disease affecting workers in multiple industries in which vibrating tools are used. However, it is underdiagnosed in Canada. It has 3 components-vascular, in the form of secondary Raynaud phenomenon; sensorineural; and musculoskeletal. Hand-arm vibration syndrome in its more advanced stages contributes to substantial disability and poor quality of life. Its diagnosis requires careful history taking, in particular occupational history, physical examination, laboratory tests to rule out alternative diagnoses, and referral to an occupational medicine specialist for additional investigations. Management involves reduction of vibration exposure, avoidance of cold conditions, smoking cessation, and medication. To ensure timely diagnosis of HAVS and improve prognosis and quality of life, family physicians should be aware of this common occupational disease and be able to elicit the relevant occupational history, refer patients to occupational medicine clinics, and appropriately initiate compensation claims. Copyright© the College of Family Physicians of Canada.

Artificial intelligence, physiological genomics, and precision medicine.

PubMed

Williams, Anna Marie; Liu, Yong; Regner, Kevin R; Jotterand, Fabrice; Liu, Pengyuan; Liang, Mingyu

2018-04-01

Big data are a major driver in the development of precision medicine. Efficient analysis methods are needed to transform big data into clinically-actionable knowledge. To accomplish this, many researchers are turning toward machine learning (ML), an approach of artificial intelligence (AI) that utilizes modern algorithms to give computers the ability to learn. Much of the effort to advance ML for precision medicine has been focused on the development and implementation of algorithms and the generation of ever larger quantities of genomic sequence data and electronic health records. However, relevance and accuracy of the data are as important as quantity of data in the advancement of ML for precision medicine. For common diseases, physiological genomic readouts in disease-applicable tissues may be an effective surrogate to measure the effect of genetic and environmental factors and their interactions that underlie disease development and progression. Disease-applicable tissue may be difficult to obtain, but there are important exceptions such as kidney needle biopsy specimens. As AI continues to advance, new analytical approaches, including those that go beyond data correlation, need to be developed and ethical issues of AI need to be addressed. Physiological genomic readouts in disease-relevant tissues, combined with advanced AI, can be a powerful approach for precision medicine for common diseases.

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

PubMed Central

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W.; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P.; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2011-01-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. PMID:19407506

Detecting clinically relevant new information in clinical notes across specialties and settings.

PubMed

Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

2017-07-05

Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

Depressive symptoms and depression in people screened positive for dementia in primary care - results of the DelpHi-study.

PubMed

Thyrian, Jochen René; Eichler, Tilly; Reimann, Melanie; Wucherer, Diana; Dreier, Adina; Michalowsky, Bernhard; Hoffmann, Wolfgang

2016-06-01

Dementia and depression are common syndromes in the elderly. There is lack of knowledge concerning the frequency of depressive symptoms in people with dementia (PWD) and factors associated with depression. The aim of this analysis is to (a) describe the frequency of depressive symptoms in people screened positive for dementia, (b) describe differences between PWD with and without depressive symptoms, and (c) analyze associations between depressive symptoms and other dementia-related variables. Analyses are based on data of the GP-based intervention trial DelpHi-MV. A sample of 430 (6.29%) people screened positive for dementia in primary care was analyzed regarding depression according to the German version of the Geriatric Depression Scale (GDS, 15-items), demographic variables, and dementia/depression-related variables. Multivariate analyses were conducted to identify factors associated with depressive symptoms. The mean GDS-score of depressive symptoms in n = 430 PWD was m = 3.21 (SD 2.45) with 67 PWD (15.55%) showing clinically relevant depression (GDS < 5) m = 7.71 (SD = 1.92). A total of n = 72 (16.74%) received a formal diagnosis of depression and n = 62 (14.42%) received antidepressive drug treatment. Depressive symptoms are significantly associated with age (OR = 0.93), functional impairment (OR = 1.36), and quality of life (OR = 0.01, CI: 0.00-0.06). Our results support previous findings that clinically relevant depressive symptoms are more common in people screened positive for dementia than in the general population and are often missed or mismanaged. Our findings underline the importance of managing quality of life, functional status, or depressive symptoms. Also, the results highlight the benefit of including the partner (and probably other carers) for adequate treatment of PWD.

Statistical significance versus clinical relevance.

PubMed

van Rijn, Marieke H C; Bech, Anneke; Bouyer, Jean; van den Brand, Jan A J G

2017-04-01

In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus, and Related Disorders: A Way Forward

PubMed Central

Kurlan, Roger; Leckman, James

2010-01-01

Abstract Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas—the basal ganglia of the brain and the related cortical and thalamic sites—adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. PMID:20807070

Review of existing experimental approaches for the clinical evaluation of the benefits of plant food supplements on cardiovascular function.

PubMed

Meoni, Paolo; Restani, Patrizia; Mancama, Dalu T

2013-06-01

We conducted a survey of the National Centre for Biotechnology Information (NCBI) PubMed database to identify methods most commonly used for the evaluation of the effect of plant food supplements on the cardiovascular system and their relevance to the regulatory status of these products. Particularly, our search strategy was aimed at the selection of studies concerning the clinical evaluation of the beneficial effects of the most commonly studied plant food supplements acting on the cardiovascular system. Following the screening of 3839 papers for inclusion criteria, 48 published reports were retained for this review. Most studies included in this review used a double blind controlled design, and evaluated the effect of plant food supplements on individuals affected by a disease of the cardiovascular system. The majority of the studies were found to be of low methodological quality on the Jadad scale, mainly because of inadequate reporting of adverse events and of patient withdrawals. In comparison, measures used for the evaluation of benefits included mostly cardiovascular risk factors as recommended in international guidelines and in accordance with principles laid down for the evaluation of health claims in food. The risk factors most frequently evaluated belonged to the category of "lipid function and levels", "heart function" and "blood pressure". For the absolute majority of the studies, the study period did not exceed one month. This review highlights critical factors to be considered in the design of studies evaluating the health effects of plant food supplements on the cardiovascular system. Between others, the inclusion of healthy individuals, better reporting and description of the characteristics of the product used could improve the quality and relevance of these studies.

Barosinusitis: Comprehensive review and proposed new classification system

PubMed Central

Vaezeafshar, Reza; Psaltis, Alkis J.; Rao, Vidya K.; Zarabanda, David; Patel, Zara M.

2017-01-01

Background: Barosinusitis, or sinus barotrauma, may arise from changes in ambient pressure that are not compensated by force equalization mechanisms within the paranasal sinuses. Barosinusitis is most commonly seen with barometric changes during flight or diving. Understanding and better classifying the pathophysiology, clinical presentation, and management of barosinusitis are essential to improve patient care. Objectives: To perform a comprehensive review of the available literature regarding sinus barotrauma. Methods: A comprehensive literature search that used the terms “barosinusitis,” “sinus barotrauma,” and “aerosinusitis” was conducted, and all identified titles were reviewed for relevance to the upper airway and paranasal sinuses. All case reports, series, and review articles that were identified from this search were included. Selected cases of sinus barotrauma from our institution were included to illustrate classic signs and symptoms. Results: Fifty-one articles were identified as specifically relevant to, or referencing, barosinusitis and were incorporated into this review. The majority of articles focused on barosinusitis in the context of a single specific etiology rather than independent of etiology. From analysis of all the publications combined with clinical experience, we proposed that barosinusitis seemed to fall within three distinct subtypes: (1) acute, isolated barosinusitis; (2) recurrent acute barosinusitis; and (3) chronic barosinusitis. We introduced this terminology and suggested independent treatment recommendations for each subtype. Conclusion: Barosinusitis is a common but potentially overlooked condition that is primed by shifts in the ambient pressure within the paranasal sinuses. The pathophysiology of barosinusitis has disparate causes, which likely contribute to its misdiagnosis and underdiagnosis. Available literature compelled our proposed modifications to existing classification schemes, which may allow for improved awareness and management strategies for barosinusitis. PMID:29070267

Physical Performance Measures of Flexibility, Hip Strength, Lower Limb Power and Trunk Endurance in Healthy Navy Cadets: Normative Data and Differences Between Sex and Limb Dominance.

PubMed

Lopes, Thiago Jambo Alves; Simic, Milena; Alves, Daniel de Souza; Bunn, Priscila Dos Santos; Rodrigues, Allan Inoue; Terra, Bruno de Souza; Lima, Maicom da Silva; Ribeiro, Fabrício Miranda; Vilão, Patrick; Pappas, Evangelos

2018-01-17

The objectives were to provide normative data on commonly used physical performance tests that may be associated with musculoskeletal injuries in Navy cadets, and assess for sex and limb dominance differences. A large cohort of Navy cadets were assessed for physical performance tests of flexibility (ankle dorsiflexion range of motion and sit and reach), isometric hip strength, lower limb power (single leg hop), and trunk endurance (plank and side plank tests). Besides providing normative data tables, sex and limb dominance differences were assessed by a two-way mixed ANOVA. A total of 545 Brazilian Navy cadets (394 males) representing 79% of the cadets in the Academy participated. Normative reference values were reported as mean±SD, 95%CI and percentiles. For tests of muscle strength, power and endurance, males performed better than females (p<0.001). For flexibility tests, females achieved greater distances than males for the sit and reach test (p<0.001), but no difference for ankle dorsiflexion (p=0.51). Overall, there were no clinically relevant differences between limbs. In conclusion, normative data for commonly used physical performance tests were provided. Although no clinically relevant side-to-side differences were found, males presented higher values for lower limb strength and power, as well as trunk endurance than females, while females demonstrated increased flexibility. Valuable normative data are provided to professionals who work with young, active populations from the injury prevention or rehabilitation perspective; as the current study may help professionals to identify athletes or cadets whose performance is outside the normative values and may be at risk for injury.

Controlled study on enteropathogens in travellers returning from the tropics with and without diarrhoea.

PubMed

Paschke, C; Apelt, N; Fleischmann, E; Perona, P; Walentiny, C; Löscher, T; Herbinger, K-H

2011-08-01

Diarrhoea is the most frequent health problem among travellers in the tropics. However, data on the spectrum and relevance of enteropathogens in international travellers with and without diarrhoea are limited. Stool samples from 114 cases of diarrhoea in travellers returning from the tropics were collected for microbiological examination and PCR for norovirus genogroups I and II, enteroaggregative Escherichia coli (EAEC), and enterotoxigenic E. coli (ETEC) producing heat-labile toxin (LT) and heat-stable toxin (ST). Travel and laboratory data of cases were compared with those of 56 travellers without diarrhoea. Among cases, EAEC was found in 45% of stool samples, followed by LT-ETEC (20%), ST-ETEC (16%), Blastocystis hominis (15%), Campylobacter jejuni (12%), norovirus (11%), Giardia lamblia (6%), Shigella spp. (6%), and Salmonella spp., Cryptosporidium spp., and Cyclospora cayetanensis (3% each). However, only for EAEC, ST-ETEC, Blastocystis and Campylobacter was the prevalence significantly higher among cases than among controls. Co-infections were common: 61% for cases and 13% for controls. The most common travel destination was Asia (54%), followed by Africa (35%) and Latin America (9%). The highest relative risk for diarrhoea was calculated for travellers to West Africa, East Africa, and South Asia. In this study, EAEC, LT-ETEC and ST-ETEC were detected most frequently in cases of travellers' diarrhoea. Although enteric infections with EAEC, ST-ETEC and Campylobacter often cause diarrhoea, the pathogenetic relevance remains unclear for most of the other enteropathogens, because of significant prevalence rates also being seen in controls without diarrhoea and the high frequency of co-infections. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.