Level of Satisfaction of Older Persons with Their General Practitioner and Practice: Role of Complexity of Health Problems

PubMed Central

Poot, Antonius J.; den Elzen, Wendy P. J.; Blom, Jeanet W.; Gussekloo, Jacobijn

2014-01-01

Background Satisfaction is widely used to evaluate and direct delivery of medical care; a complicated relationship exists between patient satisfaction, morbidity and age. This study investigates the relationships between complexity of health problems and level of patient satisfaction of older persons with their general practitioner (GP) and practice. Methods and Findings This study is embedded in the ISCOPE (Integrated Systematic Care for Older Persons) study. Enlisted patients aged ≥75 years from 59 practices received a written questionnaire to screen for complex health problems (somatic, functional, psychological and social). For 2664 randomly chosen respondents (median age 82 years; 68% female) information was collected on level of satisfaction (satisfied, neutral, dissatisfied) with their GP and general practice, and demographic and clinical characteristics including complexity of health problems. Of all participants, 4% was dissatisfied with their GP care, 59% neutral and 37% satisfied. Between these three categories no differences were observed in age, gender, country of birth or education level. The percentage of participants dissatisfied with their GP care increased from 0.4% in those with 0 problem domains to 8% in those with 4 domains, i.e. having complex health problems (p<0.001). Per additional health domain with problems, the risk of being dissatisfied increased 1.7 times (95% CI 1.4–2.14; p<0.001). This was independent of age, gender, and demographic and clinical parameters (adjusted OR 1.4, 95% CI 1.1–1.8; p = 0.021). Conclusion In older persons, dissatisfaction with general practice is strongly correlated with rising complexity of health problems, independent of age, demographic and clinical parameters. It remains unclear whether complexity of health problems is a patient characteristic influencing the perception of care, or whether the care is unable to handle the demands of these patients. Prospective studies are needed to investigate the causal associations between care organization, patient characteristics, indicators of quality, and patient perceptions. PMID:24710557

Level of satisfaction of older persons with their general practitioner and practice: role of complexity of health problems.

PubMed

Poot, Antonius J; den Elzen, Wendy P J; Blom, Jeanet W; Gussekloo, Jacobijn

2014-01-01

Satisfaction is widely used to evaluate and direct delivery of medical care; a complicated relationship exists between patient satisfaction, morbidity and age. This study investigates the relationships between complexity of health problems and level of patient satisfaction of older persons with their general practitioner (GP) and practice. This study is embedded in the ISCOPE (Integrated Systematic Care for Older Persons) study. Enlisted patients aged ≥75 years from 59 practices received a written questionnaire to screen for complex health problems (somatic, functional, psychological and social). For 2664 randomly chosen respondents (median age 82 years; 68% female) information was collected on level of satisfaction (satisfied, neutral, dissatisfied) with their GP and general practice, and demographic and clinical characteristics including complexity of health problems. Of all participants, 4% was dissatisfied with their GP care, 59% neutral and 37% satisfied. Between these three categories no differences were observed in age, gender, country of birth or education level. The percentage of participants dissatisfied with their GP care increased from 0.4% in those with 0 problem domains to 8% in those with 4 domains, i.e. having complex health problems (p<0.001). Per additional health domain with problems, the risk of being dissatisfied increased 1.7 times (95% CI 1.4-2.14; p<0.001). This was independent of age, gender, and demographic and clinical parameters (adjusted OR 1.4, 95% CI 1.1-1.8; p = 0.021). In older persons, dissatisfaction with general practice is strongly correlated with rising complexity of health problems, independent of age, demographic and clinical parameters. It remains unclear whether complexity of health problems is a patient characteristic influencing the perception of care, or whether the care is unable to handle the demands of these patients. Prospective studies are needed to investigate the causal associations between care organization, patient characteristics, indicators of quality, and patient perceptions.

Is the integration of nutritional care in the different assistance levels possible? The Catalan experience. Clinical perspective

PubMed

Burgos Peláez, Rosa; Joaquin Ortiz, Clara; Vaqué Crusellas, Cristina

2017-05-08

Disease-related malnutrition is highly prevalent in pathologies commonly integrating care complexity. Healthcare models for complexity must include malnutrition detection and approaches, since it is a key factor which has great impact on the patient’s evolution and the consumption of healthcare resources. Malnourished patients present higher hospitalization, complication and mortality rates, higher demand of post-discharge social resources and higher hospital readmission frequency. Detecting malnutrition is necessary to implement a nutritional care program which might be used in any assistance level. The integration of health and social care and the development of information tools which are shared by the different assistance agents has allowed the development of a program for the management of disease-related malnutrition in patients with clinical complexity in Catalonia.

Skills in Clinical Communication: Are We Correctly Assessing Them at Undergraduate Level?

ERIC Educational Resources Information Center

Zamora Cervantes, Alberto; Carrión Ribas, Carme; Cordón Granados, Ferran; Galí Pla, Bibiana; Balló Peña, Elisabet; Quesada Sabate, Miquel; Grau Martin, Armand; Castro Guardiola, Antoni; Torrent Goñi, Silvia; Vargas Vila, Susanna; Vilert Garrofa, Esther; Subirats Bayego, Enric; Coll de Tuero, Gabriel; Muñoz Ortiz, Laura; Cerezo Goyeneche, Carlos; Torán Monserrat, Pere

2014-01-01

Traditional learning and assessment systems are overwhelmed when it comes to addressing the complex and multi-dimensional problems of clinical communication and professional practice. This paper shows results of a training program in clinical communication under Problem Based Learning (PBL) methodology and correlation between student…

Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.

PubMed

Steiman, Amanda J; Gladman, Dafna D; Ibañez, Dominique; Noamani, Babak; Landolt-Marticorena, Carolina; Urowitz, Murray B; Wither, Joan E

2015-12-01

Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) remain clinically quiescent for prolonged periods despite anti-dsDNA antibodies and/or low complements, indicating the presence of immune complexes. The immune mechanisms leading to this quiescence are unknown. However, in addition to activating complement, immune complex uptake by various cells leads to the production of interferon (IFN)-α and other proinflammatory factors that are also involved in tissue damage. Here we investigate whether production of these factors is reduced in SACQ patients. The levels of 5 IFN-induced genes and 19 cyto/chemokines were measured in SACQ patients and were compared with those in serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients. SACQ and SQCQ were defined as ≥ 2 years without clinical activity, with/without persistent serologic activity, respectively, and off corticosteroids/immunosuppressives. SACA was defined as disease activity compelling immunosuppression. Levels of OAS1, IFIT1, MX1, LY6E, and ISG15 were measured by quantitative real-time polymerase chain reaction (PCR) and a composite score (IFN-5) derived from this. Plasma cyto/chemokines were measured by Luminex assay. Nonparametric univariate and logistic regression analyses were conducted. There were no differences in gene expression or cyto/chemokine levels between SACQ and SQCQ patients. The SACQ IFN-5 score was significantly lower than that of SACA (p = 0.003) and was driven by SACQ status, not by autoantibody profile or disease duration. Levels of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 6, IL-10, IFN-γ-inducible protein 10, monocyte chemoattractant protein 1, and tumor necrosis factor-α were significantly lower in SACQ than SACA. The levels of proinflammatory factors in SACQ mirror those of SQCQ patients, indicating reduced production of these factors despite the presence of immune complexes.

Conceptual Complexity and Obsessionality in Bulimic College Women.

ERIC Educational Resources Information Center

Johnson, Nancy S.; Holloway, Elizabeth L.

1988-01-01

Examined relationship between bulimia, conceptual complexity, obsessional symptoms, and obsessional traits in 54 college women classified as bulimic-anorexic vomiters, normal-weight bulimic vomiters, clinical controls, and normal controls. Found both bulimic groups exhibited significantly lower levels of conceptual functioning, significantly…

Cumulative complexity: a functional, patient-centered model of patient complexity can improve research and practice.

PubMed

Shippee, Nathan D; Shah, Nilay D; May, Carl R; Mair, Frances S; Montori, Victor M

2012-10-01

To design a functional, patient-centered model of patient complexity with practical applicability to analytic design and clinical practice. Existing literature on patient complexity has mainly identified its components descriptively and in isolation, lacking clarity as to their combined functions in disrupting care or to how complexity changes over time. The authors developed a cumulative complexity model, which integrates existing literature and emphasizes how clinical and social factors accumulate and interact to complicate patient care. A narrative literature review is used to explicate the model. The model emphasizes a core, patient-level mechanism whereby complicating factors impact care and outcomes: the balance between patient workload of demands and patient capacity to address demands. Workload encompasses the demands on the patient's time and energy, including demands of treatment, self-care, and life in general. Capacity concerns ability to handle work (e.g., functional morbidity, financial/social resources, literacy). Workload-capacity imbalances comprise the mechanism driving patient complexity. Treatment and illness burdens serve as feedback loops, linking negative outcomes to further imbalances, such that complexity may accumulate over time. With its components largely supported by existing literature, the model has implications for analytic design, clinical epidemiology, and clinical practice. Copyright © 2012 Elsevier Inc. All rights reserved.

Construct validity of the pediatric evaluation of disability inventory computer adaptive test (PEDI-CAT) in children with medical complexity.

PubMed

Dumas, Helene M; Fragala-Pinkham, Maria A; Rosen, Elaine L; O'Brien, Jane E

2017-11-01

To assess construct (convergent and divergent) validity of the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in a sample of children with complex medical conditions. Demographics, clinical information, PEDI-CAT normative score, and the Post-Acute Acuity Rating for Children (PAARC) level were collected for all post-acute hospital admissions (n = 110) from 1 April 2015 to 1 March 2016. Correlations between the PEDI-CAT Daily Activities, Mobility, and Social/Cognitive domain scores for the total sample and across three age groups (infant, preschool, and school-age) were calculated. Differences in mean PEDI-CAT scores for each domain across two groups, children with "Less Complexity," or "More Complexity" based on PAARC level were examined. All correlations for the total sample and age subgroups were statistically significant and trends across age groups were evident with the stronger associations between domains for the infant group. Significant differences were found between mean PEDI-CAT Daily Activities, Mobility, and Social/Cognitive normative scores across the two complexity groups with children in the "Less Complex" group having higher PEDI-CAT scores for all domains. This study provides evidence indicating the PEDI-CAT can be used with confidence in capturing and differentiating children's level of function in a post-acute care setting. Implications for Rehabilitation The PEDI-CAT is measure of function for children with a variety of conditions and can be used in any clinical setting. Convergent validity of the PEDI-CAT's Daily Activities, Mobility, and Social/Cognitive domains was significant and particularly strong for infants and young children with medical complexity. The PEDI-CAT was able to discriminate groups of children with differing levels of medical complexity admitted to a pediatric post-acute care hospital.

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

The value and cost of complexity in predictive modelling: role of tissue anisotropic conductivity and fibre tracts in neuromodulation

NASA Astrophysics Data System (ADS)

Salman Shahid, Syed; Bikson, Marom; Salman, Humaira; Wen, Peng; Ahfock, Tony

2014-06-01

Objectives. Computational methods are increasingly used to optimize transcranial direct current stimulation (tDCS) dose strategies and yet complexities of existing approaches limit their clinical access. Since predictive modelling indicates the relevance of subject/pathology based data and hence the need for subject specific modelling, the incremental clinical value of increasingly complex modelling methods must be balanced against the computational and clinical time and costs. For example, the incorporation of multiple tissue layers and measured diffusion tensor (DTI) based conductivity estimates increase model precision but at the cost of clinical and computational resources. Costs related to such complexities aggregate when considering individual optimization and the myriad of potential montages. Here, rather than considering if additional details change current-flow prediction, we consider when added complexities influence clinical decisions. Approach. Towards developing quantitative and qualitative metrics of value/cost associated with computational model complexity, we considered field distributions generated by two 4 × 1 high-definition montages (m1 = 4 × 1 HD montage with anode at C3 and m2 = 4 × 1 HD montage with anode at C1) and a single conventional (m3 = C3-Fp2) tDCS electrode montage. We evaluated statistical methods, including residual error (RE) and relative difference measure (RDM), to consider the clinical impact and utility of increased complexities, namely the influence of skull, muscle and brain anisotropic conductivities in a volume conductor model. Main results. Anisotropy modulated current-flow in a montage and region dependent manner. However, significant statistical changes, produced within montage by anisotropy, did not change qualitative peak and topographic comparisons across montages. Thus for the examples analysed, clinical decision on which dose to select would not be altered by the omission of anisotropic brain conductivity. Significance. Results illustrate the need to rationally balance the role of model complexity, such as anisotropy in detailed current flow analysis versus value in clinical dose design. However, when extending our analysis to include axonal polarization, the results provide presumably clinically meaningful information. Hence the importance of model complexity may be more relevant with cellular level predictions of neuromodulation.

Development and initial outcomes of an upper gastrointestinal multidisciplinary clinic.

PubMed

Brown, Anna; Wylie, Neil; Rodgers, Michael; Casement, Jonathan; McIlree, Neil; Gray, Lindsay; Mulholland, Glen; Volkova, Vicki; van der Watt, Erna; Booth, Michael; Koea, Jonathan

2016-07-01

Patients with upper gastrointestinal cancer are often comorbid and require complex surgical treatments for their cancers, meaning that their preoperative assessment can be based around numerous outpatient assessments with multiple services. A multidisciplinary clinic (MDC) was developed for the assessment of patients with confirmed or suspected upper gastrointestinal cancers. Face-to-face meetings were held between stakeholder services at Waitemata District Health Board, and clinic resource allocated. Significant IT modification of existing clinic booking software was required. Between September 2014, and September 2015, there were a total of 165 new patient, and 710 follow-up appointments. All new patients were seen by a surgeon and then other specialties. Of the 165 new patient appointments, 146 (88%) patients had a definitive treatment plan in place and were cleared by anaesthesia and intensive care at the end of the clinic. Staff and patients report high levels of satisfaction for the clinic. A dedicated MDC has provided a single forum where complex patients can be reviewed, and a definitive treatment plan formulated in nearly 90% of patients, even when this involves multiple medical and paramedical specialties with high levels of patient and clinician satisfaction.

Complex analyses on clinical information systems using restricted natural language querying to resolve time-event dependencies.

PubMed

Safari, Leila; Patrick, Jon D

2018-06-01

This paper reports on a generic framework to provide clinicians with the ability to conduct complex analyses on elaborate research topics using cascaded queries to resolve internal time-event dependencies in the research questions, as an extension to the proposed Clinical Data Analytics Language (CliniDAL). A cascaded query model is proposed to resolve internal time-event dependencies in the queries which can have up to five levels of criteria starting with a query to define subjects to be admitted into a study, followed by a query to define the time span of the experiment. Three more cascaded queries can be required to define control groups, control variables and output variables which all together simulate a real scientific experiment. According to the complexity of the research questions, the cascaded query model has the flexibility of merging some lower level queries for simple research questions or adding a nested query to each level to compose more complex queries. Three different scenarios (one of them contains two studies) are described and used for evaluation of the proposed solution. CliniDAL's complex analyses solution enables answering complex queries with time-event dependencies at most in a few hours which manually would take many days. An evaluation of results of the research studies based on the comparison between CliniDAL and SQL solutions reveals high usability and efficiency of CliniDAL's solution. Copyright © 2018 Elsevier Inc. All rights reserved.

Dyspepsia treatment with Al compounds widely used in clinical practice — an animal model approach

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Canena, J.; Reis, J.; Santos, A. M.; Pinto, A. S.; Quina, M. G.; Reis, M. A.; Alves, L. C.

1996-04-01

The potential toxic effects of Al to organs and tissues used in drugs commonly applied in dyspepsia as therapeutic, have been studied. Brain, liver, kidney and serum samples obtained from Wistar rats treated with two commercial Al complexes were studied and compared with equivalent samples collected from healthy animals receiving a placebo. The major alterations found, connected with the persistent intake of medicaments based on Al compounds, are relative to the accumulation of Al in liver and kidney. Also, the Al levels increase in brain and serum of rats supplemented with one of the Al complexes used. In the liver and kidney samples analyzed alterations in the Cu and Zn content levels were observed. Furthermore, a tendency to the decrease of Fe content in kidney and an increase of the Mn levels in brain is observed. The elemental alterations found are probably related to the intake of the drugs tested and are dependent on the type of the Al complex administered. The results obtained suggest that the long term use of these medicaments in the clinical practice should be thought over.

Evaluation of the Vitek MS v3.0 Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry System for Identification of Mycobacterium and Nocardia Species.

PubMed

Body, Barbara A; Beard, Melodie A; Slechta, E Susan; Hanson, Kimberly E; Barker, Adam P; Babady, N Esther; McMillen, Tracy; Tang, Yi-Wei; Brown-Elliott, Barbara A; Iakhiaeva, Elena; Vasireddy, Ravikiran; Vasireddy, Sruthi; Smith, Terry; Wallace, Richard J; Turner, S; Curtis, L; Butler-Wu, Susan; Rychert, Jenna

2018-06-01

This multicenter study was designed to assess the accuracy and reproducibility of the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry system for identification of Mycobacterium and Nocardia species compared to DNA sequencing. A total of 963 clinical isolates representing 51 taxa were evaluated. In all, 663 isolates were correctly identified to the species level (69%), with another 231 (24%) correctly identified to the complex or group level. Fifty-five isolates (6%) could not be identified despite repeat testing. All of the tuberculous mycobacteria (45/45; 100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly identified at least to the group or complex level. However, not all species or subspecies within the M. tuberculosis , M. abscessus , and M. avium complexes and within the M. fortuitum and M. mucogenicum groups could be differentiated. Among the 312 Nocardia isolates tested, 236 (76%) were correctly identified to the species level, with an additional 44 (14%) correctly identified to the complex level. Species within the N. nova and N. transvalensis complexes could not always be differentiated. Eleven percent of the isolates (103/963) underwent repeat testing in order to get a final result. Identification of a representative set of Mycobacterium and Nocardia species was highly reproducible, with 297 of 300 (99%) replicates correctly identified using multiple kit lots, instruments, analysts, and sites. These findings demonstrate that the system is robust and has utility for the routine identification of mycobacteria and Nocardia in clinical practice. Copyright © 2018 American Society for Microbiology.

Lumbo-Pelvic-Hip Complex Pain in a Competitive Basketball Player

PubMed Central

Reiman, Michael P.; Cox, Kara D.; Jones, Kay S.; Byrd, J. W.

2011-01-01

Establishing the cause of lumbo-pelvic-hip complex pain is a challenge for many clinicians. This case report describes the mechanism of injury, diagnostic process, surgical management, and rehabilitation of a female high school basketball athlete who sustained an injury when falling on her right side. Diagnostics included clinical examination, radiography of the spine and hip joint, magnetic resonance imaging arthrogram, 3-dimensional computed tomography scan, and computed tomography of the hip joint. A systematic multidisciplinary clinical approach resulted in the patient’s return to previous functional levels. PMID:23015993

Developing and evaluating the implementation of a complex intervention: using mixed methods to inform the design of a randomised controlled trial of an oral healthcare intervention after stroke

PubMed Central

2011-01-01

Background Many interventions delivered within the stroke rehabilitation setting could be considered complex, though some are more complex than others. The degree of complexity might be based on the number of and interactions between levels, components and actions targeted within the intervention. The number of (and variation within) participant groups and the contexts in which it is delivered might also reflect the extent of complexity. Similarly, designing the evaluation of a complex intervention can be challenging. Considerations include the necessity for intervention standardisation, the multiplicity of outcome measures employed to capture the impact of a multifaceted intervention and the delivery of the intervention across different clinical settings operating within varying healthcare contexts. Our aim was to develop and evaluate the implementation of a complex, multidimensional oral health care (OHC) intervention for people in stroke rehabilitation settings which would inform the development of a randomised controlled trial. Methods After reviewing the evidence for the provision of OHC following stroke, multi-disciplinary experts informed the development of our intervention. Using both quantitative and qualitative methods we evaluated the implementation of the complex OHC intervention across patients, staff and service levels of care. We also adopted a pragmatic approach to patient recruitment, the completion of assessment tools and delivery of OHC, alongside an attention to the context in which it was delivered. Results We demonstrated the feasibility of implementing a complex OHC intervention across three levels of care. The complementary nature of the mixed methods approach to data gathering provided a complete picture of the implementation of the intervention and a detailed understanding of the variations within and interactions between the components of the intervention. Information on the feasibility of the outcome measures used to capture impact across a range of components was also collected, though some process orientated uncertainties including eligibility and recruitment rates remain to be further explored within a Phase II exploratory trial. Conclusions Complex interventions can be captured and described in a manner which facilitates evaluation in the form of exploratory and subsequently definitive clinical trials. If effective, the evidence captured relating to the intervention context will facilitate translation into clinical practice. PMID:21729277

A Novel Method for Assessing Task Complexity in Outpatient Clinical-Performance Measures.

PubMed

Hysong, Sylvia J; Amspoker, Amber B; Petersen, Laura A

2016-04-01

Clinical-performance measurement has helped improve the quality of health-care; yet success in attaining high levels of quality across multiple domains simultaneously still varies considerably. Although many sources of variability in care quality have been studied, the difficulty required to complete the clinical work itself has received little attention. We present a task-based methodology for evaluating the difficulty of clinical-performance measures (CPMs) by assessing the complexity of their component requisite tasks. Using Functional Job Analysis (FJA), subject-matter experts (SMEs) generated task lists for 17 CPMs; task lists were rated on ten dimensions of complexity, and then aggregated into difficulty composites. Eleven outpatient work SMEs; 133 VA Medical Centers nationwide. Clinical Performance: 17 outpatient CPMs (2000-2008) at 133 VA Medical Centers nationwide. Measure Difficulty: for each CPM, the number of component requisite tasks and the average rating across ten FJA complexity scales for the set of tasks comprising the measure. Measures varied considerably in the number of component tasks (M = 10.56, SD = 6.25, min = 5, max = 25). Measures of chronic care following acute myocardial infarction exhibited significantly higher measure difficulty ratings compared to diabetes or screening measures, but not to immunization measures ([Formula: see text] = 0.45, -0.04, -0.05, and -0.06 respectively; F (3, 186) = 3.57, p = 0.015). Measure difficulty ratings were not significantly correlated with the number of component tasks (r = -0.30, p = 0.23). Evaluating the difficulty of achieving recommended CPM performance levels requires more than simply counting the tasks involved; using FJA to assess the complexity of CPMs' component tasks presents an alternate means of assessing the difficulty of primary-care CPMs and accounting for performance variation among measures and performers. This in turn could be used in designing performance reward programs, or to match workflow to clinician time and effort.

Building clinical and organizational resilience to reconcile safety threats, tensions and trade-offs: insights from theory and evidence.

PubMed

Jeffs, Lianne; Tregunno, Deborah; MacMillan, Kathleen; Espin, Sherry

2009-01-01

Healthcare delivery settings are complex adaptive and tightly coupled, interrelated systems. Within the larger healthcare system, a key subsystem is the "clinical microsystem" level. It is at this level that clinicians are faced with high levels of uncertainty in their daily work - uncertainty that impacts the quality and safety of care that patients receive. The first aim of this paper is to enhance healthcare leaders' understanding of what is currently known about safety threats and strategies to manage the inherent tensions and trade-offs that occur in everyday practice. The second aim is to inform strategies that build clinical and organizational resilience through a multi-level framework derived from the collective theoretical and empirical work. Together, this information can strengthen safety practices throughout healthcare organizations.

Homoarginine—A prognostic indicator in adolescents and adults with complex congenital heart disease?

PubMed Central

Mueller, Marieke; Meinitzer, Andreas; Maerz, Winfried; Dschietzig, Thomas

2017-01-01

Background Homoarginine (hArg) has been shown to be of prognostic value in patients with chronic left heart failure. The present study aims to assess the clinical utility and prognostic value of hArg levels in patients with complex congenital heart disease (CHD). Methods Plasma hArg levels were measured in 143 patients with complex CHD and compared to clinical status, echocardiographic and laboratory parameters as well as the occurrence of adverse cardiac events. Results Median hArg levels were 1.5 μmol/l in CHD patients as compared to 1.70 μmol/l in healthy controls (p = 0.051). Median hArg levels were lowest in patients with Fontan palliation (1.27 μmol/l) and Eisenmenger physiology (0.99 μmol/l) and decreased with the severity of adverse cardiac events with lowest values found in patients prior to death or overt heart failure (0.89 μmol/l). According to ROC analysis, the most important predictors of adverse cardiac events were hArg levels (AUC 0.837, p<0.001, CI 0.726–0.947), NYHA class (AUC 0.800, p<0.001, CI 0.672–0.928) and NT-proBNP levels (AUC 0.780, p<0.001, CI 0.669–0.891). The occurrence of overt heart failure or death due to progressive heart failure were best predicted by NYHA class (AUC 0.945, p<0.001, CI 0.898–0.992), hArg levels (AUC 0.911, p<0.001, CI 0.850–0.971) and NT-proBNP levels (AUC 0.877, p<0.001, CI 0.791–0.962), respectively. Conclusion In patients with complex CHD, hArg levels can predict adverse cardiac events as reliably as or even better than NT-proBNP levels and thus might be of prognostic value in this subset of patients. PMID:28886170

Robotics: The next step?

PubMed

Broeders, Ivo A M J

2014-02-01

Robotic systems were introduced 15 years ago to support complex endoscopic procedures. The technology is increasingly used in gastro-intestinal surgery. In this article, literature on experimental- and clinical research is reviewed and ergonomic issues are discussed. literature review was based on Medline search using a large variety of search terms, including e.g. robot(ic), randomized, rectal, oesophageal, ergonomics. Review articles on relevant topics are discussed with preference. There is abundant evidence of supremacy in performing complex endoscopic surgery tasks when using the robot in an experimental setting. There is little high-level evidence so far on translation of these merits to clinical practice. Robotic systems may appear helpful in complex gastro-intestinal surgery. Moreover, dedicated computer based technology integrated in telepresence systems opens the way to integration of planning, diagnostics and therapy. The first high tech add-ons such as near infrared technology are under clinical evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Poly-Omic Prediction of Complex Traits: OmicKriging

PubMed Central

Wheeler, Heather E.; Aquino-Michaels, Keston; Gamazon, Eric R.; Trubetskoy, Vassily V.; Dolan, M. Eileen; Huang, R. Stephanie; Cox, Nancy J.; Im, Hae Kyung

2014-01-01

High-confidence prediction of complex traits such as disease risk or drug response is an ultimate goal of personalized medicine. Although genome-wide association studies have discovered thousands of well-replicated polymorphisms associated with a broad spectrum of complex traits, the combined predictive power of these associations for any given trait is generally too low to be of clinical relevance. We propose a novel systems approach to complex trait prediction, which leverages and integrates similarity in genetic, transcriptomic, or other omics-level data. We translate the omic similarity into phenotypic similarity using a method called Kriging, commonly used in geostatistics and machine learning. Our method called OmicKriging emphasizes the use of a wide variety of systems-level data, such as those increasingly made available by comprehensive surveys of the genome, transcriptome, and epigenome, for complex trait prediction. Furthermore, our OmicKriging framework allows easy integration of prior information on the function of subsets of omics-level data from heterogeneous sources without the sometimes heavy computational burden of Bayesian approaches. Using seven disease datasets from the Wellcome Trust Case Control Consortium (WTCCC), we show that OmicKriging allows simple integration of sparse and highly polygenic components yielding comparable performance at a fraction of the computing time of a recently published Bayesian sparse linear mixed model method. Using a cellular growth phenotype, we show that integrating mRNA and microRNA expression data substantially increases performance over either dataset alone. Using clinical statin response, we show improved prediction over existing methods. PMID:24799323

Metrics and tools for consistent cohort discovery and financial analyses post-transition to ICD-10-CM

PubMed Central

Boyd, Andrew D; ‘John’ Li, Jianrong; Kenost, Colleen; Joese, Binoy; Min Yang, Young; Kalagidis, Olympia A; Zenku, Ilir; Saner, Donald; Bahroos, Neil; Lussier, Yves A

2015-01-01

In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, the ninth revision) diagnosis codes are commonly used to identify patient cohorts and to conduct financial analyses related to disease. In October 2015, the healthcare system of the United States will transition to ICD-10-CM (the tenth revision) diagnosis codes. One challenge posed to clinical researchers and other analysts is conducting diagnosis-related queries across datasets containing both coding schemes. Further, healthcare administrators will manage growth, trends, and strategic planning with these dually-coded datasets. The majority of the ICD-9-CM to ICD-10-CM translations are complex and nonreciprocal, creating convoluted representations and meanings. Similarly, mapping back from ICD-10-CM to ICD-9-CM is equally complex, yet different from mapping forward, as relationships are likewise nonreciprocal. Indeed, 10 of the 21 top clinical categories are complex as 78% of their diagnosis codes are labeled as “convoluted” by our analyses. Analysis and research related to external causes of morbidity, injury, and poisoning will face the greatest challenges due to 41 745 (90%) convolutions and a decrease in the number of codes. We created a web portal tool and translation tables to list all ICD-9-CM diagnosis codes related to the specific input of ICD-10-CM diagnosis codes and their level of complexity: “identity” (reciprocal), “class-to-subclass,” “subclass-to-class,” “convoluted,” or “no mapping.” These tools provide guidance on ambiguous and complex translations to reveal where reports or analyses may be challenging to impossible. Web portal: http://www.lussierlab.org/transition-to-ICD9CM/ Tables annotated with levels of translation complexity: http://www.lussierlab.org/publications/ICD10to9 PMID:25681260

Barriers to Clinical Trial Enrollment in Racial and Ethnic Minority Patients With Cancer

PubMed Central

Hamel, Lauren M.; Penner, Louis A.; Albrecht, Terrance L.; Heath, Elisabeth; Gwede, Clement K.; Eggly, Susan

2016-01-01

Background Clinical trials that study cancer are essential for testing the safety and effectiveness of promising treatments, but most people with cancer never enroll in a clinical trial — a challenge exemplified in racial and ethnic minorities. Underenrollment of racial and ethnic minorities reduces the generalizability of research findings and represents a disparity in access to high-quality health care. Methods Using a multilevel model as a framework, potential barriers to trial enrollment of racial and ethnic minorities were identified at system, individual, and interpersonal levels. Exactly how each level directly or indirectly contributes to doctor–patient communication was also reviewed. Selected examples of implemented interventions are included to help address these barriers. We then propose our own evidence-based intervention addressing barriers at the individual and interpersonal levels. Results Barriers to enrolling a diverse population of patients in clinical trials are complex and multilevel. Interventions focused at each level have been relatively successful, but multilevel interventions have the greatest potential for success. Conclusion To increase the enrollment of racial and ethnic minorities in clinical trials, future interventions should address barriers at multiple levels. PMID:27842322

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

Traditional Chinese medicine: potential approaches from modern dynamical complexity theories.

PubMed

Ma, Yan; Zhou, Kehua; Fan, Jing; Sun, Shuchen

2016-03-01

Despite the widespread use of traditional Chinese medicine (TCM) in clinical settings, proving its effectiveness via scientific trials is still a challenge. TCM views the human body as a complex dynamical system, and focuses on the balance of the human body, both internally and with its external environment. Such fundamental concepts require investigations using system-level quantification approaches, which are beyond conventional reductionism. Only methods that quantify dynamical complexity can bring new insights into the evaluation of TCM. In a previous article, we briefly introduced the potential value of Multiscale Entropy (MSE) analysis in TCM. This article aims to explain the existing challenges in TCM quantification, to introduce the consistency of dynamical complexity theories and TCM theories, and to inspire future system-level research on health and disease.

Preparing new nurses with complexity science and problem-based learning.

PubMed

Hodges, Helen F

2011-01-01

Successful nurses function effectively with adaptability, improvability, and interconnectedness, and can see emerging and unpredictable complex problems. Preparing new nurses for complexity requires a significant change in prevalent but dated nursing education models for rising graduates. The science of complexity coupled with problem-based learning and peer review contributes a feasible framework for a constructivist learning environment to examine real-time systems data; explore uncertainty, inherent patterns, and ambiguity; and develop skills for unstructured problem solving. This article describes a pilot study of a problem-based learning strategy guided by principles of complexity science in a community clinical nursing course. Thirty-five senior nursing students participated during a 3-year period. Assessments included peer review, a final project paper, reflection, and a satisfaction survey. Results were higher than expected levels of student satisfaction, increased breadth and analysis of complex data, acknowledgment of community as complex adaptive systems, and overall higher level thinking skills than in previous years. 2011, SLACK Incorporated.

Diagnostic reference levels and complexity indices in interventional radiology: a national programme.

PubMed

Ruiz-Cruces, R; Vano, E; Carrera-Magariño, F; Moreno-Rodriguez, F; Soler-Cantos, M M; Canis-Lopez, M; Hernández-Armas, J; Diaz-Romero, F J; Rosales-Espizua, F; Fernandez-Soto, J M; Sanchez-Casanueva, R; Martin-Palanca, A; Perez-Martinez, M; Gil-Agudo, A; Zarca-Diaz, M A; Parra-Osorio, V; Muñoz Ruiz-Canela, J J; Moreno-Sanchez, T; Lopez-Medina, A; Moreno-Saiz, C; Galan-Montenegro, P; Gallego-Beuter, J J; Gonzalez-de-Garay, M; Zapata-Jimenez, J C; Pastor-Vega, J M; Cañete, S

2016-12-01

To propose national diagnostic reference levels (DRLs) for interventional radiology and to evaluate the impact of the procedural complexity on patient doses. Eight interventional radiology units from Spanish hospitals were involved in this project. The participants agreed to undergo common quality control procedures for X-ray systems. Kerma area product (KAP) was collected from a sample of 1,649 procedures. A consensus document established the criteria to evaluate the complexity of seven types of procedures. DRLs were set as the 3rd quartile of KAP values. The KAP (3rd quartile) in Gy cm 2 for the procedures included in the survey were: lower extremity arteriography (n = 784) 78; renal arteriography (n = 37) 107; transjugular hepatic biopsies (THB) (n = 30) 45; biliary drainage (BD) (n = 314) 30; uterine fibroid embolization (UFE) (n = 56) 214; colon endoprostheses (CE) (n = 31) 169; hepatic chemoembolization (HC) (n = 269) 303; femoropopliteal revascularization (FR) (n = 62) 119; and iliac stent (n = 66) 170. The complexity involved the increases in the following KAP factors from simple to complex procedures: THB x4; BD x13; UFE x3; CE x3; HC x5; FR x5 and IS x4. The evaluation of the procedure complexity in patient doses will allow the proper use of DRLs for the optimization of interventional radiology. • National DRLs for interventional procedures have been proposed given level of complexity • For clinical audits, the level of complexity should be taken into account. • An evaluation of the complexity levels of the procedure should be made.

An Integrative Social-Cognitive Developmental Model of Supervision for Substance Abuse Counselors-in-Training

ERIC Educational Resources Information Center

Sias, Shari M.; Lambie, Glenn W.

2008-01-01

Substance abuse counselors (SACs) at higher levels of social-cognitive maturity manage complex situations and perform counselor-related tasks more effectively than individuals at lower levels of development. This article presents an integrative clinical supervision model designed to promote the social-cognitive maturity (ego development;…

The role (or not) of economic evaluation at the micro level: can Bourdieu's theory provide a way forward for clinical decision-making?

PubMed

Lessard, Chantale; Contandriopoulos, André-Pierre; Beaulieu, Marie-Dominique

2010-06-01

Despite increasing interest in health economic evaluation, investigations have shown limited use by micro (clinical) level decision-makers. A considerable amount of health decisions take place daily at the point of the clinical encounter; especially in primary care. Since every decision has an opportunity cost, ignoring economic information in family physicians' (FPs) decision-making may have a broad impact on health care efficiency. Knowledge translation of economic evaluation is often based on taken-for-granted assumptions about actors' interests and interactions, neglecting much of the complexity of social reality. Health economics literature frequently assumes a rational and linear decision-making process. Clinical decision-making is in fact a complex social, dynamic, multifaceted process, involving relationships and contextual embeddedness. FPs are embedded in complex social networks that have a significant impact on skills, attitudes, knowledge, practices, and on the information being used. Because of their socially constructed nature, understanding preferences, professional culture, practices, and knowledge translation requires serious attention to social reality. There has been little exploration by health economists of whether the problem may be more fundamental and reside in a misunderstanding of the process of decision-making. There is a need to enhance our understanding of the role of economic evaluation in decision-making from a disciplinary perspective different than health economics. This paper argues for a different conceptualization of the role of economic evaluation in FPs' decision-making, and proposes Bourdieu's sociological theory as a research framework. Bourdieu's theory of practice illustrates how the context-sensitive nature of practice must be understood as a socially constituted practical knowledge. The proposed approach could substantially contribute to a more complex understanding of the role of economic evaluation in FPs' decision-making. Copyright 2010 Elsevier Ltd. All rights reserved.

Inferring Clinical Workflow Efficiency via Electronic Medical Record Utilization

PubMed Central

Chen, You; Xie, Wei; Gunter, Carl A; Liebovitz, David; Mehrotra, Sanjay; Zhang, He; Malin, Bradley

2015-01-01

Complexity in clinical workflows can lead to inefficiency in making diagnoses, ineffectiveness of treatment plans and uninformed management of healthcare organizations (HCOs). Traditional strategies to manage workflow complexity are based on measuring the gaps between workflows defined by HCO administrators and the actual processes followed by staff in the clinic. However, existing methods tend to neglect the influences of EMR systems on the utilization of workflows, which could be leveraged to optimize workflows facilitated through the EMR. In this paper, we introduce a framework to infer clinical workflows through the utilization of an EMR and show how such workflows roughly partition into four types according to their efficiency. Our framework infers workflows at several levels of granularity through data mining technologies. We study four months of EMR event logs from a large medical center, including 16,569 inpatient stays, and illustrate that over approximately 95% of workflows are efficient and that 80% of patients are on such workflows. At the same time, we show that the remaining 5% of workflows may be inefficient due to a variety of factors, such as complex patients. PMID:26958173

Low-molecular-weight heparin biosimilars: potential implications for clinical practice. Australian Low-Molecular-Weight Heparin Biosimilar Working Group (ALBW).

PubMed

Nandurkar, H; Chong, B; Salem, H; Gallus, A; Ferro, V; McKinnon, R

2014-05-01

A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors.

PubMed

Zhao, Y-K; Jia, C-M; Yuan, G-J; Liu, W; Qiu, Y; Zhu, Q-G

2015-06-29

We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

Phenotypic Characteristics Associated with Virulence of Clinical Isolates from the Sporothrix Complex

PubMed Central

Almeida-Paes, Rodrigo; de Oliveira, Luã Cardoso; Oliveira, Manoel Marques Evangelista; Gutierrez-Galhardo, Maria Clara; Nosanchuk, Joshua Daniel; Zancopé-Oliveira, Rosely Maria

2015-01-01

The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis. PMID:25961005

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

NASA Astrophysics Data System (ADS)

Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

2015-01-01

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

Mood states modulate complexity in heartbeat dynamics: A multiscale entropy analysis

NASA Astrophysics Data System (ADS)

Valenza, G.; Nardelli, M.; Bertschy, G.; Lanata, A.; Scilingo, E. P.

2014-07-01

This paper demonstrates that heartbeat complex dynamics is modulated by different pathological mental states. Multiscale entropy analysis was performed on R-R interval series gathered from the electrocardiogram of eight bipolar patients who exhibited mood states among depression, hypomania, and euthymia, i.e., good affective balance. Three different methodologies for the choice of the sample entropy radius value were also compared. We show that the complexity level can be used as a marker of mental states being able to discriminate among the three pathological mood states, suggesting to use heartbeat complexity as a more objective clinical biomarker for mental disorders.

Cystatin C–Adiponectin Complex in Plasma Associates with Coronary Plaque Instability

PubMed Central

Matsuoka, Tetsuro; Kayama, Kento; Onishi, Sumire; Matsuo, Natsumi

2017-01-01

Aim: Adiponectin (APN) is an adipocyte-derived bioactive molecule with antiatherogenic properties. We previously reported that cystatin C (CysC) abolished the anti-atherogenic effects of APN. We aimed to elucidate the clinical significance of CysC–APN complex in patients with coronary artery disease (CAD). Methods: We enrolled 43 stable CAD male patients to examine the relationship between CysC–APN complex and coronary plaque characteristics. Serum was immunoprecipitated by the anti-APN antibody and immunoblotted by the anti-CysC antibody to demonstrate the presence of CysC–APN complexes in vivo. To confirm their binding in vitro, HEK293T cell lysates overexpressing myc-APN and FLAG-CysC were immunoprecipitated with an anti-myc or anti-FLAG antibody, followed by immunoblotting with an anti-APN or anti-CysC antibody. Results: CysC was identified as a specific co-immunoprecipitant with APN by the anti-APN antibody in human serum. In vitro, FLAG-CysC was co-immunoprecipitated with myc-APN by the antimyc antibody and myc-APN was co-immunoprecipitated with FLAG-CysC by the anti-FLAG antibody. Among CAD patients, serum CysC–APN complex levels negatively correlated with fibrotic components of coronary plaques and positively correlated with either necrotic or lipidic plus necrotic components. Plaque burden negatively correlated with serum APN levels but not serum CysC–APN complex levels. Serum CysC levels had no association with plaque characteristics. In multivariate analysis, CysC–APN complex levels were identified as the strongest negative factor for fibrotic components and the strongest positive factor for both necrotic and lipidic plus necrotic components. Conclusion: Measuring serum CysC–APN complex levels is helpful for evaluating coronary plaque instability in CAD patients. PMID:28321013

Overview on Clinical Relevance of Intra-Tumor Heterogeneity.

PubMed

Stanta, Giorgio; Bonin, Serena

2018-01-01

Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH) is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

Surgical management of congenital heart disease: correlation between hospital costs and the Aristotle complexity score.

PubMed

Sinzobahamvya, N; Kopp, T; Photiadis, J; Arenz, C; Schindler, E; Haun, C; Hraska, V; Asfour, B

2010-09-01

Hospital costs are expected to correlate with clinical complexity. Do costs for congenital heart surgery correlate with Aristotle complexity scores? 442 inpatient stays in 2008 were evaluated. Aristotle scores and levels were determined. Costs were estimated according to the German Institute for Hospital Reimbursement system. Pearson and Spearman R correlation coefficients and corresponding goodness-of-fit regression coefficients R2 were calculated. Mean basic and comprehensive Aristotle scores were 7.60 +/- 2.74 and 9.23 +/- 2.94 points, respectively. Mean expenses per hospital stay amounted to 29,369 +/- 30,823 Euros. Aristotle basic and comprehensive scores and levels were positively correlated with hospital costs. With a Spearman R of 1 and related R2 of 0.9436, scores of the 6 Aristotle comprehensive levels correlated best. Mean hospital reimbursement was 26,412 +/- 17,962 Euros. Compensation was higher than expenses for patients in comprehensive levels 1 to 3, but much lower for those in levels 4 to 6. Aristotle comprehensive complexity scores were highly correlated with hospital costs. The Aristotle score could be used as a scale to establish the correct reimbursement after congenital heart surgery. Georg Thieme Verlag KG Stuttgart, New York.

Quantifying the need for enhanced case management for TB patients as part of TB cohort audit in the North West of England: a descriptive study.

PubMed

Tucker, Angela; Mithoo, Jeniffer; Cleary, Paul; Woodhead, Mark; MacPherson, Peter; Wingfield, Tom; Davies, Stefanie; Wake, Carolyn; McMaster, Paddy; Bertel Squire, S

2017-11-15

Patients with TB have diverse and often challenging clinical and social needs that may hamper successful treatment outcomes. Understanding the need for additional support during treatment (enhanced case management, or ECM) is important for workforce capacity planning. North West England TB Cohort Audit (TBCA) has introduced a 4-level ECM classification system (ECM 0-3) to quantify the need for ECM in the region. This study describes the data from the first 2 years of ECM classification. Data collected between April 2013 and July 2015 were used to analyse the proportions of patients allocated to each ECM level and the prevalence of social and clinical factors indicating need for ECM. Single variable and multivariable logistic regression models were constructed to examine the association between ECM level and treatment outcome. Of 1714 notified cases 99.8% were assigned an ECM level: 31% ECM1, 19% ECM2 and 14% ECM3. The most common factors indicating need for ECM were language barriers (20.3%) and clinical complexity (16.9%). 1342/1493 (89.9%) of drug-sensitive, non-CNS cases completed treatment within 12 months. Patients in ECM2 and 3 were less likely to complete treatment at 12 months than patients in ECM0 (adjusted OR 0.47 [95% CI 0.27-0.84] and 0.23 [0.13-0.41] respectively). Use of TBCA to quantify different levels of need for ECM is feasible and has demonstrated that social and clinical complexity is common in the region. Results will inform regional workforce planning and assist development of innovative methods to improve treatment outcomes in these vulnerable groups.

Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders.

PubMed

Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

2017-01-01

Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self's experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal.

Laboratory equipment maintenance contracts.

PubMed

Boudreau, D A; Scheer, W D; Catrou, P G

1985-12-01

The increasing level of technical sophistication and complexity found in clinical laboratory instrumentation today more than ever demands careful attention to maintenance service needs. The time-worn caution for careful definition of requirements for acquisition of a system should also carry over to acquisition of maintenance service. Guidelines are presented for specifications of terms and conditions for maintenance service from the perspective of the laboratorian in the automated clinical laboratory.

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

PubMed Central

Koit, Andre; Ounpuu, Lyudmila; Klepinin, Aleksandr; Chekulayev, Vladimir; Timohhina, Natalja; Tepp, Kersti; Puurand, Marju; Truu, Laura; Heck, Karoliina; Valvere, Vahur; Guzun, Rita

2017-01-01

We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures. PMID:28781720

Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill.

PubMed

Jiang, Dongsheng; Kong, Weihong; Jiang, Joanna J

2017-01-01

Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genetic Organization of the Chromosome Region Surrounding mecA in Clinical Staphylococcal Strains: Role of IS431-Mediated mecI Deletion in Expression of Resistance in mecA-Carrying, Low-Level Methicillin- Resistant Staphylococcus haemolyticus

PubMed Central

Katayama, Yuki; Ito, Teruyo; Hiramatsu, Keiichi

2001-01-01

We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S. haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS431L was located to the left of an intact mecI gene, forming the structure IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L was associated with the deletion of mecI and mecR1, forming the structure IS431L-ΔmecR1-mecA-IS431mec, designated the class C mecA gene complex. Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS431L-class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC, 16 to 64 mg/liter). The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indicated that the mecI-encoded repressor function is responsible for the low-level methicillin resistance of some S. haemolyticus clinical strains and that the IS431-mediated mecI gene deletion causes the expression of methicillin resistance through the derepression of mecA gene transcription. PMID:11408208

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.

PubMed

Ringman, John M; Frautschy, Sally A; Teng, Edmond; Begum, Aynun N; Bardens, Jenny; Beigi, Maryam; Gylys, Karen H; Badmaev, Vladimir; Heath, Dennis D; Apostolova, Liana G; Porter, Verna; Vanek, Zeba; Marshall, Gad A; Hellemann, Gerhard; Sugar, Catherine; Masterman, Donna L; Montine, Thomas J; Cummings, Jeffrey L; Cole, Greg M

2012-01-01

Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex(®) with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex(®) was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex(®) in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. ClinicalTrials.gov Identifier: NCT00099710.

Integrating Genomic Analysis with the Genetic Basis of Gene Expression: Preliminary Evidence of the Identification of Causal Genes for Cardiovascular and Metabolic Traits Related to Nutrition in Mexicans123

PubMed Central

Bastarrachea, Raúl A.; Gallegos-Cabriales, Esther C.; Nava-González, Edna J.; Haack, Karin; Voruganti, V. Saroja; Charlesworth, Jac; Laviada-Molina, Hugo A.; Veloz-Garza, Rosa A.; Cardenas-Villarreal, Velia Margarita; Valdovinos-Chavez, Salvador B.; Gomez-Aguilar, Patricia; Meléndez, Guillermo; López-Alvarenga, Juan Carlos; Göring, Harald H. H.; Cole, Shelley A.; Blangero, John; Comuzzie, Anthony G.; Kent, Jack W.

2012-01-01

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics. PMID:22797999

Clinical value of natriuretic peptides in chronic kidney disease.

PubMed

Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

2015-01-01

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Inhalational botulism in rhesus macaques exposed to botulinum neurotoxin complex serotypes A1 and B1.

PubMed

Sanford, Daniel C; Barnewall, Roy E; Vassar, Michelle L; Niemuth, Nancy; Metcalfe, Karen; House, Robert V; Henderson, Ian; Shearer, Jeffry D

2010-09-01

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD(50)) and to estimate 50% lethal exposure concentrations relative to time (LCt(50)) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD(50) and LCt(50) for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.

Inhalational Botulism in Rhesus Macaques Exposed to Botulinum Neurotoxin Complex Serotypes A1 and B1▿ †

PubMed Central

Sanford, Daniel C.; Barnewall, Roy E.; Vassar, Michelle L.; Niemuth, Nancy; Metcalfe, Karen; House, Robert V.; Henderson, Ian; Shearer, Jeffry D.

2010-01-01

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD50) and to estimate 50% lethal exposure concentrations relative to time (LCt50) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD50 and LCt50 for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication. PMID:20660138

Metrics and tools for consistent cohort discovery and financial analyses post-transition to ICD-10-CM.

PubMed

Boyd, Andrew D; Li, Jianrong John; Kenost, Colleen; Joese, Binoy; Yang, Young Min; Kalagidis, Olympia A; Zenku, Ilir; Saner, Donald; Bahroos, Neil; Lussier, Yves A

2015-05-01

In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, the ninth revision) diagnosis codes are commonly used to identify patient cohorts and to conduct financial analyses related to disease. In October 2015, the healthcare system of the United States will transition to ICD-10-CM (the tenth revision) diagnosis codes. One challenge posed to clinical researchers and other analysts is conducting diagnosis-related queries across datasets containing both coding schemes. Further, healthcare administrators will manage growth, trends, and strategic planning with these dually-coded datasets. The majority of the ICD-9-CM to ICD-10-CM translations are complex and nonreciprocal, creating convoluted representations and meanings. Similarly, mapping back from ICD-10-CM to ICD-9-CM is equally complex, yet different from mapping forward, as relationships are likewise nonreciprocal. Indeed, 10 of the 21 top clinical categories are complex as 78% of their diagnosis codes are labeled as "convoluted" by our analyses. Analysis and research related to external causes of morbidity, injury, and poisoning will face the greatest challenges due to 41 745 (90%) convolutions and a decrease in the number of codes. We created a web portal tool and translation tables to list all ICD-9-CM diagnosis codes related to the specific input of ICD-10-CM diagnosis codes and their level of complexity: "identity" (reciprocal), "class-to-subclass," "subclass-to-class," "convoluted," or "no mapping." These tools provide guidance on ambiguous and complex translations to reveal where reports or analyses may be challenging to impossible.Web portal: http://www.lussierlab.org/transition-to-ICD9CM/Tables annotated with levels of translation complexity: http://www.lussierlab.org/publications/ICD10to9. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Coagulation and fibrinolysis in inflammatory bowel disease and in giant cell arteritis.

PubMed

Vrij, Anton A; Rijken, Joop; van Wersch, Jan W J; Stockbrügger, Reinhold W

2003-01-01

In inflammatory bowel disease (IBD), gut microvascular thrombosis as well as thromboembolic complications have repeatedly been observed. We examined the long-term course of markers of coagulation and fibrinolysis in relation to clinical disease activity. In a prospective study, prothrombin fragment 1 and 2 (F1.2), thrombin-antithrombin complex (TAT), antithrombin, D-dimer, plasmin-alpha(2)-antiplasmin complex (PAP) and plasminogen activator inhibitor-1 (PAI-1) were measured in 20 patients with Crohn's disease (CD), 18 with ulcerative colitis (UC), and 19 with giant cell arteritis during active and inactive disease, as well as in 51 controls without inflammation. Levels of F1.2, TAT, D-dimer, PAP and PAI-1 were significantly higher in active versus inactive CD and UC. However, even after 12 months of follow-up, in CD and UC the mean levels of F1.2, D-dimer and PAP were significantly higher than the levels of the controls. Levels of F1.2, D-dimer and PAP were markedly raised for a long time in clinically inactive IBD, underlining a chronic state of hypercoagulation and enhanced fibrinolysis. Copyright 2003 S. Karger AG, Basel

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

PubMed

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Instability of monoclonal myeloma protein may be identified as susceptibility to penetration and binding by newly synthesized Congo red derivatives.

PubMed

Spólnik, Paweł; Konieczny, Leszek; Piekarska, Barbara; Rybarska, Janina; Stopa, Barbara; Zemanek, Grzegorz; Król, Marcin; Roterman, Irena

2004-06-01

Monoclonal myeloma proteins often have an abnormal, unstable structure, and tend to aggregate with fatal clinical consequences. A method for early clinical identification of this aggregation tendency is impatiently awaited. This work proposes the use of supramolecular dyes as specific ligands to reveal protein instability. Disclosure of excessive polypeptide chain flexibility in unstable monoclonal proteins, leading to increased susceptibility to penetration by foreign compounds, appeared possible when new supramolecular Congo red-derived dyes with different protein-binding capabilities were used for complexation. Two basic protein instability levels, local and global, were differentiated by comparing the extent of protein loading with dye and the subsequent electrophoretic migration rate of the complexes. A simple electrophoretic test is proposed for assessment of the instability of monoclonal proteins in clinical conditions.

Complex contexts and relationships affect clinical decisions in group therapy.

PubMed

Tasca, Giorgio A; Mcquaid, Nancy; Balfour, Louise

2016-09-01

Clinical errors tend to be underreported even though examining them can provide important training and professional development opportunities. The group therapy context may be prone to clinician errors because of the added complexity within which therapists work and patients receive treatment. We discuss clinical errors that occurred within a group therapy in which a patient for whom group was not appropriate was admitted to the treatment and then was not removed by the clinicians. This was countertherapeutic for both patient and group. Two clinicians were involved: a clinical supervisor who initially assessed and admitted the patient to the group, and a group therapist. To complicate matters, the group therapy occurred within the context of a clinical research trial. The errors, possible solutions, and recommendations are discussed within Reason's Organizational Accident Model (Reason, 2000). In particular, we discuss clinician errors in the context of countertransference and clinician heuristics, group therapy as a local work condition that complicates clinical decision-making, and the impact of the research context as a latent organizational factor. We also present clinical vignettes from the pregroup preparation, group therapy, and supervision. Group therapists are more likely to avoid errors in clinical decisions if they engage in reflective practice about their internal experiences and about the impact of the context in which they work. Therapists must keep in mind the various levels of group functioning, especially related to the group-as-a-whole (i.e., group composition, cohesion, group climate, and safety) when making complex clinical decisions in order to optimize patient outcomes. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Managing Complex Change in Clinical Study Metadata

PubMed Central

Brandt, Cynthia A.; Gadagkar, Rohit; Rodriguez, Cesar; Nadkarni, Prakash M.

2004-01-01

In highly functional metadata-driven software, the interrelationships within the metadata become complex, and maintenance becomes challenging. We describe an approach to metadata management that uses a knowledge-base subschema to store centralized information about metadata dependencies and use cases involving specific types of metadata modification. Our system borrows ideas from production-rule systems in that some of this information is a high-level specification that is interpreted and executed dynamically by a middleware engine. Our approach is implemented in TrialDB, a generic clinical study data management system. We review approaches that have been used for metadata management in other contexts and describe the features, capabilities, and limitations of our system. PMID:15187070

Identification of Acinetobacter seifertii isolated from Bolivian hospitals.

PubMed

Cerezales, Mónica; Xanthopoulou, Kyriaki; Ertel, Julia; Nemec, Alexandr; Bustamante, Zulema; Seifert, Harald; Gallego, Lucia; Higgins, Paul G

2018-06-01

Acinetobacter seifertii is a recently described species that belongs to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. It has been recovered from clinical samples and is sometimes associated with antimicrobial resistance determinants. We present here the case of three A. seifertii clinical isolates which were initially identified as Acinetobacter sp. by phenotypic methods but no identification at the species level was achieved using semi-automated identification methods. The isolates were further analysed by whole genome sequencing and identified as A. seifertii. Due to the fact that A. seifertii has been isolated from serious infections such as respiratory tract and bloodstream infections, we emphasize the importance of correctly identifying isolates of the genus Acinetobacter at the species level to gain a deeper knowledge of their prevalence and clinical impact.

Analyses of the Complexity of Patients Undergoing Attended Polysomnography in the Era of Home Sleep Apnea Tests

PubMed Central

Colaco, Brendon; Herold, Daniel; Johnson, Matthew; Roellinger, Daniel; Naessens, James M.; Morgenthaler, Timothy I.

2018-01-01

Study Objectives: Health care complexity includes dimensions of patient comorbidity and the level of services needed to meet patient demands. Home sleep apnea tests (HSAT) are increasingly used to test medically uncomplicated patients suspected of having moderate to severe obstructive sleep apnea (OSA). Patients with significant comorbidities or other sleep disorders are not candidates for HSAT and require attended in-center polysomnography. We hypothesized that this trend would result in increasingly complex patients being studied in sleep centers. Methods: Our study had two parts. To ascertain trends in sleep patient comorbidity, we used administrative diagnostic codes from patients undergoing polysomnography at the Mayo Clinic Center for Sleep Medicine from 2005 to June 2015 to calculate the Charlson and the Elixhauser comorbidity indices. We measured the level of services provided in two ways: (1) in a subset of patients from the past 2 months of 2015, we evaluated correlation of these morbidity indices with an internally developed Polysomnogram Clinical Index (PSGCI) rating anticipated patient care needs from 0 to 3 and (2) we measured the sleep study complexity based on polysomnography protocol design. Results: In 43,780 patients studied from 2005 to June 2015, the Charlson index increased from a mean of 1.38 to 1.88 (3.1% per year, P < .001) and the mean Elixhauser index increased from 2.61 to 3.35 (2.5% per year, P < .001). Both comorbidity indices were significantly higher at the highest (Level 3) level of the PSGCI (P < .001), and sleep study complexity increased over time. Conclusions: The complexity of patients undergoing attended polysomnography has increased by 28% to 36% over the past decade as measured by validated comorbidity indices, and these indices correlate with the complexity of rendered care during polysomnography. These findings have implications for increasing requirements for staffing, monitoring capabilities, and facility design of future sleep centers. Commentary: A commentary on this article appears in this issue on page 499. Citation: Colaco B, Herold D, Johnson M, Roellinger D, Naessens JM, Morgenthaler TI. Analyses of the complexity of patients undergoing attended polysomnography in the era of home sleep apnea tests. J Clin Sleep Med. 2018;14(4):631–639. PMID:29609716

Impact of clinical inertia on cardiovascular risk factors in patients with diabetes.

PubMed

Whitford, David L; Al-Anjawi, Hussam A; Al-Baharna, Marwa M

2014-07-01

To determine whether clinical inertia is associated with simpler interventions occurring more often than complex changes and the association between clinical inertia and outcomes. Prevalence of clinical inertia over a 30 month period for hyperglycaemia, hypertension and dyslipidaemia was calculated in a random sample (n=334) of patients attending a diabetes clinic. Comparisons between prevalence of clinical inertia and outcomes for each condition were examined using parametric tests of association. There was less clinical inertia in hyperglycaemia (29% of consultations) compared with LDL (80% of consultations) and systolic BP (68% of consultations). Consultations where therapy was intensified had a greater reduction in risk factor levels than when no change was made. No association was found between treatment intensity scores and changes in HbA1c, LDL or blood pressure over 30 months. Physicians are no more likely to intervene in conditions where simple therapeutic changes are necessary as opposed to complex changes. Greater clinical inertia leads to poorer outcomes. There continues to be substantial clinical inertia in routine clinical practice. Physicians should adopt a holistic approach to cardiovascular risk reduction in patients with diabetes, adhere more closely to established management guidelines and emphasize personal individualized target setting. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Using systems thinking to support clinical system transformation.

PubMed

Best, Allan; Berland, Alex; Herbert, Carol; Bitz, Jennifer; van Dijk, Marlies W; Krause, Christina; Cochrane, Douglas; Noel, Kevin; Marsden, Julian; McKeown, Shari; Millar, John

2016-05-16

Purpose - The British Columbia Ministry of Health's Clinical Care Management initiative was used as a case study to better understand large-scale change (LSC) within BC's health system. Using a complex system framework, the purpose of this paper is to examine mechanisms that enable and constrain the implementation of clinical guidelines across various clinical settings. Design/methodology/approach - Researchers applied a general model of complex adaptive systems plus two specific conceptual frameworks (realist evaluation and system dynamics mapping) to define and study enablers and constraints. Focus group sessions and interviews with clinicians, executives, managers and board members were validated through an online survey. Findings - The functional themes for managing large-scale clinical change included: creating a context to prepare clinicians for health system transformation initiatives; promoting shared clinical leadership; strengthening knowledge management, strategic communications and opportunities for networking; and clearing pathways through the complexity of a multilevel, dynamic system. Research limitations/implications - The action research methodology was designed to guide continuing improvement of implementation. A sample of initiatives was selected; it was not intended to compare and contrast facilitators and barriers across all initiatives and regions. Similarly, evaluating the results or process of guideline implementation was outside the scope; the methods were designed to enable conversations at multiple levels - policy, management and practice - about how to improve implementation. The study is best seen as a case study of LSC, offering a possible model for replication by others and a tool to shape further dialogue. Practical implications - Recommended action-oriented strategies included engaging local champions; supporting local adaptation for implementation of clinical guidelines; strengthening local teams to guide implementation; reducing change fatigue; ensuring adequate resources; providing consistent communication especially for front-line care providers; and supporting local teams to demonstrate the clinical value of the guidelines to their colleagues. Originality/value - Bringing a complex systems perspective to clinical guideline implementation resulted in a clear understanding of the challenges involved in LSC.

Semantic enrichment of clinical models towards semantic interoperability. The heart failure summary use case.

PubMed

Martínez-Costa, Catalina; Cornet, Ronald; Karlsson, Daniel; Schulz, Stefan; Kalra, Dipak

2015-05-01

To improve semantic interoperability of electronic health records (EHRs) by ontology-based mediation across syntactically heterogeneous representations of the same or similar clinical information. Our approach is based on a semantic layer that consists of: (1) a set of ontologies supported by (2) a set of semantic patterns. The first aspect of the semantic layer helps standardize the clinical information modeling task and the second shields modelers from the complexity of ontology modeling. We applied this approach to heterogeneous representations of an excerpt of a heart failure summary. Using a set of finite top-level patterns to derive semantic patterns, we demonstrate that those patterns, or compositions thereof, can be used to represent information from clinical models. Homogeneous querying of the same or similar information, when represented according to heterogeneous clinical models, is feasible. Our approach focuses on the meaning embedded in EHRs, regardless of their structure. This complex task requires a clear ontological commitment (ie, agreement to consistently use the shared vocabulary within some context), together with formalization rules. These requirements are supported by semantic patterns. Other potential uses of this approach, such as clinical models validation, require further investigation. We show how an ontology-based representation of a clinical summary, guided by semantic patterns, allows homogeneous querying of heterogeneous information structures. Whether there are a finite number of top-level patterns is an open question. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

What are specialist mental health clinician attitudes to guideline recommendations for the treatment of depression in young people?

PubMed

Hetrick, Sarah E; Simmons, Magenta; Thompson, Andrew; Parker, Alexandra G

2011-11-01

We sought to examine potential barriers to the use of evidence-based guidelines for youth depression in a tertiary specialist mental health service, as part of an initiative to implement evidence based practice within the service. This was a qualitative study adopting a social constructionist perspective using focus groups. The focus groups, conducted with all clinicians (medical and allied health), were audiotaped, transcribed and thematic analysis was undertaken. Clinicians were asked about the barriers to implementing four key recommendations from the National Institute for Health and Clinical Excellence (NICE) guidelines. Barriers existed at (i) the individual clinician level; (ii) the clinical level in terms of the presentation of young people; and (iii) the service level. The key individual clinician level barrier was a stated belief that the guidelines were not relevant to the young people presenting to the service, with little evidence to guide practice. Related, the main barrier with regard to the clinical presentation was the severity and complexity of this presentation, often making the delivery of interventions like cognitive behavioural therapy (CBT) difficult. At the service level, a lack of integration with primary and secondary level care meant sequencing interventions according to guideline recommendations was difficult. There is a clear imperative to develop the evidence base to ensure that effective treatments for young people aged up to 25 years with severe and complex disorders that include comorbid conditions, suicide risk and psychosocial difficulties are investigated and disseminated. Furthermore, this work has highlighted the need for greater investment in models of care that ensure integration between existing primary and secondary care and enhanced specialist early intervention mental health services for young people.

Temporal abstraction and temporal Bayesian networks in clinical domains: a survey.

PubMed

Orphanou, Kalia; Stassopoulou, Athena; Keravnou, Elpida

2014-03-01

Temporal abstraction (TA) of clinical data aims to abstract and interpret clinical data into meaningful higher-level interval concepts. Abstracted concepts are used for diagnostic, prediction and therapy planning purposes. On the other hand, temporal Bayesian networks (TBNs) are temporal extensions of the known probabilistic graphical models, Bayesian networks. TBNs can represent temporal relationships between events and their state changes, or the evolution of a process, through time. This paper offers a survey on techniques/methods from these two areas that were used independently in many clinical domains (e.g. diabetes, hepatitis, cancer) for various clinical tasks (e.g. diagnosis, prognosis). A main objective of this survey, in addition to presenting the key aspects of TA and TBNs, is to point out important benefits from a potential integration of TA and TBNs in medical domains and tasks. The motivation for integrating these two areas is their complementary function: TA provides clinicians with high level views of data while TBNs serve as a knowledge representation and reasoning tool under uncertainty, which is inherent in all clinical tasks. Key publications from these two areas of relevance to clinical systems, mainly circumscribed to the latest two decades, are reviewed and classified. TA techniques are compared on the basis of: (a) knowledge acquisition and representation for deriving TA concepts and (b) methodology for deriving basic and complex temporal abstractions. TBNs are compared on the basis of: (a) representation of time, (b) knowledge representation and acquisition, (c) inference methods and the computational demands of the network, and (d) their applications in medicine. The survey performs an extensive comparative analysis to illustrate the separate merits and limitations of various TA and TBN techniques used in clinical systems with the purpose of anticipating potential gains through an integration of the two techniques, thus leading to a unified methodology for clinical systems. The surveyed contributions are evaluated using frameworks of respective key features. In addition, for the evaluation of TBN methods, a unifying clinical domain (diabetes) is used. The main conclusion transpiring from this review is that techniques/methods from these two areas, that so far are being largely used independently of each other in clinical domains, could be effectively integrated in the context of medical decision-support systems. The anticipated key benefits of the perceived integration are: (a) during problem solving, the reasoning can be directed at different levels of temporal and/or conceptual abstractions since the nodes of the TBNs can be complex entities, temporally and structurally and (b) during model building, knowledge generated in the form of basic and/or complex abstractions, can be deployed in a TBN. Copyright © 2014 Elsevier B.V. All rights reserved.

Telehealth on advanced networks.

PubMed

Wilson, Laurence S; Stevenson, Duncan R; Cregan, Patrick

2010-01-01

We address advanced Internet for complex telehealth applications by reviewing four hospital-based broadband telehealth projects and identifying common threads. These projects were conducted in Australia under a 6-year research project on broadband Internet applications. Each project addressed specific clinical needs and its development was guided by the clinicians involved. Each project was trialed in the field and evaluated against the initial requirements. The four projects covered remote management of a resuscitation team in a district hospital, remote guidance and interpretation of echocardiography, virtual-reality-based instructor-student surgical training, and postoperative outpatient consultations following pediatric surgery. Each was characterized by a high level of interpersonal communication, a high level of clinical expertise, and multiple participants. Each made use of multiple high-quality video and audio links and shared real-time access to clinical data. Four common threads were observed. Each application provided a high level of usability and task focus because the design and use of broadband capability was aimed directly to meet the clinicians' needs. Each used the media quality available over broadband to convey words, gestures, body movements, and facial expressions to support communication and a sense of presence among the participants. Each required a complex information space shared among the participants, including real-time access to stored patient data and real-time interactive access to the patients themselves. Finally, each application supported the social and organizational aspects of their healthcare focus, creating and maintaining relationships between the various participants, and this was done by placing the telehealth application into a wider functioning clinical context. These findings provide evidence for a significantly enhanced role for appropriate telemedicine systems running on advanced networks, in a wider range of clinical applications, more deeply integrated into healthcare systems.

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.

The 'species complex' issue in clinically relevant fungi: A case study in Scedosporium apiospermum.

PubMed

Chen, Min; Zeng, Jingsi; De Hoog, G Sybren; Stielow, Benjamin; Gerrits Van Den Ende, A H G; Liao, Wanqing; Lackner, Michaela

2016-02-01

The genus Scedosporium currently comprises six species, Scedosporium apiospermum, Scedosporium boydii, Pseudallescheria angusta, Scedosporium minutisporum, Scedosporium dehoogii, and Scedosporium aurantiacum, most of which can be distinguished with the primary fungal DNA barcode, the ITS1/2 region of the rDNA gene cluster. In the present study, four additional genetic loci were explored from a phylogenetic point of view enabling a barcoding approach based on K2P pairwise distances to resolve the taxa Scedosporium. We included partial γ-actin (ACT), β-tubulin (BT2), elongation factor 1α (TEF1), and the small ribosomal protein 60S L10 (L1) (RP60S). Phylogenetic inference of each marker individually showed that four out of six species within Scedosporium can be distinguished unambiguously, while strains of S. apiospermum, S. boydii, and P. angusta showed occasional recombination, and accordingly, no genealogical concordance between markers was obtainable. We defined S. apiospermum, S. boydii, and P. angusta as the 'S. apiospermum species complex' since observed differences were not consistent between lineages, and no clinical differences are known between entities within the complex. While BT2 revealed the best performance among the genetic loci tested at the lineage level, barcoding of the ITS region is sufficient for distinction of all entities in Scedosporium at the species or 'complex' level. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders

PubMed Central

Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

2017-01-01

Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self’s experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal. PMID:29255430

Putting the puzzle together: the role of ‘problem definition’ in complex clinical judgement

PubMed Central

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

2017-01-01

CONTEXT We teach judgement in pieces; that is, we talk about each aspect separately (patient, plan, resources, technique, etc.). We also let trainees figure out how to put the pieces together. In complex situations, this might be problematic. Using data from a drawing-based study on surgeons’ experiences with complex situations, we explore the notion of ‘problem definition’ in real-world clinical judgement using the theoretical lens of systems engineering. METHODS ‘Emergence’, the sensitising concept for analysis, is rooted in two key systems premises: that person and context are inseparable and that what emerges is an act of choice. Via a ‘gallery walk’ we used these premises to perform analysis on individual drawings as well as cross-comparisons of multiple drawings. Our focus was to understand similarities and differences among the vantage points used by multiple surgeons. RESULTS In this paper we challenge two assumptions from current models of clinical judgement: that experts hold a fixed and static definition of the problem and that consequently the focus of the expert’s work is on solving the problem. Each situation described by our participants revealed different but complementary perspectives of what a surgical problem might come to be: from concerns about ensuring standard of care, to balancing personal emotions versus care choices, to coordinating resources, and to maintaining control while in the midst of personality clashes. CONCLUSION We suggest that it is only at the situation and system level, not at the individual level, that we are able to appreciate the nuances of defining the problem when experts make judgements during real-world complex situations. PMID:27943366

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

PubMed

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

2017-02-01

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

Remote Monitoring for Follow-up of Patients with Cardiac Implantable Electronic Devices

PubMed Central

Morichelli, Loredana; Varma, Niraj

2014-01-01

Follow-up of patients with cardiac implantable electronic devices is challenging due to the increasing number and technical complexity of devices coupled to increasing clinical complexity of patients. Remote monitoring (RM) offers the opportunity to optimise clinic workflow and to improve device monitoring and patient management. Several randomised clinical trials and registries have demonstrated that RM may reduce number of hospital visits, time required for patient follow-up, physician and nurse time, hospital and social costs. Furthermore, patient retention and adherence to follow-up schedule are significantly improved by RM. Continuous wireless monitoring of data stored in the device memory with automatic alerts allows early detection of device malfunctions and of events requiring clinical reaction, such as atrial fibrillation, ventricular arrhythmias and heart failure. Early reaction may improve patient outcome. RM is easy to use and patients showed a high level of acceptance and satisfaction. Implementing RM in daily practice may require changes in clinic workflow. To this purpose, new organisational models have been introduced. In spite of a favourable cost:benefit ratio, RM reimbursement still represents an issue in several European countries. PMID:26835079

Quality in transitional care of the elderly: Key challenges and relevant improvement measures

PubMed Central

Storm, Marianne; Siemsen, Inger Margrete D.; Laugaland, Kristin; Dyrstad, Dagrunn Nåden; Aase, Karina

2014-01-01

Introduction Elderly people aged over 75 years with multifaceted care needs are often in need of hospital treatment. Transfer across care levels for this patient group increases the risk of adverse events. The aim of this paper is to establish knowledge of quality in transitional care of the elderly in two Norwegian hospital regions by identifying issues affecting the quality of transitional care and based on these issues suggest improvement measures. Methodology Included in the study were elderly patients (75+) receiving health care in the municipality admitted to hospital emergency department or discharged to community health care with hip fracture or with a general medical diagnosis. Participant observations of admission and discharge transitions (n = 41) were carried out by two researchers. Results Six main challenges with belonging descriptions have been identified: (1) next of kin (bridging providers, advocacy, support, information brokering), (2) patient characteristics (level of satisfaction, level of insecurity, complex clinical conditions), (3) health care personnel's competence (professional, system, awareness of others’ roles), (4) information exchange (oral, written, electronic), (5) context (stability, variability, change incentives, number of patient handovers) and (6) patient assessment (complex clinical picture, patient description, clinical assessment). Conclusion Related to the six main challenges, several measures have been suggested to improve quality in transitional care, e.g. information to and involvement of patients and next of kin, staff training, standardisation of routines and inter-organisational staff meetings. PMID:24868196

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Using mediation techniques to manage conflict and create healthy work environments.

PubMed

Gerardi, Debra

2004-01-01

Healthcare organizations must find ways for managing conflict and developing effective working relationships to create healthy work environments. The effects of unresolved conflict on clinical outcomes, staff retention, and the financial health of the organization lead to many unnecessary costs that divert resources from clinical care. The complexity of delivering critical care services makes conflict resolution difficult. Developing collaborative working relationships helps to manage conflict in complex environments. Working relationships are based on the ability to deal with differences. Dealing with differences requires skill development and techniques for balancing interests and communicating effectively. Techniques used by mediators are effective for resolving disputes and developing working relationships. With practice, these techniques are easily transferable to the clinical setting. Listening for understanding, reframing, elevating the definition of the problem, and forming clear agreements can foster working relationships, decrease the level of conflict, and create healthy work environments that benefit patients and professionals.

Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.

PubMed

Woodruff, Prescott G; Agusti, Alvar; Roche, Nicolas; Singh, Dave; Martinez, Fernando J

2015-05-02

Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological complexity and to help with the development of new treatment alternatives and, importantly, a reclassification of complex diseases. All these developments should pave the way towards personalised treatment of patients with COPD in the clinic. Copyright © 2015 Elsevier Ltd. All rights reserved.

The genetic background of hypertensive, septic rats determines outcome improvement with antibiotic and G-CSF prophylaxis.

PubMed

Bauhofer, Artur; Tischer, Bjirn; Middeke, Martin; Plaul, Ulrike; Lorenz, Wilfried; Torossian, Alexander

2003-10-01

Hypertension is proposed as a risk factor among others (high age, diabetes mellitus, and pre- and intraoperative bleeding) for adverse outcomes, such as severe infections, leading to sepsis and to multiple organ failure as the most deleterious complication. Hypertension was modeled with spontaneous hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats and the infective complication by polymicrobial, peritoneal contamination, and infection (PCI). The concept of clinic modeling randomized trials was used to simulate clinical complexity, including a relevant antibiotic prophylaxis in combination with granulocyte-colony stimulating factor (G-CSF) and clinical trial conditions. Outcome parameters were: survival, systemic cytokines (protein), and organ-specific cytokine levels (mRNA). With low complexity (no prophylaxis), 28% of the animals in the Wistar and 50% in the SHR group survived (P=0.17). Tumor necrosis factor-alpha levels were lower in the liver of SHR vs. Wistar rats with PCI (P<0.01). The anti-inflammatory cytokine interleukin (IL)-10 was expressed on a higher level in SHR with PCI compared with Wistar rats (P<0.01). With increased complexity (antibiotic and G-CSF prophylaxis) the survival rate was increased from 50% in Wistar rats to 89% in SHR (P<0.01) and the mRNA expression of IL-6 was decreased in the kidney of SHR (P<0.05). Survival rate was 44% in the DS rats vs. 67% of the Wistar rats (P=0.18). The mRNA expression of tumor necrosis factor-alpha and IL-10 was reduced (P<0.01) by pretreatment in the liver of DS rats with PCI. The hypertensive, genetically distinct SHR and DS rats express different patterns of pro- and anti-inflammatory cytokine levels after PCI. G-CSF and antibiotic prophylaxis increases only in SHR survival and decreases IL-6 mRNA expression in the kidney significantly.

Readability of informed consent forms in clinical trials conducted in a skin research center

PubMed Central

Samadi, Aniseh; Asghari, Fariba

2016-01-01

Obtaining informed consents is one of the most fundamental principles in conducting a clinical trial. In order for the consent to be informed, the patient must receive and comprehend the information appropriately. Complexity of the consent form is a common problem that has been shown to be a major barrier to comprehension for many patients. The objective of this study was to assess the readability of different templates of informed consent forms (ICFs) used in clinical trials in the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran, Iran. This study was conducted on ICFs of 45 clinical trials of the CRTSDL affiliated with Tehran University of Medical Sciences. ICFs were tested for reading difficulty, using the readability assessments formula adjusted for the Persian language including the Flesch–Kincaid reading ease score, Flesch–Kincaid grade level, and Gunning fog index. Mean readability score of the whole text of ICFs as well as their 7 main information parts were calculated. The mean ± SD Flesch Reading Ease score for all ICFs was 31.96 ± 5.62 that is in the difficult range. The mean ± SD grade level was calculated as 10.71 ± 1.8 (8.23–14.09) using the Flesch–Kincaid formula and 14.64 ± 1.22 (12.67–18.27) using the Gunning fog index. These results indicate that the text is expected to be understandable for an average student in the 11th grade, while the ethics committee recommend grade level 8 as the standard readability level for ICFs. The results showed that the readability scores of ICFs assessed in our study were not in the acceptable range. This means they were too complex to be understood by the general population. Ethics committees must examine the simplicity and readability of ICFs used in clinical trials. PMID:27471590

Reframing Person-Centered Nursing Care for Persons With Dementia

PubMed Central

Penrod, Janice; Yu, Fang; Kolanowski, Ann; Fick, Donna M.; Loeb, Susan J.; Hupcey, Judith E.

2010-01-01

Alzheimer’s dementia manifests in a complex clinical presentation that has been addressed from both biomedical and phenomenological perspectives. Although each of these paradigmatic perspectives has contributed to advancement of the science, neither is adequate for theoretically framing a person-centered approach to nursing care. The need-driven dementia-compromised behavior (NDB) model is discussed as an exemplar of midrange nursing theory that promotes the integration of these paradigmatic views to promote a new level of excellence in person-centered dementia care. Clinical application of the NDB promotes a new level of praxis, or thoughtful action, in the care of persons with dementia. PMID:17378465

Verification of monitor unit calculations for non-IMRT clinical radiotherapy: report of AAPM Task Group 114.

PubMed

Stern, Robin L; Heaton, Robert; Fraser, Martin W; Goddu, S Murty; Kirby, Thomas H; Lam, Kwok Leung; Molineu, Andrea; Zhu, Timothy C

2011-01-01

The requirement of an independent verification of the monitor units (MU) or time calculated to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance. The need for and value of such a verification was obvious when calculations were performed by hand using look-up tables, and the verification was achieved by a second person independently repeating the calculation. However, in a modern clinic using CT/MR/PET simulation, computerized 3D treatment planning, heterogeneity corrections, and complex calculation algorithms such as convolution/superposition and Monte Carlo, the purpose of and methodology for the MU verification have come into question. In addition, since the verification is often performed using a simpler geometrical model and calculation algorithm than the primary calculation, exact or almost exact agreement between the two can no longer be expected. Guidelines are needed to help the physicist set clinically reasonable action levels for agreement. This report addresses the following charges of the task group: (1) To re-evaluate the purpose and methods of the "independent second check" for monitor unit calculations for non-IMRT radiation treatment in light of the complexities of modern-day treatment planning. (2) To present recommendations on how to perform verification of monitor unit calculations in a modern clinic. (3) To provide recommendations on establishing action levels for agreement between primary calculations and verification, and to provide guidance in addressing discrepancies outside the action levels. These recommendations are to be used as guidelines only and shall not be interpreted as requirements.

Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

PubMed

Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

2014-01-01

Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

Comparison of two commercial carbapenemase gene confirmatory assays in multiresistant Enterobacteriaceae and Acinetobacter baumannii-complex.

PubMed

Rösner, Stephan; Gehlweiler, Kevin; Küsters, Uta; Kolbert, Mathias; Hübner, Kirsten; Pfennigwerth, Niels; Mack, Dietrich

2018-01-01

Multidrug-resistant Gram-negative bacilli (MDR-GNB) producing carbapenemases are increasing at an alarming speed. Rapid confirmation of carbapenemase type will be an important diagnostic step in clinical microbiology laboratories not only to reduce the risk of transmissions but also for optimising antibiotic therapy in the future. We compared diagnostic reliability of two commercially available molecular assays (Check-Direct CPE vs. AID line probe assay) for detection and typing of carbapenemase genes in 80 well-characterized isolates of MDR-GNB. Respective strains were isolated in various clinical specimens at our clinical microbiology laboratory. The reference standard included confirmation of carbapenemase-production at the molecular level at the German National Reference Laboratory for Multidrug-resistant Gram-negative bacteria (Ruhr-University Bochum, Germany). 53 Enterobacteriaceae and 27 members of the A. baumannii-complex were used in this study. The tested assays appeared highly reliable to confirm carbapenemase-producing Enterobacteriaceae (CPE) with respective sensitivities of 97.7%, but are currently unsuitable for analysis of members of the A. baumannii-complex. Both assays are easy to perform and rapid tools for confirmation and typing of the most common carbapenemase genes in Enterobacteriaceae. Implementation should be possible for any clinical microbiology laboratory with Check-Direct CPE being easier to handle and having less technological requirements.

Clinical Complexity in Medicine: A Measurement Model of Task and Patient Complexity.

PubMed

Islam, R; Weir, C; Del Fiol, G

2016-01-01

Complexity in medicine needs to be reduced to simple components in a way that is comprehensible to researchers and clinicians. Few studies in the current literature propose a measurement model that addresses both task and patient complexity in medicine. The objective of this paper is to develop an integrated approach to understand and measure clinical complexity by incorporating both task and patient complexity components focusing on the infectious disease domain. The measurement model was adapted and modified for the healthcare domain. Three clinical infectious disease teams were observed, audio-recorded and transcribed. Each team included an infectious diseases expert, one infectious diseases fellow, one physician assistant and one pharmacy resident fellow. The transcripts were parsed and the authors independently coded complexity attributes. This baseline measurement model of clinical complexity was modified in an initial set of coding processes and further validated in a consensus-based iterative process that included several meetings and email discussions by three clinical experts from diverse backgrounds from the Department of Biomedical Informatics at the University of Utah. Inter-rater reliability was calculated using Cohen's kappa. The proposed clinical complexity model consists of two separate components. The first is a clinical task complexity model with 13 clinical complexity-contributing factors and 7 dimensions. The second is the patient complexity model with 11 complexity-contributing factors and 5 dimensions. The measurement model for complexity encompassing both task and patient complexity will be a valuable resource for future researchers and industry to measure and understand complexity in healthcare.

Implications of the behavioral approach to hypnosis.

PubMed

Starker, S

1975-07-01

The findings of behaviorally oriented research regarding the importance of cognitive-motivational variables in hypnosis are examined and some clinical and theoretical implications are explored. Hypnosis seems usefully conceptualized as a complex configuration or gestalt of interacting variables on several different levels, for example, cognitive, motivational, social, physiologic.

Factors Associated With Emergency Department Visits: A Multistate Analysis of Adult Fee-for-Service Medicaid Beneficiaries.

PubMed

Agarwal, Parul; Bias, Thomas K; Madhavan, Suresh; Sambamoorthi, Nethra; Frisbee, Stephanie; Sambamoorthi, Usha

2016-04-27

The objective of this study was to examine the association of patient- and county-level factors with the emergency department (ED) visits among adult fee-for-service (FFS) Medicaid beneficiaries residing in Maryland, Ohio, and West Virginia. A cross-sectional design using retrospective observational data was implemented. Patient-level data were obtained from 2010 Medicaid Analytic eXtract files. Information on county-level health-care resources was obtained from the Area Health Resource file and County Health Rankings file. In adjusted analyses, the following patient-level factors were associated with higher number of ED visits: African Americans (incidence rate ratios [IRR] = 1.47), Hispanics (IRR = 1.63), polypharmacy (IRR = 1.89), and tobacco use (IRR = 2.23). Patients with complex chronic illness had a higher number of ED visits (IRR = 3.33). The county-level factors associated with ED visits were unemployment rate (IRR = 0.94) and number of urgent care clinics (IRR = 0.96). Patients with complex healthcare needs had a higher number of ED visits as compared to those without complex healthcare needs. The study results provide important baseline context for future policy analysis studies around Medicaid expansion options.

Bioinformatics/biostatistics: microarray analysis.

PubMed

Eichler, Gabriel S

2012-01-01

The quantity and complexity of the molecular-level data generated in both research and clinical settings require the use of sophisticated, powerful computational interpretation techniques. It is for this reason that bioinformatic analysis of complex molecular profiling data has become a fundamental technology in the development of personalized medicine. This chapter provides a high-level overview of the field of bioinformatics and outlines several, classic bioinformatic approaches. The highlighted approaches can be aptly applied to nearly any sort of high-dimensional genomic, proteomic, or metabolomic experiments. Reviewed technologies in this chapter include traditional clustering analysis, the Gene Expression Dynamics Inspector (GEDI), GoMiner (GoMiner), Gene Set Enrichment Analysis (GSEA), and the Learner of Functional Enrichment (LeFE).

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

PubMed

Cristancho, Sayra; Lingard, Lorelei; Regehr, Glenn

2017-02-01

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

Expertise in Clinical Psychology. The Effects of University Training and Practical Experience on Expertise in Clinical Psychology

PubMed Central

Vollmer, Sabine; Spada, Hans; Caspar, Franz; Burri, Salome

2013-01-01

How do university training and subsequent practical experience affect expertise in clinical psychology? To answer this question we developed methods to assess psychological knowledge and the competence to diagnose, construct case conceptualizations, and plan psychotherapeutic treatment: a knowledge test and short case studies in a first study, and a complex, dynamically evolving case study in the second study. In our cross-sectional studies, psychology students, trainees in a certified postgraduate psychotherapist curriculum, and behavior therapists with more than 10 years of experience were tested (100 in total: 20 each of novice, intermediate, and advanced university students, postgraduate trainees, and therapists). Clinical knowledge and competence increased up to the level of trainees but unexpectedly decreased at the level of experienced therapists. We discuss the results against the background of expertise research and the training of clinical psychologists (in Germany). Important factors for the continuing professional development of psychotherapists are proposed. PMID:23543213

Bridging the gap between biologic, individual, and macroenvironmental factors in cancer: a multilevel approach.

PubMed

Lynch, Shannon M; Rebbeck, Timothy R

2013-04-01

To address the complex nature of cancer occurrence and outcomes, approaches have been developed to simultaneously assess the role of two or more etiologic agents within hierarchical levels including the: (i) macroenvironment level (e.g., health care policy, neighborhood, or family structure); (ii) individual level (e.g., behaviors, carcinogenic exposures, socioeconomic factors, and psychologic responses); and (iii) biologic level (e.g., cellular biomarkers and inherited susceptibility variants). Prior multilevel approaches tend to focus on social and environmental hypotheses, and are thus limited in their ability to integrate biologic factors into a multilevel framework. This limited integration may be related to the limited translation of research findings into the clinic. We propose a "Multi-level Biologic and Social Integrative Construct" (MBASIC) to integrate macroenvironment and individual factors with biology. The goal of this framework is to help researchers identify relationships among factors that may be involved in the multifactorial, complex nature of cancer etiology, to aid in appropriate study design, to guide the development of statistical or mechanistic models to study these relationships, and to position the results of these studies for improved intervention, translation, and implementation. MBASIC allows researchers from diverse fields to develop hypotheses of interest under a common conceptual framework, to guide transdisciplinary collaborations, and to optimize the value of multilevel studies for clinical and public health activities.

Effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, on glycemic control in patients with Type 2 diabetes mellitus: a case series.

PubMed

Kim, Jiman; Byun, A Ri; Kwon, Seungwon

2014-12-01

Diabetes mellitus has significant effects on the human body. Recently, herbal medicines have received attention as complementary anti-diabetic agents on the basis of the results of several experimental studies. We present a series of 38 cases that demonstrate the positive effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, in lowering blood sugar levels in patients with uncontrolled type 2 diabetes mellitus. We reviewed the medical records of 38 patients treated with YRGBD. The types and doses of other hypoglycemic agents administered to the patients remained unchanged during treatment with YRGBD. After YRGBD therapy, the glycated haemoglobin level decreased from 76.16±19.90mmol/mol (9.11±1.82%) to 51.21±8.82mmol/mol (6.84±0.81%). There was a statistically significant difference between the glycated haemoglobin levels measured before and after treatment (paired t test, p<0.001). In the present study, we show the clinical effects of YRGBD on blood sugar control in patients with type 2 diabetes mellitus. Further clinical studies investigating the effects of YRGBD are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases

PubMed Central

Montgomery, McKale R.; Leyva, Kathryn J.

2016-01-01

Histone deacetylase (HDAC) inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials for several other diseases. In addition to influencing gene expression, HDAC enzymes also function as part of large, multisubunit complexes which have many nonhistone targets, alter signaling at the cellular and systemic levels, and result in divergent and cell-type specific effects. Thus, the effects of HDAC inhibitor treatment are too intricate to completely understand with current knowledge but the ability of HDAC inhibitors to modulate the immune system presents intriguing therapeutic possibilities. This review will explore the complexity of HDAC inhibitor treatment at the cellular and systemic levels and suggest strategies for effective use of HDAC inhibitors in biomedical research, focusing on the ability of HDAC inhibitors to modulate the immune system. The possibility of combining the documented anticancer effects and newly emerging immunomodulatory effects of HDAC inhibitors represents a promising new combinatorial therapeutic approach for HDAC inhibitor treatments. PMID:27556043

Clinical importance of personality difficulties: diagnostically sub-threshold personality disorders.

PubMed

Karukivi, Max; Vahlberg, Tero; Horjamo, Kalle; Nevalainen, Minna; Korkeila, Jyrki

2017-01-14

Current categorical classification of personality disorders has been criticized for overlooking the dimensional nature of personality and that it may miss some sub-threshold personality disturbances of clinical significance. We aimed to evaluate the clinical importance of these conditions. For this, we used a simple four-level dimensional categorization based on the severity of personality disturbance. The sample consisted of 352 patients admitted to mental health services. All underwent diagnostic assessments (SCID-I and SCID-II) and filled in questionnaires concerning their social situation and childhood adversities, and other validated tools, including the Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test (AUDIT), health-related quality of life (15D), and the five-item Mental Health Index (MHI-5). The patients were categorized into four groups according to the level of personality disturbance: 0 = No personality disturbance, 1 = Personality difficulty (one criterion less than threshold for one or more personality disorders), 2 = Simple personality disorder (one personality disorder), and 3 = Complex/Severe personality disorder (two or more personality disorders or any borderline and antisocial personality disorder). The proportions of the groups were as follows: no personality disturbance 38.4% (n = 135), personality difficulty 14.5% (n = 51), simple personality disorder 19.9% (n = 70), and complex/severe personality disorder 24.4% (n = 86). Patients with no personality disturbance were significantly differentiated (p < 0.05) from the other groups regarding the BDI, 15D, and MHI-5 scores as well as the number of Axis I diagnoses. Patients with complex/severe personality disorders stood out as being worst off. Social dysfunction was related to the severity of the personality disturbance. Patients with a personality difficulty or a simple personality disorder had prominent symptoms and difficulties, but the differences between these groups were mostly non-significant. An elevated severity level of personality disturbance is associated with an increase in psychiatric morbidity and social dysfunction. Diagnostically sub-threshold personality difficulties are of clinical significance and the degree of impairment corresponds to actual personality disorders. Since these two groups did not significantly differ from each other, our findings also highlight the complexity related to the use of diagnostic thresholds for separate personality disorders.

Dairy herd mastitis and reproduction: using simulation to aid interpretation of results from discrete time survival analysis.

PubMed

Hudson, Christopher D; Bradley, Andrew J; Breen, James E; Green, Martin J

2015-04-01

Probabilistic sensitivity analysis (PSA) is a simulation-based technique for evaluating the relative importance of different inputs to a complex process model. It is commonly employed in decision analysis and for evaluation of the potential impact of uncertainty in research findings on clinical practice, but has a wide variety of other possible applications. In this example, it was used to evaluate the association between herd-level udder health and reproductive performance in dairy herds. Although several recent studies have found relatively large associations between mastitis and fertility at the level of individual inseminations or lactations, the current study demonstrated that herd-level intramammary infection status is highly unlikely to have a clinically significant impact on the overall reproductive performance of a dairy herd under typical conditions. For example, a large increase in incidence rate of clinical mastitis (from 92 to 131 cases per 100 cows per year) would be expected to increase a herd's modified FERTEX score (a cost-based measure of overall reproductive performance) by just £4.50(1) per cow per year. The herd's background level of submission rate (proportion of eligible cows served every 21 days) and pregnancy risk (proportion of inseminations leading to a pregnancy) correlated strongly with overall reproductive performance and explained a large proportion of the between-herd variation in performance. PSA proved to be a highly useful technique to aid understanding of results from a complex statistical model, and has great potential for a wide variety of applications within the field of veterinary science. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.

PubMed

Simpson, J Steven A; Crawford, Susan G; Goldstein, Estelle T; Field, Catherine; Burgess, Ellen; Kaplan, Bonnie J

2011-04-18

Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment.

Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Molds of the Fusarium Genus

PubMed Central

Stubbe, Dirk; De Cremer, Koen; Piérard, Denis; Normand, Anne-Cécile; Piarroux, Renaud; Detandt, Monique; Hendrickx, Marijke

2014-01-01

The rates of infection with Fusarium molds are increasing, and a diverse number of Fusarium spp. belonging to different species complexes can cause infection. Conventional species identification in the clinical laboratory is time-consuming and prone to errors. We therefore evaluated whether matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a useful alternative. The 289 Fusarium strains from the Belgian Coordinated Collections of Microorganisms (BCCM)/Institute of Hygiene and Epidemiology Mycology (IHEM) culture collection with validated sequence-based identities and comprising 40 species were used in this study. An identification strategy was developed, applying a standardized MALDI-TOF MS assay and an in-house reference spectrum database. In vitro antifungal testing was performed to assess important differences in susceptibility between clinically relevant species/species complexes. We observed that no incorrect species complex identifications were made by MALDI-TOF MS, and 82.8% of the identifications were correct to the species level. This success rate was increased to 91% by lowering the cutoff for identification. Although the identification of the correct species complex member was not always guaranteed, antifungal susceptibility testing showed that discriminating between Fusarium species complexes can be important for treatment but is not necessarily required between members of a species complex. With this perspective, some Fusarium species complexes with closely related members can be considered as a whole, increasing the success rate of correct identifications to 97%. The application of our user-friendly MALDI-TOF MS identification approach resulted in a dramatic improvement in both time and accuracy compared to identification with the conventional method. A proof of principle of our MALDI-TOF MS approach in the clinical setting using recently isolated Fusarium strains demonstrated its validity. PMID:25411180

Another level of leadership: nurses on boards.

PubMed

Bleich, Michael R

2014-12-01

The movement to place nurses on boards of directors is growing, enriching boards with individuals possessing knowledge of clinical quality tied to care delivery models, human resource competencies and management, finance, and organizational change. Professional development educators are poised to advance a board's capacity to address complex health care problems.

Diabetes mellitus disease management in a safety net hospital system: translating evidence into practice.

PubMed

Butler, Michael K; Kaiser, Michael; Johnson, Jolene; Besse, Jay; Horswell, Ronald

2010-12-01

The Louisiana State University Health Care Services Division system assessed the effectiveness of implementing a multisite disease management program targeting diabetes mellitus in an indigent patient population. A population-based disease management program centered on evidence-based clinical care guidelines was applied from the system level. Specific clinic modifications and models were used, as well as ancillary services such as medication assistance and equipment subsidies. Marked improvement in process goals led to improved clinical outcomes. From 2001 to 2008, the percentage of patients with a hemoglobin A1c < 7.0 increased from 45% to 55% on the system level, with some sites experiencing a more dramatic shift. Results were similar across sites, which included both small provider groups and academic health centers. In order to achieve these results, the clinical environment changed to promote those evidence-based interventions. Even in complex environments such as academic health centers with several provider levels, or those environments with limited care resources, disease management programs can be successfully implemented and achieve statistically significant results.

Home Health Nurse Collaboration in the Medical Neighborhood of Children with Medical Complexity.

PubMed

Nageswaran, Savithri; Golden, Shannon L

2016-10-01

The objectives of this study were to describe how home healthcare nurses collaborate with other clinicians caring for children with medical complexity, and identify barriers to collaboration within the medical neighborhood. Using qualitative data obtained from 20 semistructured interviews (15 English, 5 Spanish) with primary caregivers of children with medical complexity and 18 home healthcare nurses, researchers inquired about experiences with home healthcare nursing services for these children. During an iterative analysis process, recurrent themes were identified by their prevalence and salience in the data. Home healthcare nurses collaborate with many providers within the medical neighborhood of children with medical complexity and perform many different collaborative tasks. This collaboration is valued by caregivers and nurses, but is inconsistent. Home healthcare nurses' communication with other clinicians is important to the delivery of good-quality care to children with medical complexity at home, but is not always present. Home healthcare nurses reported inability to share clinical information with other clinicians, not receiving child-specific information, and lack of support for clinical problem-solving as concerns. Barriers for optimal collaboration included lack of preparedness of parents, availability of physicians for clinical support, reimbursement for collaborative tasks, variability in home healthcare nurses' tasks, and problems at nursing agency level. Home healthcare nurses' collaboration with other clinicians is important, but problems exist in the current system of care. Optimizing collaboration between home healthcare nurses and other clinicians will likely have a positive impact on these children and their families.

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

PubMed

Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical nutrients on growth, lysis, spore formation, BoNT and TC production, and stability of BoNTs of C. botulinum We show that for C. botulinum ATCC 3502 cultured in a complex medium, a high level of arginine repressed BoNT expression by ca. 1,000-fold and also strongly reduced sporulation. Arginine stimulated growth and compensated for a lack of glucose. BoNT and toxin complex proteins were partially inactivated in a complex medium lacking glucose. This work should aid in optimizing BoNT production for pharmaceutical uses, and furthermore, an understanding of the nutritional regulation of growth and BoNT formation may provide insights into growth and BoNT formation in foods and clinical samples and into the enigmatic function of BoNTs in nature. Copyright © 2017 American Society for Microbiology.

Characterizing speech and language pathology outcomes in stroke rehabilitation.

PubMed

Hatfield, Brooke; Millet, Deborah; Coles, Janice; Gassaway, Julie; Conroy, Brendan; Smout, Randall J

2005-12-01

Hatfield B, Millet D, Coles J, Gassaway J, Conroy B, Smout RJ. Characterizing speech and language pathology outcomes in stroke rehabilitation. To describe a subset of speech-language pathology (SLP) patients in the Post-Stroke Rehabilitation Outcomes Project and to examine outcomes for patients with low admission FIM levels of auditory comprehension and verbal expression. Observational cohort study. Five inpatient rehabilitation hospitals. Patients (N=397) receiving post-stroke SLP with admission FIM cognitive components at levels 1 through 5. Not applicable. Increase in comprehension and expression FIM scores from admission to discharge. Cognitively and linguistically complex SLP activities (problem-solving and executive functioning skills) were associated with greater likelihood of success in low- to mid-level functioning communicators in the acute post-stroke rehabilitation period. The results challenge common clinical practice by suggesting that use of high-level cognitively and linguistically complex SLP activities early in a patient's stay may result in more efficient practice and better outcomes regardless of the patient's functional communication severity level on admission.

Biomarker Signatures of Mitochondrial NDUFS3 in Invasive Breast Carcinoma

PubMed Central

Suhane, Sonal; Berel, Dror; Ramanujan, V Krishnan

2011-01-01

We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma. PMID:21867691

Serological level of ICAM and ELAM adhesion molecules in allergic vascularitis.

PubMed

Alecu, M; Coman, G; Gălăţescu, E

1997-01-01

A 24-patient lot with hypersensitivity vasculitis was investigated for serological determinations of ICAM and ELAM adhesion molecules. Determinations were made in attack and in remission. Over two thirds of the cases presented elevated serological levels of ICAM and ELAM in attack, with twofold higher values than normal. In remission, in the absence of clinical signs, ICAM and ELAM values were normal in 19 cases (ICAM) and 22 cases (ELAM). Serological level of ICAM and ELAM was concordant with serological level of IL-2, IL-6, circulating immune complexes and clinical status. The increased values of ICAM and ELAM are due to the expression of these molecules both on the surface of endothelial cells and on immune cells. The adherence of leukocytes on the endothelial cells, by adhesion molecules involvement, followed by their extravasation represents an important event in the vascular lesion pathogeny of the hypersensitivity vasculitis.

Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the Cryptococcus Genus.

PubMed

Hagen, Ferry; Lumbsch, H Thorsten; Arsic Arsenijevic, Valentina; Badali, Hamid; Bertout, Sebastien; Billmyre, R Blake; Bragulat, M Rosa; Cabañes, F Javier; Carbia, Mauricio; Chakrabarti, Arunaloke; Chaturvedi, Sudha; Chaturvedi, Vishnu; Chen, Min; Chowdhary, Anuradha; Colom, Maria-Francisca; Cornely, Oliver A; Crous, Pedro W; Cuétara, Maria S; Diaz, Mara R; Espinel-Ingroff, Ana; Fakhim, Hamed; Falk, Rama; Fang, Wenjie; Herkert, Patricia F; Ferrer Rodríguez, Consuelo; Fraser, James A; Gené, Josepa; Guarro, Josep; Idnurm, Alexander; Illnait-Zaragozi, María-Teresa; Khan, Ziauddin; Khayhan, Kantarawee; Kolecka, Anna; Kurtzman, Cletus P; Lagrou, Katrien; Liao, Wanqing; Linares, Carlos; Meis, Jacques F; Nielsen, Kirsten; Nyazika, Tinashe K; Pan, Weihua; Pekmezovic, Marina; Polacheck, Itzhack; Posteraro, Brunella; de Queiroz Telles, Flavio; Romeo, Orazio; Sánchez, Manuel; Sampaio, Ana; Sanguinetti, Maurizio; Sriburee, Pojana; Sugita, Takashi; Taj-Aldeen, Saad J; Takashima, Masako; Taylor, John W; Theelen, Bart; Tomazin, Rok; Verweij, Paul E; Wahyuningsih, Retno; Wang, Ping; Boekhout, Teun

2017-01-01

Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within C. neoformans were raised to species level, and the same was done for five genotypes within C. gattii . In a recent perspective (K. J. Kwon-Chung et al., mSphere 2:e00357-16, 2017, https://doi.org/10.1128/mSphere.00357-16), it was argued that this taxonomic proposal was premature and without consensus in the community. Although the authors of the perspective recognized the existence of genetic diversity, they preferred the use of the informal nomenclature " C. neoformans species complex" and " C. gattii species complex." Here we highlight the advantage of recognizing these seven species, as ignoring these species will impede deciphering further biologically and clinically relevant differences between them, which may in turn delay future clinical advances.

A Complex Interplay: Cognitive Behavioural Therapy for Severe Health Anxiety in Addison's Disease to Reduce Emergency Department Admissions.

PubMed

Daniels, Jo; Sheils, Elizabeth

2017-07-01

Addison's disease (AD) is a rare chronic illness caused by adrenocortical insufficiency. Due to the pivotal role of the regulating hormone cortisol in AD, there is a common symptom overlap between the presentation of anxiety and adrenal crisis. Previous literature has identified the prevalence of anxiety in endocrinological disorders, however there is a paucity of research examining the complex interplay between AD and anxiety. This paper describes a single case study of a patient with severe health anxiety and co-morbid AD. The aims of the study were to establish if standard cognitive behavioural therapy for health anxiety in AD can lead to a reduction in psychological distress, and whether this approach is an effective intervention for the reduction of Emergency Department admissions. A single case design was used, with pre- and post-measures of health anxiety, general anxiety and depression. Data on Emergency Department admissions prior to and following treatment were used to assess change in this domain. Reliable and clinically significant reductions were seen across all measures, from severe to sub-clinical levels. There was a complete amelioration of Emergency Department admissions in the 12 months following completion of treatment. This preliminary study provides a sound rationale for further research into AD complicated by anxiety. Findings support the clinical utility of the cognitive behavioural therapy model for complex presentations of AD, offering a potential treatment option where anxiety is elevated and interfering with self-management and leading to high levels of health service use.

Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies.

PubMed

Lang, Bethan; Makuch, Mateusz; Moloney, Teresa; Dettmann, Inga; Mindorf, Swantje; Probst, Christian; Stoecker, Winfried; Buckley, Camilla; Newton, Charles R; Leite, M Isabel; Maddison, Paul; Komorowski, Lars; Adcock, Jane; Vincent, Angela; Waters, Patrick; Irani, Sarosh R

2017-04-01

Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin ( 125 I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125 I-αDTX and 125 I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125 I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical-serological correlations and a limited immunotherapy response. Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies. 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/.

Systemic estimation of the effect of photodynamic therapy of cancer

NASA Astrophysics Data System (ADS)

Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

1997-12-01

The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

Assessing reading levels of health information: uses and limitations of flesch formula.

PubMed

Jindal, Pranay; MacDermid, Joy C

2017-01-01

Written health information is commonly used by health-care professionals (HCPs) to inform and assess patients in clinical practice. With growing self-management of many health conditions and increased information seeking behavior among patients, there is a greater stress on HCPs and researchers to develop and implement readable and understandable health information. Readability formulas such as Flesch Reading Ease (FRE) and Flesch-Kincaid Reading Grade Level (FKRGL) are commonly used by researchers and HCPs to assess if health information is reading grade appropriate for patients. In this article, we critically analyze the role and credibility of Flesch formula in assessing the reading level of written health information. FRE and FKRGL assign a grade level by measuring semantic and syntactic difficulty. They serve as a simple tool that provides some information about the potential literacy difficulty of written health information. However, health information documents often involve complex medical words and may incorporate pictures and tables to improve the legibility. In their assessments, FRE and FKRGL do not take into account (1) document factors (layout, pictures and charts, color, font, spacing, legibility, and grammar), (2) person factors (education level, comprehension, health literacy, motivation, prior knowledge, information needs, anxiety levels), and (3) style of writing (cultural sensitivity, comprehensiveness, and appropriateness), and thus, inadequately assess reading level. New readability measures incorporate pictures and use complex algorithms to assess reading level but are only moderately used in health-care research and not in clinical practice. Future research needs to develop generic and disease-specific readability measures to evaluate comprehension of a written document based on individuals' literacy levels, cultural background, and knowledge of disease.

Impact of Remote Monitoring on Clinical Outcomes.

PubMed

Varma, Niraj; Ricci, Renato Pietro

2015-12-01

Follow-up of patients with cardiac implantable electronic devices is challenging due to both their increasing volume and technical complexity coupled to increasing clinical complexity of recipient patients. Remote monitoring (RM) offers an opportunity to resolve some of these difficulties by improving clinic efficiencies and providing a mechanism for device monitoring and patient management. Several recent randomized clinical trials and registries have demonstrated that RM may reduce in-hospital visit numbers, time required for patient follow-up, physician and nurse time, and hospital and social costs. Furthermore, patient retention and adherence to follow-up schedule are significantly improved by RM. Continuous wireless monitoring of data stored in the device memory with automatic alerts allows early detection of device malfunctions and of events, such as atrial fibrillation, ventricular arrhythmias, and heart failure suitable for clinical intervention. Early reaction may improve patient outcome. RM is easy to use and patients showed a high level of acceptance and satisfaction. Implementing RM in daily practice may require changes in clinic workflow. New organizational models promote significant efficiencies regarding physician and nursing time. Data management techniques are under development. Despite these demonstrable advantages of RM, adoption still remains modest, even in health care systems incentivized to use this follow-up method. © 2015 Wiley Periodicals, Inc.

Technological challenges of theranostics in oncology.

PubMed

Warenius, Hilmar M

2009-07-01

Although the term theranostics has been coined only fairly recently, attempts to relate the level of biomarkers to therapeutic response in the oncology clinic go back several decades. After a long period in which a limited number of individual theranostic molecular biomarkers gained general clinical acceptance, extremely powerful genomic and proteomic technologies have now emerged. These technologies, reviewed here, promise a potential revolution in our ability to predict therapeutic response in cancer, and by so doing, guide new anticancer drugs more successfully into clinical oncology practice. A full understanding of the detailed molecular nature of clinical cancer is, however, still evolving. The need for appropriate models of the highly complex disease, against which we are attempting to direct effective therapy more accurately, is also addressed. These should include an understanding of genomic and proteomic heterogeneity, genetic instability and systems biology models of cancer that take into account recent demonstrations of the vastly increased mutational state of the average clinical cancer as compared with the normal cell(s) from which it arose. The way forward in theranostics is, arguably, less dependent on further improvements in the already powerful genomic and proteomic technologies themselves than on our improved understanding of how we should apply them to the complex reality of the average clinical cancer.

Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease

PubMed Central

Rossi, Meghan; Mead, Simon; Collinge, John; Rudge, Peter; Vincent, Angela

2015-01-01

Objectives There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. Methods We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). Results Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. Conclusions This study indicates that <5% patients with sCJD develop serum antibodies to these neuronal antigens and, when positive, only at low titres. By contrast, three patients referred with possible prion disease had a clinical picture in keeping with autoimmune encephalitis and very high VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution. PMID:25246643

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health

PubMed Central

2011-01-01

Background Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. Methods All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. Results Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. Conclusions This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment. PMID:21501484

Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy.

PubMed

Satake, Kenji; Shimizu, Yoshio; Sasaki, Yohei; Yanagawa, Hiroyuki; Suzuki, Hitoshi; Suzuki, Yusuke; Horikoshi, Satoshi; Honda, Shinichiro; Shibuya, Kazuko; Shibuya, Akira; Tomino, Yasuhiko

2014-06-13

Although serum under-O-glycosylated IgA1 in IgA nephropathy (IgAN) patients may deposit more preferentially in glomeruli than heavily-O-glycosylated IgA1, the relationship between the glomerular IgA deposition level and the O-glycan profiles of serum IgA1 remains obscure. Serum total under-O-glycosylated IgA1 levels were quantified in 32 IgAN patients by an enzyme-linked immunosorbent assay (ELISA) with Helix aspersa (HAA) lectin. Serum under-O-glycosylated polymeric IgA1 (pIgA1) was selectively measured by an original method using mouse Fcα/μ receptor (mFcα/μR) transfectant and flow cytometry (pIgA1 trap). The percentage area of IgA deposition in the whole glomeruli (Area-IgA) was quantified by image analysis on the immunofluorescence of biopsy specimens. Correlations were assessed between the Area-IgA and data from HAA-ELISA or pIgA1 trap. The relationships between clinical parameters and data from HAA-ELISA or pIgA1 trap were analyzed by data mining approach. While the under-O-glycosylated IgA1 levels in IgAN patients were significantly higher than those in healthy controls when measured (p<0.05), there was no significant difference in under-O-glycosylated pIgA1. There was neither a correlation observed between the data from HAA-ELISA and pIgA1 trap (r2=0.09) in the IgAN patients (r2=0.005) nor was there a linear correlation between Area-IgA and data from HAA-ELISA or the pIgA1 trap (r2=0.005, 0.03, respectively). Contour plots of clinical parameters versus data from HAA-ELISA and the pIgA1 trap revealed that patients with a high score in each clinical parameter concentrated in specific areas, showing that patients with specific O-glycan profiles of IgA1 have similar clinical parameters. A decision tree analysis suggested that dominant immune complexes in glomeruli were consisted of: 1) IgA1-IgG and complements, 2) pIgA1 and complements, and 3) monomeric IgA1-IgA or aggregated monomeric IgA1. Serum under-O-glycosylated IgA1 levels are not correlated with glomerular IgA deposition based upon heterogeneity in the composition of glomerular immune complexes in IgAN patients.

Clinical strategies to aim an adequate safety profile for patients and effective training for surgical residents: The laparoscopic cholecystectomy model.

PubMed

Bresadola, Vittorio; Pravisani, Riccardo; Pighin, Marina; Seriau, Luca; Cherchi, Vittorio; Giuseppe, Sergio; Risaliti, Andrea

2016-11-01

Training programs for resident surgeons represent a challenge for the mentoring activity. The aim of the present study is to investigate the impact of our training program for laparoscopic cholecystectomy on patient's safety and on the modulation of the residents' exposure to clinical scenario with different grades of complexity. This is a retrospective study based on a clinical series of laparoscopic cholecystectomy performed in a teaching hospital. Study population was grouped according to the expertise of the attending primary operator among resident surgeons. Four groups were identified: consultant (C), senior resident (SR); intermediate level resident (IR); junior resident (JR). The intraoperative and postoperative outcomes were confronted to evaluate the patient's safety profile. 447 patients were submitted to LC: 96 cases were operated by a C, 200 by SR, 112 by IR and 39 by JR. The mean operative time was the longest for the JR group. A statistically higher rate of conversion to open approach was registered in C and IR groups in comparison to JR and SR groups. However, in C and IR groups, patients had worse ASA score, higher BMI and more frequent past history of previous abdominal surgery, cholecystitis or pancreatitis. Overall, it was not registered any statistically significant difference among the groups in terms of length of hospital stay and prevalence of major postoperative complications. Applying an educational model based on both graduated levels of responsibility and modulated grade of clinical complexity can guarantee an high safety profile.

The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

PubMed Central

Esserman, Denise; Allore, Heather G.; Travison, Thomas G.

2016-01-01

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters. PMID:27478520

A report from a single institute's 14-year experience in treatment of male-to-female transsexuals.

PubMed

Imbimbo, Ciro; Verze, Paolo; Palmieri, Alessandro; Longo, Nicola; Fusco, Ferdinando; Arcaniolo, Davide; Mirone, Vincenzo

2009-10-01

Gender identity disorder or transsexualism is a complex clinical condition, and prevailing social context strongly impacts the form of its manifestations. Sex reassignment surgery (SRS) is the crucial step of a long and complex therapeutic process starting with preliminary psychiatric evaluation and culminating in definitive gender identity conversion. The aim of our study is to arrive at a clinical and psychosocial profile of male-to-female transsexuals in Italy through analysis of their personal and clinical experience and evaluation of their postsurgical satisfaction levels SRS. From January 1992 to September 2006, 163 male patients who had undergone gender-transforming surgery at our institution were requested to complete a patient satisfaction questionnaire. The questionnaire consisted of 38 questions covering nine main topics: general data, employment status, family status, personal relationships, social and cultural aspects, presurgical preparation, surgical procedure, and postsurgical sex life and overall satisfaction. Average age was 31 years old. Seventy-two percent had a high educational level, and 63% were steadily employed. Half of the patients had contemplated suicide at some time in their lives before surgery and 4% had actually attempted suicide. Family and colleague emotional support levels were satisfactory. All patients had been adequately informed of surgical procedure beforehand. Eighty-nine percent engaged in postsurgical sexual activities. Seventy-five percent had a more satisfactory sex life after SRS, with main complications being pain during intercourse and lack of lubrication. Seventy-eight percent were satisfied with their neovagina's esthetic appearance, whereas only 56% were satisfied with depth. Almost all of the patients were satisfied with their new sexual status and expressed no regrets. Our patients' high level of satisfaction was due to a combination of a well-conducted preoperative preparation program, competent surgical skills, and consistent postoperative follow-up.

Working memory, reasoning, and expertise in medicine-insights into their relationship using functional neuroimaging.

PubMed

Hruska, Pam; Krigolson, Olav; Coderre, Sylvain; McLaughlin, Kevin; Cortese, Filomeno; Doig, Christopher; Beran, Tanya; Wright, Bruce; Hecker, Kent G

2016-12-01

Clinical reasoning is dependent upon working memory (WM). More precisely, during the clinical reasoning process stored information within long-term memory is brought into WM to facilitate the internal deliberation that affords a clinician the ability to reason through a case. In the present study, we examined the relationship between clinical reasoning and WM while participants read clinical cases with functional magnetic resonance imaging (fMRI). More specifically, we examined the impact of clinical case difficulty (easy, hard) and clinician level of expertise (2nd year medical students, senior gastroenterologists) on neural activity within regions of cortex associated with WM (i.e., the prefrontal cortex) during the reasoning process. fMRI was used to scan ten second-year medical students and ten practicing gastroenterologists while they reasoned through sixteen clinical cases [eight straight forward (easy) and eight complex (hard)] during a single 1-h scanning session. Within-group analyses contrasted the easy and hard cases which were then subsequently utilized for a between-group analysis to examine effects of expertise (novice > expert, expert > novice). Reading clinical cases evoked multiple neural activations in occipital, prefrontal, parietal, and temporal cortical regions in both groups. Importantly, increased activation in the prefrontal cortex in novices for both easy and hard clinical cases suggests novices utilize WM more so than experts during clinical reasoning. We found that clinician level of expertise elicited differential activation of regions of the human prefrontal cortex associated with WM during clinical reasoning. This suggests there is an important relationship between clinical reasoning and human WM. As such, we suggest future models of clinical reasoning take into account that the use of WM is not consistent throughout all clinical reasoning tasks, and that memory structure may be utilized differently based on level of expertise.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

PubMed

Powers, Jacquelyn M; Buchanan, George R; Adix, Leah; Zhang, Song; Gao, Ang; McCavit, Timothy L

2017-06-13

Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 μg/dL (ferrous sulfate) vs 506 to 417 μg/dL (iron complex) (a greater difference of -50 μg/dL [95% CI, -86 to -14 μg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04). Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia. clinicaltrials.gov Identifier: NCT01904864.

A Quantitative Systems Pharmacology Approach to Infer Pathways Involved in Complex Disease Phenotypes.

PubMed

Schurdak, Mark E; Pei, Fen; Lezon, Timothy R; Carlisle, Diane; Friedlander, Robert; Taylor, D Lansing; Stern, Andrew M

2018-01-01

Designing effective therapeutic strategies for complex diseases such as cancer and neurodegeneration that involve tissue context-specific interactions among multiple gene products presents a major challenge for precision medicine. Safe and selective pharmacological modulation of individual molecular entities associated with a disease often fails to provide efficacy in the clinic. Thus, development of optimized therapeutic strategies for individual patients with complex diseases requires a more comprehensive, systems-level understanding of disease progression. Quantitative systems pharmacology (QSP) is an approach to drug discovery that integrates computational and experimental methods to understand the molecular pathogenesis of a disease at the systems level more completely. Described here is the chemogenomic component of QSP for the inference of biological pathways involved in the modulation of the disease phenotype. The approach involves testing sets of compounds of diverse mechanisms of action in a disease-relevant phenotypic assay, and using the mechanistic information known for the active compounds, to infer pathways and networks associated with the phenotype. The example used here is for monogenic Huntington's disease (HD), which due to the pleiotropic nature of the mutant phenotype has a complex pathogenesis. The overall approach, however, is applicable to any complex disease.

Acknowledging and allocating responsibility for clinical inertia in the management of Type 2 diabetes in primary care: a qualitative study.

PubMed

Zafar, A; Stone, M A; Davies, M J; Khunti, K

2015-03-01

Failure to intensify treatment in patients with Type 2 diabetes with suboptimal blood glucose control has been termed clinical inertia and has been shown to contribute to poorer patient outcomes. We aimed to identify and explore perceptions about clinical inertia from the perspective of primary healthcare providers. A qualitative study was conducted in Leicestershire and Northamptonshire, UK. Purposive sampling was based on healthcare providers working in primary care settings with 'higher' and 'lower' target achievement based on routine data. Twenty semi-structured interviews were conducted, face-to-face or by telephone. Thematic analysis was informed by the constant comparative approach. An important broad theme that emerged during the analysis was related to attribution and explanation of responsibility for clinical inertia. This included general willingness to accept a degree of responsibility for clinical inertia. In some cases, however, participants had inaccurate perceptions about levels of target achievement in their primary care centres, as indicated by routine data. Participants sought to lessen their own sense of accountability by highlighting patient-level barriers such as comorbidities and human fallibility, and also system-level barriers, particularly time constraints. Perceptions about ways of addressing the problem of clinical inertia were not seen as straightforward, further emphasizing a complex and cumulative pattern of barriers. In order to understand and address the problem of clinical inertia, provider, patient- and system-level barriers should be considered together rather than as separate issues. Acknowledgement of responsibility should be regarded positively as a motivator for change. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Voluntariness of consent to HIV clinical research: A conceptual and empirical pilot study.

PubMed

Mamotte, Nicole; Wassenaar, Douglas

2017-09-01

Obtaining voluntary informed consent for research participation is an ethical imperative, yet there appears to be little consensus regarding what constitutes a voluntary consent decision. An instrument to assess influences on participants' consent decision and perceived voluntariness was developed and piloted in two South African HIV clinical trials. The pilot study found high levels of perceived voluntariness. The feeling of having no choice but to participate was significantly associated with lower perceived voluntariness. Overall the data suggest that it is possible to obtain voluntary and valid consent for research participants in ethically complex HIV clinical trials in a developing country context.

A visual approach to providing prognostic information to parents of children with retinoblastoma.

PubMed

Panton, Rachel L; Downie, Robert; Truong, Tran; Mackeen, Leslie; Kabene, Stefane; Yi, Qi-Long; Chan, Helen S L; Gallie, Brenda L

2009-03-01

Parents must rapidly assimilate complex information when a child is diagnosed with cancer. Education correlates with the ability to process and use medical information. Graphic tools aid reasoning and communicate complex ideas with precision and efficiency. We developed a graphic tool, DePICT (Disease-specific electronic Patient Illustrated Clinical Timeline), to visually display entire retinoblastoma treatment courses from real-time clinical data. We report retrospective evaluation of the effectiveness of DePICT to communicate risk and complexity of treatment to parents. We assembled DePICT graphics from multiple children on cards representing each stage of intraocular retinoblastoma. Forty-four parents completed a 14-item questionnaire to evaluate the understanding of retinoblastoma treatment and outcomes acquired from DePICT. As a proposed tool for informed consent, DePICT effectively communicated knowledge of complex medical treatment and risks, regardless of the education level. We identified multiple potential factors affecting parent comprehension of treatment complexity and risk. These include language proficiency (p=0.005) and age-related experience, as younger parents had higher education (p=0.021) but lower comprehension scores (p=0.011), regardless of first language. Provision of information at diagnosis concerning long-term treatment complexity helps parents of children with cancer. DePICT effectively transfers knowledge of treatments, risks, and prognosis in a manner that offsets parental educational disadvantages.

Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach

PubMed Central

Shahab, Shubin W.; Matyunina, Lilya V.; Mezencev, Roman; Walker, L. DeEtte; Bowen, Nathan J.; Benigno, Benedict B.; McDonald, John F.

2011-01-01

MicroRNAs (miRNAs) are short (∼22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ∼11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs in vivo is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs in vivo. Our findings underscore the complexities of miRNA-mediated regulation in vivo and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized. PMID:21811625

Serum neutrophil gelatinase-associated lipocalin levels are correlated with the complexity and the severity of atherosclerosis in acute coronary syndrome

PubMed Central

Soylu, Korhan; Aksan, Gökhan; Nar, Gökay; Özdemir, Metin; Gülel, Okan; İnci, Sinan; Aksakal, Aytekin; İdil Soylu, Ayşegül; Yılmaz, Özcan

2015-01-01

Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is a novel inflammatory marker that is released from neutrophils. In this study, we evaluated the correlation between serum NGAL level and clinical and angiographic risk scores in patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: Forty-seven random NSTE-ACS patients and 45 patients with normal coronary arteries (NCA) who underwent coronary angiography were enrolled in the study. GRACE risk score and SYNTAX and Gensini risk scores were used, respectively, for the purpose of clinical risk assessment and angiographic risk scoring. Serum NGAL level was measured via ELISA in peripheral blood samples obtained from the patients at the time of admission. Results: Serum NGAL level was significantly higher in the NSTE-ACS group compared to the control group (112.3±49.6 ng/mL vs. 58.1±24.3 ng/mL, p<0.001). There was a significant positive correlation between serum NGAL levels and the GRACE (r=0.533 and p<0.001), SYNTAX (r=0.395 and p=0.006), and Gensini risk scores (r=0.575 and p<0.001). The intermediate-high SYNTAX (>22) group had statistically significantly higher serum NGAL levels compared to the low SYNTAX (≤22) group (143±29.5 ng/mL vs. 98.7±43.2 ng/mL, p=0.001). Conclusion: NGAL level was positively correlated with lesion complexity and severity of coronary artery disease in patients with NSTE-ACS. Serum NGAL levels on admission are associated with increased burden of atherosclerosis in patients with NSTE-ACS. PMID:25430410

P-value interpretation and alpha allocation in clinical trials.

PubMed

Moyé, L A

1998-08-01

Although much value has been placed on type I error event probabilities in clinical trials, interpretive difficulties often arise that are directly related to clinical trial complexity. Deviations of the trial execution from its protocol, the presence of multiple treatment arms, and the inclusion of multiple end points complicate the interpretation of an experiment's reported alpha level. The purpose of this manuscript is to formulate the discussion of P values (and power for studies showing no significant differences) on the basis of the event whose relative frequency they represent. Experimental discordance (discrepancies between the protocol's directives and the experiment's execution) is linked to difficulty in alpha and beta interpretation. Mild experimental discordance leads to an acceptable adjustment for alpha or beta, while severe discordance results in their corruption. Finally, guidelines are provided for allocating type I error among a collection of end points in a prospectively designed, randomized controlled clinical trial. When considering secondary end point inclusion in clinical trials, investigators should increase the sample size to preserve the type I error rates at acceptable levels.

Advancing clinical reasoning in virtual patients - development and application of a conceptual framework.

PubMed

Hege, Inga; Kononowicz, Andrzej A; Berman, Norman B; Lenzer, Benedikt; Kiesewetter, Jan

2018-01-01

Background: Clinical reasoning is a complex skill students have to acquire during their education. For educators it is difficult to explain their reasoning to students, because it is partly an automatic and unconscious process. Virtual Patients (VPs) are used to support the acquisition of clinical reasoning skills in healthcare education. However, until now it remains unclear which features or settings of VPs optimally foster clinical reasoning. Therefore, our aims were to identify key concepts of the clinical reasoning process in a qualitative approach and draw conclusions on how each concept can be enhanced to advance the learning of clinical reasoning with virtual patients. Methods: We chose a grounded theory approach to identify key categories and concepts of learning clinical reasoning and develop a framework. Throughout this process, the emerging codes were discussed with a panel of interdisciplinary experts. In a second step we applied the framework to virtual patients. Results: Based on the data we identified the core category as the "multifactorial nature of learning clinical reasoning". This category is reflected in the following five main categories: Psychological Theories, Patient-centeredness, Context, Learner-centeredness, and Teaching/Assessment. Each category encompasses between four and six related concepts. Conclusions: With our approach we were able to elaborate how key categories and concepts of clinical reasoning can be applied to virtual patients. This includes aspects such as allowing learners to access a large number of VPs with adaptable levels of complexity and feedback or emphasizing dual processing, errors, and uncertainty.

Advancing clinical reasoning in virtual patients – development and application of a conceptual framework

PubMed Central

Hege, Inga; Kononowicz, Andrzej A.; Berman, Norman B.; Lenzer, Benedikt; Kiesewetter, Jan

2018-01-01

Background: Clinical reasoning is a complex skill students have to acquire during their education. For educators it is difficult to explain their reasoning to students, because it is partly an automatic and unconscious process. Virtual Patients (VPs) are used to support the acquisition of clinical reasoning skills in healthcare education. However, until now it remains unclear which features or settings of VPs optimally foster clinical reasoning. Therefore, our aims were to identify key concepts of the clinical reasoning process in a qualitative approach and draw conclusions on how each concept can be enhanced to advance the learning of clinical reasoning with virtual patients. Methods: We chose a grounded theory approach to identify key categories and concepts of learning clinical reasoning and develop a framework. Throughout this process, the emerging codes were discussed with a panel of interdisciplinary experts. In a second step we applied the framework to virtual patients. Results: Based on the data we identified the core category as the "multifactorial nature of learning clinical reasoning". This category is reflected in the following five main categories: Psychological Theories, Patient-centeredness, Context, Learner-centeredness, and Teaching/Assessment. Each category encompasses between four and six related concepts. Conclusions: With our approach we were able to elaborate how key categories and concepts of clinical reasoning can be applied to virtual patients. This includes aspects such as allowing learners to access a large number of VPs with adaptable levels of complexity and feedback or emphasizing dual processing, errors, and uncertainty. PMID:29497697

Omega-3 fatty acids: new insights into the pharmacology and biology of docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid.

PubMed

Davidson, Michael H

2013-12-01

Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review. FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles. Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.

42 CFR 493.1415 - Condition: Laboratories performing moderate complexity testing; clinical consultant.

Code of Federal Regulations, 2010 CFR

2010-10-01

... complexity testing; clinical consultant. 493.1415 Section 493.1415 Public Health CENTERS FOR MEDICARE... § 493.1415 Condition: Laboratories performing moderate complexity testing; clinical consultant. The laboratory must have a clinical consultant who meets the qualification requirements of § 493.1417 of this...

Predictors of treatment efficacy in a clinical trial of three psychosocial treatments for adolescent depression.

PubMed

Brent, D A; Kolko, D J; Birmaher, B; Baugher, M; Bridge, J; Roth, C; Holder, D

1998-09-01

To assess the predictors of treatment outcome across treatments, as well as those associated with differential treatment response. One hundred seven adolescent outpatients, aged 13 to 18 years, with DSM-III-R major depression were randomly assigned to one of three manual-based, brief (12 to 16 sessions) psychosocial treatments: cognitive-behavioral therapy (CBT), systemic-behavioral family therapy, or nondirective supportive therapy. Those with good and poor outcomes were compared. Continued depression was predicted by clinical referral (versus via advertisement) and was in part mediated by hopelessness. Other predictors of depression were comorbid anxiety disorder and higher levels of cognitive distortion and hopelessness at intake. Achievement of clinical remission was predicted by a higher level of self-reported depression. Poorer functional status was predicted by a higher level of initial interviewer-rated depression. Comorbid anxiety and maternal depressive symptoms predicted differential treatment efficacy. CBT's performance continued to be robust with respect to nondirective supportive therapy, even in the presence of the above-noted adverse predictors. Predictors of poor outcome may give clues as to how to boost treatment response. Subjects who come to treatment for clinical trials via advertisement (versus clinical referral) may show more favorable treatment responses. CBT is likely to be a robust intervention even in more complex and difficult-to-treat patients.

Effective feedback strategies for teaching in pediatric and adolescent gynecology.

PubMed

Kaul, Paritosh; Gong, Jennifer; Guiton, Gretchen

2014-08-01

The clinical setting of pediatric and adolescent gynecology poses complex tasks for the physician with its numerous procedures and the communication demands of interacting with an adolescent and/or guardian. Needless to say, teaching within this setting is highly demanding. Regardless of the level of learner or the professional role (e.g., nurse, medical student, resident, physician assistant) represented, clinical teaching requires that the instructor provide feedback in ways that benefit the student. Recent research on feedback suggests a more complex understanding of feedback than in the past. This article highlights key research and its implication for effective feedback by presenting a three part framework; know your learner, understand what is to be learned, and plan for improvement. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Predictive model of complexity in early palliative care: a cohort of advanced cancer patients (PALCOM study).

PubMed

Tuca, Albert; Gómez-Martínez, Mónica; Prat, Aleix

2018-01-01

Model of early palliative care (PC) integrated in oncology is based on shared care from the diagnosis to the end of life and is mainly focused on patients with greater complexity. However, there is no definition or tools to evaluate PC complexity. The objectives of the study were to identify the factors influencing level determination of complexity, propose predictive models, and build a complexity scale of PC. We performed a prospective, observational, multicenter study in a cohort of advanced cancer patients with an estimated prognosis ≤ 6 months. An ad hoc structured evaluation including socio-demographic and clinical data, symptom burden, functional and cognitive status, psychosocial problems, and existential-ethic dilemmas was recorded systematically. According to this multidimensional evaluation, investigator classified patients as high, medium, or low palliative complexity, associated to need of basic or specialized PC. Logistic regression was used to identify the variables influencing determination of level of PC complexity and explore predictive models. We included 324 patients; 41% were classified as having high PC complexity and 42.9% as medium, both levels being associated with specialized PC. Variables influencing determination of PC complexity were as follows: high symptom burden (OR 3.19 95%CI: 1.72-6.17), difficult pain (OR 2.81 95%CI:1.64-4.9), functional status (OR 0.99 95%CI:0.98-0.9), and social-ethical existential risk factors (OR 3.11 95%CI:1.73-5.77). Logistic analysis of variables allowed construct a complexity model and structured scales (PALCOM 1 and 2) with high predictive value (AUC ROC 76%). This study provides a new model and tools to assess complexity in palliative care, which may be very useful to manage referral to specialized PC services, and agree intensity of their intervention in a model of early-shared care integrated in oncology.

Revisioning Clinical Psychology: Integrating Cultural Psychology into Clinical Research and Practice with Portuguese Immigrants

PubMed Central

James, Susan; Harris, Sara; Foster, Gary; Clarke, Juanne; Gadermann, Anne; Morrison, Marie; Bezanson, Birdie Jane

2013-01-01

This article outlines a model for conducting psychotherapy with people of diverse cultural backgrounds. The theoretical foundation for the model is based on clinical and cultural psychology. Cultural psychology integrates psychology and anthropology in order to provide a complex understanding of both culture and the individual within his or her cultural context. The model proposed in this article is also based on our clinical experience and mixed-method research with the Portuguese community. The model demonstrates its value with ethnic minority clients by situating the clients within the context of their multi-layered social reality. The individual, familial, socio-cultural, and religio-moral domains are explored in two research projects, revealing the interrelation of these levels/contexts. The article is structured according to these domains. Study 1 is a quantitative study that validates the Agonias Questionnaire in Ontario. The results of this study are used to illustrate the individual domain of our proposed model. Study 2 is an ethnography conducted in the Azorean Islands, and the results of this study are integrated to illustrate the other three levels of the model, namely family, socio-cultural, and the religio-moral levels. PMID:23720642

The effect of preparation strategies, qualification and professional background on clinical nurse educator confidence.

PubMed

Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

2018-06-12

To describe how clinical nurse educators in Vietnam are prepared for their role; to identify which preparation strategies assist development of confidence in clinical teaching; and to measure the effect of educational qualifications and professional background on perceived confidence levels. The quality of clinical teaching can directly affect the quality of the student learning experience. The role of the clinical educator is complex and dynamic and requires a period of adjustment for successful role transition to occur. Planned orientation and specific preparation programs assist transition and reduce anxiety for new clinical nurse educators. There is, however, a lack of clear evidence to identify the form this preparation should take or which strategies are likely to facilitate the development of role confidence. Descriptive survey study. Cross-sectional surveys were used to collect data from 334 clinical nurse educators during January - March 2015. Eight preparation methods commonly used in Vietnam were identified. There was a small yet significant association between preparation and clinical nurse educators' perceived confidence. Formal preparation methods, as well as postgraduate qualifications and years of clinical teaching experience were linked to increased confidence in clinical teaching. Conversely, informal mentorship was found to hinder confidence development. This study identifies several preparation strategies that significantly enhance clinical educator confidence and readiness for their complex role. These preparation strategies drawn from the Vietnamese context, provide important examples for the wider nursing community to consider. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The use of adjustable gastric bands for management of severe and complex obesity

PubMed Central

Hopkins, James C. A.; Blazeby, Jane M.; Rogers, Chris A.; Welbourn, Richard

2016-01-01

Background Obesity levels in the UK have reached a sustained high and ∼4% of the population would be candidates for bariatric surgery based upon current UK NICE guidelines, which has important implications for Clinical Commissioning Groups. Sources of data Summary data from Cochrane systematic reviews, randomized controlled trials (RCTs) and cohort studies. Areas of agreement Currently, the only treatment that offers significant and durable weight loss for those with severe and complex obesity is surgery. Three operations account for 95% of all bariatric surgery in the UK, but the NHS offers surgery to only a small fraction of those who could benefit. Laparoscopic adjustable gastric banding (gastric banding) has potentially the lowest risk and up-front costs of the three procedures. Areas of controversy Reliable Level 1 evidence of the relative effectiveness of the operations is lacking. Growing points As a point intervention, weight loss surgery together with the chronic disease management strategy for obesity can prevent significant future disease and mortality, and the NHS should embrace both. Areas timely for developing research Better RCT evidence is needed including clinical effectiveness and economic analysis to answer the important question ‘which is the best of the three operations most frequently performed?’ This review considers the current evidence for gastric banding for the treatment of severe and complex obesity. PMID:27034443

Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.

PubMed

Matsumura, Y; Nishigori, C; Yagi, T; Imamura, S; Takebe, H

1998-06-01

Xeroderma pigmentosum (XP) complementation group F was first reported in Japan and most XP-F patients reported to date are Japanese. The clinical features of XP-F patients are rather mild, including late onset of skin cancer. Recently a cDNA that corrects the repair deficiency of cultured XP-F cells was isolated. The XPF protein forms a tight complex with ERCC1 and this complex functions as a structure-specific endonuclease responsible for the 5' incision during DNA excision repair. Here we have identified XPF mRNA mutations and examined levels of the mRNA and protein expression in seven primary cell strains from Japanese XP-F patients. The XP-F cell strains were classified into three types in terms of the effect of the mutation on the predicted protein; (i) XPF proteins with amino acid substitutions; (ii) amino acid substituted and truncated XPF proteins; and (iii) truncated XPF protein only. A normal level of expression of XPF mRNA was observed in XP-F cells but XPF protein was extremely low. These results indicate that the detected mutations lead to unstable XPF protein, resulting in a decrease in formation of the ERCC1-XPF endonuclease complex. Slow excision repair of UV-induced DNA damage due to low residual endonuclease activity provides a plausible explanation for the typical mild phenotype of XP-F patients.

Simplifying the complexity surrounding ICU work processes--identifying the scope for information management in ICU settings.

PubMed

Munir, Samina K; Kay, Stephen

2005-08-01

A multi-site study, conducted in two English and two Danish intensive care units, investigates the complexity of work processes in intensive care, and the implications of this complexity for information management with regards to clinical information systems. Data were collected via observations, shadowing of clinical staff, interviews and questionnaires. The construction of role activity diagrams enabled the capture of critical care work processes. Upon analysing these diagrams, it was found that intensive care work processes consist of 'simplified-complexity', these processes are changed with the introduction of information systems for the everyday use and management of all clinical information. The prevailing notion of complexity surrounding critical care clinical work processes was refuted and found to be misleading; in reality, it is not the work processes that cause the complexity, the complexity is rooted in the way in which clinical information is used and managed. This study emphasises that the potential for clinical information systems that consider integrating all clinical information requirements is not only immense but also very plausible.

Interprofessional collaboration in research, education, and clinical practice: working together for a better future.

PubMed

Green, Bart N; Johnson, Claire D

2015-03-01

Interprofessional collaboration occurs when 2 or more professions work together to achieve common goals and is often used as a means for solving a variety of problems and complex issues. The benefits of collaboration allow participants to achieve together more than they can individually, serve larger groups of people, and grow on individual and organizational levels. This editorial provides an overview of interprofessional collaboration in the areas of clinical practice, education, and research; discusses barriers to collaboration; and suggests potential means to overcome them.

Direct care registered nurses' and nursing leaders' review of the clinical competencies needed for the successful nurse of the future: a gap analysis.

PubMed

Strong, Margaret; Kane, Irene; Petras, Denise; Johnson-Joy, Cheryl; Weingarten, Joseph

2014-01-01

Direct care nurses and nurse leaders were surveyed on their perceptions of the appropriateness, importance, and use in daily practice of 10 clinical nursing competencies needed for nurses to be successful in the future. Competencies needed in the 21st century are not based entirely on task-driven motor skills because comprehensive knowledge is essential to care for complex patients. Differences identified between direct care nurses, leaders, and educational levels provide educational opportunities for both groups.

[Clinic of environmental pediatric care in a high complexity hospital].

PubMed

Gaioli, Marisa; Amoedo, Diego; González, Daniel

2014-12-01

Children environmental health is considered by The World Health Organization as one of the main challenges of Public Health during the Century XXI. They promote the development of programs that allow approaching, disclosure or mitigation of the impact of polluting agents on health at every level of pediatric attention. The Children Hospital "Prof. Dr. Juan P. Garrahan" has created an Environmental Health Office in order to address the demands of those patients with suspected or verified exposure to environmental risks. An Environmental Clinical History has been elaborated with this purpose.

Interprofessional collaboration in research, education, and clinical practice: working together for a better future

PubMed Central

Green, Bart N.; Johnson, Claire D.

2015-01-01

Interprofessional collaboration occurs when 2 or more professions work together to achieve common goals and is often used as a means for solving a variety of problems and complex issues. The benefits of collaboration allow participants to achieve together more than they can individually, serve larger groups of people, and grow on individual and organizational levels. This editorial provides an overview of interprofessional collaboration in the areas of clinical practice, education, and research; discusses barriers to collaboration; and suggests potential means to overcome them. PMID:25594446

Emergency Department Patients Support the Use of Combat Medics in Their Clinical Care

DTIC Science & Technology

2015-07-01

indirect supervision is the growing complexity of modern medi- cine . If this level of supervised and controlled training is required of aviation and...readiness of brigade combat teams fighting the Global War on Terror . J Surg Res. 2007;138:25–31. 4. Mabry RL, Apodaca A, Penrod J, et al. Impact of

Spanish Guidelines for Management of Chronic Obstructive Pulmonary Disease (GesEPOC) 2017. Pharmacological Treatment of Stable Phase.

PubMed

Miravitlles, Marc; Soler-Cataluña, Juan José; Calle, Myriam; Molina, Jesús; Almagro, Pere; Quintano, José Antonio; Trigueros, Juan Antonio; Cosío, Borja G; Casanova, Ciro; Antonio Riesco, Juan; Simonet, Pere; Rigau, David; Soriano, Joan B; Ancochea, Julio

2017-06-01

The clinical presentation of chronic obstructive pulmonary disease (COPD) varies widely, so treatment must be tailored according to the level of risk and phenotype. In 2012, the Spanish COPD Guidelines (GesEPOC) first established pharmacological treatment regimens based on clinical phenotypes. These regimens were subsequently adopted by other national guidelines, and since then, have been backed up by new evidence. In this 2017 update, the original severity classification has been replaced by a much simpler risk classification (low or high risk), on the basis of lung function, dyspnea grade, and history of exacerbations, while determination of clinical phenotype is recommended only in high-risk patients. The same clinical phenotypes have been maintained: non-exacerbator, asthma-COPD overlap (ACO), exacerbator with emphysema, and exacerbator with bronchitis. Pharmacological treatment of COPD is based on bronchodilators, the only treatment recommended in low-risk patients. High-risk patients will receive different drugs in addition to bronchodilators, depending on their clinical phenotype. GesEPOC reflects a more individualized approach to COPD treatment, according to patient clinical characteristics and level of risk or complexity. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Ethical and social implications of genetic testing for communication disorders.

PubMed

Arnos, Kathleen S

2008-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests.

Ethical and social implications of genetic testing for communication disorders

PubMed Central

Arnos, Kathleen S.

2013-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. Learning outcomes As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests. PMID:18452941

Correlations Between Clinical Judgement and Learning Style Preferences of Nursing Students in the Simulation Room.

PubMed

Hallin, Karin; Haggstrom, Marie; Backstrom, Britt; Kristiansen, Lisbeth Porskrog

2015-09-28

Health care educators account for variables affecting patient safety and are responsible for developing the highly complex process of education planning. Clinical judgement is a multidimensional process, which may be affected by learning styles. The aim was to explore three specific hypotheses to test correlations between nursing students' team achievements in clinical judgement and emotional, sociological and physiological learning style preferences. A descriptive cross-sectional study was conducted with Swedish university nursing students in 2012-2013. Convenience sampling was used with 60 teams with 173 nursing students in the final semester of a three-year Bachelor of Science in nursing programme. Data collection included questionnaires of personal characteristics, learning style preferences, determined by the Dunn and Dunn Productivity Environmental Preference Survey, and videotaped complex nursing simulation scenarios. Comparison with Lasater Clinical Judgement Rubric and Non-parametric analyses were performed. Three significant correlations were found between the team achievements and the students' learning style preferences: significant negative correlation with 'Structure' and 'Kinesthetic' at the individual level, and positive correlation with the 'Tactile' variable. No significant correlations with students' 'Motivation', 'Persistence', 'Wish to learn alone' and 'Wish for an authoritative person present' were seen. There were multiple complex interactions between the tested learning style preferences and the team achievements of clinical judgement in the simulation room, which provides important information for the becoming nurses. Several factors may have influenced the results that should be acknowledged when designing further research. We suggest conducting mixed methods to determine further relationships between team achievements, learning style preferences, cognitive learning outcomes and group processes.

Drugs' development in acute heart failure: what went wrong?

PubMed

Teneggi, Vincenzo; Sivakumar, Nithy; Chen, Deborah; Matter, Alex

2018-05-08

Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.

Tafenoquine, an Antiplasmodial 8-Aminoquinoline, Targets Leishmania Respiratory Complex III and Induces Apoptosis ▿

PubMed Central

Carvalho, Luis; Luque-Ortega, Juan Román; Manzano, José Ignacio; Castanys, Santiago; Rivas, Luis; Gamarro, Francisco

2010-01-01

Tafenoquine (TFQ), an 8-aminoquinoline analogue of primaquine, which is currently under clinical trial (phase IIb/III) for the treatment and prevention of malaria, may represent an alternative treatment for leishmaniasis. In this work, we have studied the mechanism of action of TFQ against Leishmania parasites. TFQ impaired the overall bioenergetic metabolism of Leishmania promastigotes, causing a rapid drop in intracellular ATP levels without affecting plasma membrane permeability. TFQ induced mitochondrial dysfunction through the inhibition of cytochrome c reductase (respiratory complex III) with a decrease in the oxygen consumption rate and depolarization of mitochondrial membrane potential. This was accompanied by ROS production, elevation of intracellular Ca2+ levels and concomitant nuclear DNA fragmentation. We conclude that TFQ targets Leishmania mitochondria, leading to an apoptosis-like death process. PMID:20837758

Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis.

PubMed

Carvalho, Luis; Luque-Ortega, Juan Román; Manzano, José Ignacio; Castanys, Santiago; Rivas, Luis; Gamarro, Francisco

2010-12-01

Tafenoquine (TFQ), an 8-aminoquinoline analogue of primaquine, which is currently under clinical trial (phase IIb/III) for the treatment and prevention of malaria, may represent an alternative treatment for leishmaniasis. In this work, we have studied the mechanism of action of TFQ against Leishmania parasites. TFQ impaired the overall bioenergetic metabolism of Leishmania promastigotes, causing a rapid drop in intracellular ATP levels without affecting plasma membrane permeability. TFQ induced mitochondrial dysfunction through the inhibition of cytochrome c reductase (respiratory complex III) with a decrease in the oxygen consumption rate and depolarization of mitochondrial membrane potential. This was accompanied by ROS production, elevation of intracellular Ca(2+) levels and concomitant nuclear DNA fragmentation. We conclude that TFQ targets Leishmania mitochondria, leading to an apoptosis-like death process.

Investigation of mindin levels in hypertensive patients with left ventricular hypertrophy and QRS fragmentation on electrocardiography.

PubMed

Doğan, Tolga; Yetim, Mucahit; Çelik, Oğuzhan; Kalçık, Macit; Özcan, Oğuzhan; Doğan, İbrahim; Erenler, Ali Kemal; Bekar, Lütfü; Karavelioğlu, Yusuf

2017-12-21

Mindin was associated with diabetic nephropathy, podocyte injury, colitis, allergic asthma, liver ischaemia and reperpusion injury and ischaemic brain injury. On the other hand, it was reported as a protective factor against obesity, cardiac hypertrophy, fibrosis and remodelling. Fragmented QRS complexes (fQRS) are markers of altered ventricular depolarisation owing to a prior myocardial scar and fibrosis. In this study, we aimed to investigate mindin levels in hypertensive patients with left ventricular hypertrophy and fQRS on electrocardiography. This observational case-control study enrolled 70 (36 female) hypertensive patients with fQRS and 38 (23 female) hypertensive control patients. All patients were evaluated by transthoracic echocardiography. Mindin levels were measured by the enzyme-linked immunosorbent assay (ELISA). Clinical, echocardiographic and laboratory data were compared between patient and control groups. There was no significant difference between patient and control groups in terms of clinical, echocardiographic and routine laboratory parameters. The mindin levels were significantly higher in the patient group than controls (11.3 (7.21-19.31) vs 4.15 (2.86-6.34); p < .001). Multiple logistic regression analyses defined increased mindin levels as an independent predictor for the presence of fQRS (Odds ratio: 1.733; p = .034). Mindin levels >6.74 predicted the presence of fQRS with a sensitifity of 84.3% and specificity of 79.9% on receiver operating characteristic (ROC) curve analysis (The area under the curve:0.889; Confidence Interval: 0.827-0.951; p < .001). Mindin expressin is upregulated in hypertensive patients with fQRS complexes. In contrary to previous studies, increased mindin levels may be associated with myocardial fibrosis.

Feasibility of the music therapy assessment tool for awareness in disorders of consciousness (MATADOC) for use with pediatric populations.

PubMed

Magee, Wendy L; Ghetti, Claire M; Moyer, Alvin

2015-01-01

Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC) is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures' psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The music therapy assessment tool for awareness in disorders of consciousness (MATADOC) is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of pediatric DOC populations.

Feasibility of the music therapy assessment tool for awareness in disorders of consciousness (MATADOC) for use with pediatric populations

PubMed Central

Magee, Wendy L.; Ghetti, Claire M.; Moyer, Alvin

2015-01-01

Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC) is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures’ psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The music therapy assessment tool for awareness in disorders of consciousness (MATADOC) is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of pediatric DOC populations. PMID:26074850

[Therapeutic bacterial vaccine Immunovac in complex treatment of patients with chronic pyoderma].

PubMed

Sorokina, E V; Masiukova, S A; Kurbatova, E A; Egorova, N B

2010-01-01

Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma. Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma. Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment. Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

It's not that Difficult: An Interrater Reliability Study of the DSM–5 Section III Alternative Model for Personality Disorders

DOE PAGES

Garcia, Darren J.; Skadberg, Rebecca M.; Schmidt, Megan; ...

2018-03-05

The Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM–5]; American Psychiatric Association, 2013) Section III Alternative Model for Personality Disorders (AMPD) represents a novel approach to the diagnosis of personality disorder (PD). In this model, PD diagnosis requires evaluation of level of impairment in personality functioning (Criterion A) and characterization by pathological traits (Criterion B). Questions about clinical utility, complexity, and difficulty in learning and using the AMPD have been expressed in recent scholarly literature. We examined the learnability, interrater reliability, and clinical utility of the AMPD using a vignette methodology and graduate student raters. Results showed thatmore » student clinicians can learn Criterion A of the AMPD to a high level of interrater reliability and agreement with expert ratings. Interrater reliability of the 25 trait facets of the AMPD varied but showed overall acceptable levels of agreement. Examination of severity indexes of PD impairment showed the level of personality functioning (LPF) added information beyond that of global assessment of functioning (GAF). Clinical utility ratings were generally strong. Lastly, the satisfactory interrater reliability of components of the AMPD indicates the model, including the LPF, is very learnable.« less

It's not that Difficult: An Interrater Reliability Study of the DSM–5 Section III Alternative Model for Personality Disorders

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

Garcia, Darren J.; Skadberg, Rebecca M.; Schmidt, Megan

The Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM–5]; American Psychiatric Association, 2013) Section III Alternative Model for Personality Disorders (AMPD) represents a novel approach to the diagnosis of personality disorder (PD). In this model, PD diagnosis requires evaluation of level of impairment in personality functioning (Criterion A) and characterization by pathological traits (Criterion B). Questions about clinical utility, complexity, and difficulty in learning and using the AMPD have been expressed in recent scholarly literature. We examined the learnability, interrater reliability, and clinical utility of the AMPD using a vignette methodology and graduate student raters. Results showed thatmore » student clinicians can learn Criterion A of the AMPD to a high level of interrater reliability and agreement with expert ratings. Interrater reliability of the 25 trait facets of the AMPD varied but showed overall acceptable levels of agreement. Examination of severity indexes of PD impairment showed the level of personality functioning (LPF) added information beyond that of global assessment of functioning (GAF). Clinical utility ratings were generally strong. Lastly, the satisfactory interrater reliability of components of the AMPD indicates the model, including the LPF, is very learnable.« less

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of molds of the Fusarium genus.

PubMed

Triest, David; Stubbe, Dirk; De Cremer, Koen; Piérard, Denis; Normand, Anne-Cécile; Piarroux, Renaud; Detandt, Monique; Hendrickx, Marijke

2015-02-01

The rates of infection with Fusarium molds are increasing, and a diverse number of Fusarium spp. belonging to different species complexes can cause infection. Conventional species identification in the clinical laboratory is time-consuming and prone to errors. We therefore evaluated whether matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a useful alternative. The 289 Fusarium strains from the Belgian Coordinated Collections of Microorganisms (BCCM)/Institute of Hygiene and Epidemiology Mycology (IHEM) culture collection with validated sequence-based identities and comprising 40 species were used in this study. An identification strategy was developed, applying a standardized MALDI-TOF MS assay and an in-house reference spectrum database. In vitro antifungal testing was performed to assess important differences in susceptibility between clinically relevant species/species complexes. We observed that no incorrect species complex identifications were made by MALDI-TOF MS, and 82.8% of the identifications were correct to the species level. This success rate was increased to 91% by lowering the cutoff for identification. Although the identification of the correct species complex member was not always guaranteed, antifungal susceptibility testing showed that discriminating between Fusarium species complexes can be important for treatment but is not necessarily required between members of a species complex. With this perspective, some Fusarium species complexes with closely related members can be considered as a whole, increasing the success rate of correct identifications to 97%. The application of our user-friendly MALDI-TOF MS identification approach resulted in a dramatic improvement in both time and accuracy compared to identification with the conventional method. A proof of principle of our MALDI-TOF MS approach in the clinical setting using recently isolated Fusarium strains demonstrated its validity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies.

PubMed

Aleil, Boris; Meyer, Nicolas; Wolff, Valérie; Kientz, Daniel; Wiesel, Marie-Louise; Gachet, Christian; Cazenave, Jean-Pierre; Lanza, François

2006-10-01

Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.

Linguistic Feature Development Across Grades and Genre in Elementary Writing.

PubMed

Hall-Mills, Shannon; Apel, Kenn

2015-07-01

As children develop skills in writing across academic contexts, clinicians and educators need to have a fundamental understanding of typical writing development as well as valid and reliable assessment methods. The purpose of this study was to examine the progression of linguistic elements in school-age children's narrative and expository writing development. Narrative and expository writing samples produced by 89 children in Grades 2 through 4 were analyzed at the microstructure and macrostructure levels. Measures of receptive vocabulary, word-level reading, and reading comprehension were obtained. Exploratory factor analyses revealed 4 microstructure factors (e.g., productivity, grammatical complexity, grammatical accuracy, and lexical density) and 1 macrostructure factor (e.g., a combination of organization, text structure, and cohesion). Multivariate analyses of covariance with reading comprehension as a covariate showed that productivity and macrostructure were sensitive to grade-level and genre differences and that expository grammatical complexity was sensitive to grade-level differences. Findings are discussed in light of grade-level standards for narrative and expository writing and current practices in writing assessment. Multiple suggestions are offered for clinical and educational implications, and specific directions are provided for future research.

Anticoagulant treatment of medical patients with complex clinical conditions.

PubMed

Ruiz-Ruiz, F; Medrano, F J; Santos-Lozano, J M; Rodríguez-Torres, P; Navarro-Puerto, A; Calderón, E J

2018-06-12

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

The decisions regarding ADHD management (DRAMa) study: uncertainties and complexities in assessment, diagnosis and treatment, from the clinician's point of view.

PubMed

Kovshoff, Hanna; Williams, Sarah; Vrijens, May; Danckaerts, Marina; Thompson, Margaret; Yardley, Lucy; Hodgkins, Paul; Sonuga-Barke, Edmund J S

2012-02-01

Clinical decision making is influenced by a range of factors and constitutes an inherently complex task. Here we present results from the decisions regarding ADHD management (DRAMa) study in which we undertook a thematic analysis of clinicians' experiences and attitudes to assessment, diagnosis and treatment of ADHD. Fifty prescribing child psychiatrists and paediatricians from Belgium and the UK took part in semi-structured interviews about their decisions regarding the assessment, diagnosis and treatment of ADHD. Interviews were transcribed and processed using thematic analysis and the principles of grounded theory. Clinicians described the assessment and diagnostic process as inherently complicated and requiring time and experience to piece together the accounts of children made by multiple sources and through the use of varying information gathering techniques. Treatment decisions were viewed as a shared process between families, children, and the clinician. Published guidelines were viewed as vague, and few clinicians spoke about the use of symptom thresholds or specific impairment criteria. Furthermore, systematic or operationalised criteria to assess treatment outcomes were rarely used. Decision making in ADHD is regarded as a complicated, time consuming process which requires extensive use of clinical impression, and involves a partnership with parents. Clinicians want to separate biological from environmental causal factors to understand the level of impairment and the subsequent need for a diagnosis of ADHD. Clinical guidelines would benefit from revisions to take into account the real-world complexities of clinical decision making for ADHD.

"Real-life" treatment of chronic pain: Targets and goals.

PubMed

Ablin, Jacob N; Buskila, Dan

2015-02-01

Treating chronic pain is a complex challenge. While textbooks and medical education classically categorize pain as originating from peripheral (nociceptive), neuropathic, or centralized origins, in real life each and every patient may present a combination of various pain sources, types, and mechanisms. Moreover, individual patients may evolve and develop differing types of pain throughout their clinical follow-up, further emphasizing the necessity to maintain clinical diligence during the evaluation and follow-up of these patients. Rational treatment of patients suffering from chronic pain must attempt at deconstructing complex pain cases, identifying variegate pain generators, and targeting them with appropriate interventions, while incorporating both pharmacological and non-pharmacological strategies, rather than focusing on the total pain level, which represents an integral of all pain types. Failing to recognize the coexistence of different types of pain in an individual patient and escalating medications only on the basis of total pain intensity are liable to lead to both ineffective control of pain and increased untoward effects. In the current review, we outline strategies for deconstructing complex pain and therapeutic suggestions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Current status of the use of modalities in wound care: electrical stimulation and ultrasound therapy.

PubMed

Ennis, William J; Lee, Claudia; Plummer, Malgorzata; Meneses, Patricio

2011-01-01

Wound healing is a complex pathway that requires cells, an appropriate biochemical environment (i.e., cytokines, chemokines), an extracellular matrix, perfusion, and the application of both macrostrain and microstrain. The process is both biochemically complex and energy dependent. Healing can be assisted in difficult cases through the use of physical modalities. In the current literature, there is much debate over which treatment modality, dosage level, and timing is optimal. The mechanism of action for both electrical stimulation and ultrasound are reviewed along with possible clinical applications for the plastic surgeon.

Direct spectrophotometric measurement of supra-physiological levels of ascorbate in plasma.

PubMed

Witmer, Jordan R; Wetherell, Bailey J; Wagner, Brett A; Du, Juan; Cullen, Joseph J; Buettner, Garry R

2016-08-01

Supra-physiological concentrations of ascorbate, vitamin C, in blood, greater than 1mM, achieved through intravenous administration (IV), are being tested in clinical trials to treat human disease, e.g. cancer. These trials need information on the high levels of ascorbate achieved in blood upon IV administration of pharmacological ascorbate so appropriate clinical decisions can be made. Here we demonstrate that in the complex matrix of human blood plasma supra-physiological levels of ascorbate can be quantified by direct UV spectroscopy with use of a microvolume UV-vis spectrophotometer. Direct quantitation of ascorbate in plasma in the range of 2.9mM, lower limit of detection, up to at least 35mM can be achieved without any sample processing, other than centrifugation. This approach is rapid, economical, and can be used to quantify supraphysiological blood levels of ascorbate associated with the use of IV administration of pharmacological ascorbate to treat disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

What does it mean to be youth-friendly? Results from qualitative interviews with health care providers and clinic staff serving youth and young adults living with HIV.

PubMed

Saberi, Parya; Ming, Kristin; Dawson-Rose, Carol

2018-01-01

Given the consistent associations between younger age and numerous suboptimal clinical outcomes, there is a critical need for more research in youth living with human immunodeficiency virus (YLWH) and tailoring of health care delivery to the unique and complex needs of this population. The objective of this study was to examine the facilitators of and barriers to engagement in care among YLHW at the system and provider/staff level, as well as the barriers to using technology-based forms of communication with YLWH to improve retention and engagement in care. We conducted in-depth qualitative interviews with health care providers and staff members at the clinics and organizations serving YLWH in the San Francisco Bay Area. We interviewed 17 health care providers and staff members with a mean of 8 years of experience in providing clinical care to YLWH. Interviewees noted various facilitators of and barriers to engagement in care among YLWH, including the environment of the clinic (e.g., clinic location and service setting), provision of youth-friendly services (e.g., flexible hours and use of technology), and youth-friendly providers/staff (e.g., nonjudgmental approach). With regard to barriers to using technology in organizations and clinics, interviewees discussed the challenges at the system level (e.g., availability of technology, clinic capacity, and Health Insurance Portability and Accountability Act compliance), provider/staff level (e.g., time constraints and familiarity with technology), and youth level (e.g., changing of cellular telephones and relationship with provider/staff). Given the need for improved clinical outcomes among YLWH, our results can provide guidance for clinics and institutions providing care for this population to enhance the youth-friendliness of their services and examine their guidelines around the use of technology.

Managing clinical failure: a complex adaptive system perspective.

PubMed

Matthews, Jean I; Thomas, Paul T

2007-01-01

The purpose of this article is to explore the knowledge capture process at the clinical level. It aims to identify factors that enable or constrain learning. The study applies complex adaptive system thinking principles to reconcile learning within the NHS. The paper uses a qualitative exploratory study with an interpretative methodological stance set in a secondary care NHS Trust. Semi-structured interviews were conducted with healthcare practitioners and managers involved at both strategic and operational risk management processes. A network structure is revealed that exhibits the communication and interdependent working practices to support knowledge capture and adaptive learning. Collaborative multidisciplinary communities, whose values reflect local priorities and promote open dialogue and reflection, are featured. The main concern is that the characteristics of bureaucracy; rational-legal authority, a rule-based culture, hierarchical lines of communication and a centralised governance focus, are hindering clinical learning by generating barriers. Locally emergent collaborative processes are a key strategic resource to capture knowledge, potentially fostering an environment that could learn from failure and translate lessons between contexts. What must be addressed is that reporting mechanisms serve not only the governance objectives, but also supplement learning by highlighting the potential lessons in context. Managers must nurture a collaborative infrastructure using networks in a co-evolutionary manner. Their role is not to direct and design processes but to influence, support and create effective knowledge capture. Although the study only investigated one site the findings and conclusions may well translate to other trusts--such as the risk of not enabling a learning environment at clinical levels.

Assessment of pathology instruction in U.S. Dental hygiene educational programs.

PubMed

Jacobs, Barbara B; Lazar, Ann A; Rowe, Dorothy J

2015-04-01

To assess the instruction of pathology content in entry-level and advanced practitioner dental hygiene educational programs and the program directors' perceptions whether their graduates are adequately prepared to meet the increasingly complex medical and oral health needs of the public. A 28-question survey of instructional content and perceptions was developed and distributed using Qualtrics® software to the 340 directors of entry-level and advanced practitioner dental hygiene programs in the US. Respondents rated their level of agreement to a series of statements regarding their perceptions of graduates' preparation to perform particular dental hygiene services associated with pathology. Descriptive statistics for all 28 categorical survey questions were calculated and presented as the frequency (percentage). Of the 340 directors surveyed, 130 (38%) responded. Most entry-level respondents (53%) agreed or strongly agreed (29%) that their graduates were adequately prepared to meet the complex medical and oral health needs of the public, while all respondents of advanced practitioner programs strongly agreed. More respondents strongly agreed to statements related to clinical instruction than to didactic courses. While 64% of respondents agreed that their graduates were prepared to practice unsupervised, if it were legally allowed, 21% were ambivalent. The extent of pathology instruction in entry-level programs varied, but most used traditional formats of instruction, educational resources and assessments of educational outcomes. Advanced practitioner programs emphasized histological and clinical examination of oral lesions and patient case studies. Strengthening pathology instruction would ensure that future generations of dental hygienists would be adequately prepared to treat medically compromised patients. Copyright © 2015 The American Dental Hygienists’ Association.

Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

PubMed Central

Gao, Jianjiong; Aksoy, Bülent Arman; Dogrusoz, Ugur; Dresdner, Gideon; Gross, Benjamin; Sumer, S. Onur; Sun, Yichao; Jacobsen, Anders; Sinha, Rileen; Larsson, Erik; Cerami, Ethan; Sander, Chris; Schultz, Nikolaus

2014-01-01

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. PMID:23550210

Primary complex motor stereotypies in older children and adolescents: clinical features and longitudinal follow-up.

PubMed

Oakley, Christopher; Mahone, E Mark; Morris-Berry, Christina; Kline, Tina; Singer, Harvey S

2015-04-01

Complex motor stereotypies are rhythmic, repetitive, fixed, and purposeless movements that stop with distraction. Once believed to occur only in children with autism spectrum or other developmental disorders, their presence in otherwise typically developing children (primary) has been well-established. In primary complex motor stereotypies, little information is available about the long-term outcome of these movements or existing comorbidities. Forty-nine healthy participants (31 boys), ages 9 to 20 years with primary complex motor stereotypies who were previously diagnosed at a pediatric movements disorder clinic, were identified from medical records. Parents or the young adult (if older than age 18), completed a telephone interview evaluating family history, outcome, and comorbidities including attention-deficit hyperactivity disorder, obsessive compulsive disorder, anxiety, and tics/Tourette syndrome. Standardized questionnaires assessing attention-deficit hyperactivity, obsessive compulsive disorder, and anxiety were used to validate parent report of comorbidities. Stereotypy onset occurred before age 3 years in 98%. In all but one individual, stereotypies persisted at the time of phone follow-up (follow-up range: 6.8-20.3 years). Positive family history of complex motor stereotypies was identified in 39%. Most participants (92%) had concern for at least one comorbid disorder, including parent-/patient-reported clinically elevated levels of anxiety (73%), attention-deficit hyperactivity (63%), obsessive compulsive disorder (35%), and tics/Tourette syndrome (22%). Primary motor stereotypies typically begin in early childhood and, although reduced in frequency and duration, persist at least through the teenage years. Repetitive movements are associated with a variety of comorbidities that often have a greater functional impact than the stereotypic behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Application of gray level mapping in computed tomographic colonography: a pilot study to compare with traditional surface rendering method for identification and differentiation of endoluminal lesions

PubMed Central

Chen, Lih-Shyang; Hsu, Ta-Wen; Chang, Shu-Han; Lin, Chih-Wen; Chen, Yu-Ruei; Hsieh, Chin-Chiang; Han, Shu-Chen; Chang, Ku-Yaw; Hou, Chun-Ju

2017-01-01

Objective: In traditional surface rendering (SR) computed tomographic endoscopy, only the shape of endoluminal lesion is depicted without gray-level information unless the volume rendering technique is used. However, volume rendering technique is relatively slow and complex in terms of computation time and parameter setting. We use computed tomographic colonography (CTC) images as examples and report a new visualization technique by three-dimensional gray level mapping (GM) to better identify and differentiate endoluminal lesions. Methods: There are 33 various endoluminal cases from 30 patients evaluated in this clinical study. These cases were segmented using gray-level threshold. The marching cube algorithm was used to detect isosurfaces in volumetric data sets. GM is applied using the surface gray level of CTC. Radiologists conducted the clinical evaluation of the SR and GM images. The Wilcoxon signed-rank test was used for data analysis. Results: Clinical evaluation confirms GM is significantly superior to SR in terms of gray-level pattern and spatial shape presentation of endoluminal cases (p < 0.01) and improves the confidence of identification and clinical classification of endoluminal lesions significantly (p < 0.01). The specificity and diagnostic accuracy of GM is significantly better than those of SR in diagnostic performance evaluation (p < 0.01). Conclusion: GM can reduce confusion in three-dimensional CTC and well correlate CTC with sectional images by the location as well as gray-level value. Hence, GM increases identification and differentiation of endoluminal lesions, and facilitates diagnostic process. Advances in knowledge: GM significantly improves the traditional SR method by providing reliable gray-level information for the surface points and is helpful in identification and differentiation of endoluminal lesions according to their shape and density. PMID:27925483

Nursing Practice Should Be Informed by the Best Available Evidence, but Should All First-Level Nurses Be Competent at Research Appraisal and Utilization?

ERIC Educational Resources Information Center

White, Robert; Taylor, Shirley

2002-01-01

The British model of nurses as finders, appraisers, and users of research in practice is unattainable, given the technical complexity of research and the skills and time required. Clinical governance mechanisms and accountability demands further undermine the approach. An alternative is development of nursing research specialists and…

Graduate Student WAIS-III Scoring Accuracy Is a Function of Full Scale IQ and Complexity of Examiner Tasks

ERIC Educational Resources Information Center

Hopwood, Christopher J.; Richard, David C. S.

2005-01-01

Research on the Wechsler Adult Intelligence Scale-Revised and Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) suggests that practicing clinical psychologists and graduate students make item-level scoring errors that affect IQ, index, and subtest scores. Studies have been limited in that Full-Scale IQ (FSIQ) and examiner administration,…

The NSL chromatin-modifying complex subunit KANSL2 regulates cancer stem-like properties in glioblastoma that contribute to tumorigenesis

PubMed Central

Ferreyra-Solari, Nazarena; Belforte, Fiorella S.; Canedo, Lucía; Videla-Richardson, Guillermo A.; Espinosa, Joaquín M.; Rossi, Mario; Serna, Eva; Riudavets, Miguel A.; Martinetto, Horacio; Sevlever, Gustavo; Perez-Castro, Carolina

2016-01-01

KANSL2 is an integral subunit of the Non-Specific Lethal (NSL) chromatin-modifying complex which contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. PMID:27406830

Capacity of clinical pathways--a strategic multi-level evaluation tool.

PubMed

Cardoen, Brecht; Demeulemeester, Erik

2008-12-01

In this paper we strategically evaluate the efficiency of clinical pathways and their complex interdependencies with respect to joint resource usage and patient throughput. We propose a discrete-event simulation approach that allows for the simultaneous evaluation of multiple clinical pathways and the inherent uncertainty (resource, duration and arrival) that accompanies medical processes. Both the consultation suite and the surgery suite may be modeled and examined in detail by means of sensitivity or scenario analyses. Since each medical facility can somehow be represented as a combination of clinical pathways, i.e. they are conceptually similar, the simulation model is generic in nature. Next to the formulation of the model, we illustrate its applicability by means of a case study that was conducted in a Belgian hospital.

Peer assisted learning in the clinical setting: an activity systems analysis.

PubMed

Bennett, Deirdre; O'Flynn, Siun; Kelly, Martina

2015-08-01

Peer assisted learning (PAL) is a common feature of medical education. Understanding of PAL has been based on processes and outcomes in controlled settings, such as clinical skills labs. PAL in the clinical setting, a complex learning environment, requires fresh evaluation. Socio-cultural theory is proposed as a means to understand educational interventions in ways that are practical and meaningful. We describe the evaluation of a PAL intervention, introduced to support students' transition into full time clinical attachments, using activity theory and activity systems analysis (ASA). Our research question was How does PAL transfer to the clinical environment? Junior students on their first clinical attachments undertook a weekly same-level, reciprocal PAL activity. Qualitative data was collected after each session, and focus groups (n = 3) were held on completion. Data was analysed using ASA. ASA revealed two competing activity systems on clinical attachment; Learning from Experts, which students saw as the primary function of the attachment and Learning with Peers, the PAL intervention. The latter took time from the first and was in tension with it. Tensions arose from student beliefs about how learning takes place in clinical settings, and the importance of social relationships, leading to variable engagement with PAL. Differing perspectives within the group were opportunities for expansive learning. PAL in the clinical environment presents challenges specific to that context. Using ASA helped to describe student activity on clinical attachment and to highlight tensions and contradictions relating PAL in that setting. Planning learning opportunities on clinical placements, must take account of how students learn in workplaces, and the complexity of the multiple competing activity systems related to learning and social activities.

Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies

PubMed Central

Lang, Bethan; Makuch, Mateusz; Moloney, Teresa; Dettmann, Inga; Mindorf, Swantje; Probst, Christian; Stoecker, Winfried; Buckley, Camilla; Newton, Charles R; Leite, M Isabel; Maddison, Paul; Komorowski, Lars; Adcock, Jane; Vincent, Angela; Waters, Patrick; Irani, Sarosh R

2017-01-01

Objectives Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. Methods Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125I-αDTX and 125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. Results VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical–serological correlations and a limited immunotherapy response. Conclusions Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies. PMID:28115470

Expression of Truncated Neurokinin-1 Receptor in Childhood Neuroblastoma is Independent of Tumor Biology and Stage.

PubMed

Pohl, Alexandra; Kappler, Roland; Mühling, Jakob; VON Schweinitz, Dietrich; Berger, Michael

2017-11-01

Neuroblastoma is an embryonal malignancy arising from the aberrant growth of neural crest progenitor cells of the sympathetic nervous system. The tachykinin receptor 1 (TACR1) - substance P complex is associated with tumoral angiogenesis and cell proliferation in a variety of cancer types. Inhibition of TACR1 was recently described to impede growth of NB cell lines. However, the relevance of TACR1 in clinical settings is unknown. We investigated gene expression levels of full-length and truncated TACR1 in 59 neuroblastomas and correlated these data with the patients' clinical parameters such as outcome, metastasis, International Neuroblastoma Staging System (INSS) status, MYCN proto-oncogene, bHLH transcription factor (MYCN) status, gender and age. Our results indicated that TACR1 is ubiquitously expressed in neuroblastoma but expression levels are independent of clinical parameters. Our data suggest that TACR1 might serve as a potent anticancer target in a large variety of patients with neuroblastoma, independent of tumor biology and clinical stage. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease.

PubMed

Freund, Brin; Probasco, John C; Cervenka, Mackenzie C; Sutter, Raoul; Kaplan, Peter W

2018-05-01

Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P < .006). On neuroimaging, diffusion restriction in the cortex ( P = .001), caudate ( P < .001), and putamen ( P = .001) was more frequent in CJD. Periodic sharp wave complexes ( P = .001) and generalized suppressed activity ( P = .008) were more common on initial EEG in CJD. On serial EEGs, generalized periodic discharges ( P = .004), generalized suppressed activity (P=0.008), and periodic sharp wave complexes ( P < .001) were detected more in CJD. This study shows that there are a number of differentiating features between CJD and VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions.

Real-time monitoring of clinical processes using complex event processing and transition systems.

PubMed

Meinecke, Sebastian

2014-01-01

Dependencies between tasks in clinical processes are often complex and error-prone. Our aim is to describe a new approach for the automatic derivation of clinical events identified via the behaviour of IT systems using Complex Event Processing. Furthermore we map these events on transition systems to monitor crucial clinical processes in real-time for preventing and detecting erroneous situations.

A grid to facilitate physics staffing justification.

PubMed

Klein, Eric E

2009-12-03

Justification of clinical physics staffing levels is difficult due to the lack of direction as how to equate clinical needs with the staffing levels and competency required. When a physicist negotiates staffing requests to administration, she/he often refers to American College of Radiology staffing level suggestions, and resources such as the Abt studies. This approach is often met with questions as to how to fairly derive the time it takes to perform tasks. The result is often insufficient and/or inexperienced staff handling complex and cumbersome tasks. We undertook development of a staffing justification grid to equate the clinical needs to the quantity and quality of staffing required. The first step is using the Abt study, customized to the clinical setting, to derive time per task multiplied by the anticipated number of such tasks. Inclusion of vacation, meeting, and developmental time may be incorporated along with allocated time for education and administration. This is followed by mapping the tasks to the level of competency/experience needed. For example, in an academic setting the faculty appointment levels correlate with experience. Non-staff personnel, such as IMRT QA technicians or clerical staff, should also be part of the equation. By using the staffing justification grid, we derived strong documentation to justify a substantial budget increase. The grid also proved useful when our clinical demands changed. Justification for physics staffing can be significantly strengthened with a properly developed data-based time and work analysis. A staffing grid is presented, along with a development methodology that facilitated our justification. Though our grid is for a large academic facility, the methodology can be extended to a non-academic setting, and to a smaller scale. This grid method not only equates the clinical needs with the quantity of staffing, but can also help generate the personnel budget, based on the type of staff and personnel required. The grid is easily adaptable when changes to the clinical environment change, such as an increase in IMRT or IGRT applications.

Correlations between Clinical Judgement and Learning Style Preferences of Nursing Students in the Simulation Room

PubMed Central

Hallin, Karin; Häggström, Marie; Bäckström, Britt; Kristiansen, Lisbeth Porskrog

2016-01-01

Background: Health care educators account for variables affecting patient safety and are responsible for developing the highly complex process of education planning. Clinical judgement is a multidimensional process, which may be affected by learning styles. The aim was to explore three specific hypotheses to test correlations between nursing students’ team achievements in clinical judgement and emotional, sociological and physiological learning style preferences. Methods: A descriptive cross-sectional study was conducted with Swedish university nursing students in 2012-2013. Convenience sampling was used with 60 teams with 173 nursing students in the final semester of a three-year Bachelor of Science in nursing programme. Data collection included questionnaires of personal characteristics, learning style preferences, determined by the Dunn and Dunn Productivity Environmental Preference Survey, and videotaped complex nursing simulation scenarios. Comparison with Lasater Clinical Judgement Rubric and Non-parametric analyses were performed. Results: Three significant correlations were found between the team achievements and the students’ learning style preferences: significant negative correlation with ‘Structure’ and ‘Kinesthetic’ at the individual level, and positive correlation with the ‘Tactile’ variable. No significant correlations with students’ ‘Motivation’, ‘Persistence’, ‘Wish to learn alone’ and ‘Wish for an authoritative person present’ were seen. Discussion and Conclusion: There were multiple complex interactions between the tested learning style preferences and the team achievements of clinical judgement in the simulation room, which provides important information for the becoming nurses. Several factors may have influenced the results that should be acknowledged when designing further research. We suggest conducting mixed methods to determine further relationships between team achievements, learning style preferences, cognitive learning outcomes and group processes. PMID:26755461

Arthroscopic repair of lateral ankle ligament complex by suture anchor.

PubMed

Wang, Jingwei; Hua, Yinghui; Chen, Shiyi; Li, Hongyun; Zhang, Jian; Li, Yunxia

2014-06-01

Arthroscopic repair of the lateral ligament complex with suture anchors is increasingly used to treat chronic ankle instability (CAI). Our aims are (1) to analyze and evaluate the literature on arthroscopic suture anchor repair of the anterior talofibular ligament and (2) to conduct a systematic review of the clinical evidence on the reported outcomes and complications of treating CAI with this technique. We performed a systematic review of the literature using PubMed, Ovid, Elsevier ScienceDirect, Web of Science-Conference Proceedings Citation Index, and the Cochrane Database of Systematic Reviews from 1987 to September 2013. Clinical studies using the arthroscopic suture anchor technique to treat CAI were included. Outcome measures consisted of clinical assessment of postoperative ligament stability and complications. In addition, the methodologic quality of the included studies was assessed by use of the modified Coleman Methodology Score. After reviewing 371 studies, we identified 6 studies (5 retrospective case series and 1 prospective case series, all Level IV) that met the inclusion criteria, with a mean Coleman Methodology Score of 71.8 ± 7.52 (range, 63 to 82). In these studies 178 patients (179 ankles) underwent arthroscopic suture anchor repair of the anterior talofibular ligament with a mean follow-up period of 38.9 months (range, 6 to 117.6 months). All patients were reported to have subjective improvement of their ankle instability, with complications in 31 cases. Studies of arthroscopic suture anchor technique to treat CAI are sparse, with moderate mean methodologic quality. The included studies suggest that the arthroscopic technique is a feasible procedure to restore ankle stability; however, on the basis of our review, this technique seems to be associated with a relatively high complication rate. Extensive cadaveric studies, clinical trials, and comparative studies comparing arthroscopic and open repair should be performed in the future. Level IV, systematic review of Level IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Results from the cognitive changes and retirement among senior surgeons self-report survey.

PubMed

Lee, H Jin; Drag, Lauren L; Bieliauskas, Linas A; Langenecker, Scott A; Graver, Christopher; O'Neill, Jillian; Greenfield, Lazar

2009-11-01

The Cognitive Changes and Retirement among Senior Surgeons (CCRASS) study suggested that although subjective cognitive awareness may play a role in surgeons' retirement decisions, self-perceived cognitive decline did not predict objective cognitive performance. This article summarizes results from all participants who completed the survey portion of the CCRASS study. A survey examining subjective cognitive changes, changes in caseload, involvement in new technology, and retirement decisions, was administered to 995 surgeons at annual meetings of the Clinical Congress of the American College of Surgeons between 2001 and 2006. Forty-five percent reported increased caseload volume and 48% reported increased caseload complexity during the previous 5 years. In addition, 75% and 73% denied any recent changes in memory recall or name recognition, respectively. Increasing age was associated with decreases in clinical caseload and complexity. The majority of respondents across all age groups reported active participation in either learning (64%) or contributing (13%) to new technology in the field. Among surgeons with no imminent plans for retirement, 58% reported that a retirement decision will be based on skill level. Increasing age was associated with decreases in caseload and case complexity. But a steady proportion of surgeons, even in the oldest age group, are active in new surgical innovations and challenging cases. Most reported no changes in perceived cognitive abilities. The majority of surgeons who had made no decision to retire reported that their decision will be based on skill level rather than age.

Genetic tests in major psychiatric disorders-integrating molecular medicine with clinical psychiatry-why is it so difficult?

PubMed

Demkow, U; Wolańczyk, T

2017-06-13

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays' medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease.

Genetic tests in major psychiatric disorders—integrating molecular medicine with clinical psychiatry—why is it so difficult?

PubMed Central

Demkow, U; Wolańczyk, T

2017-01-01

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays’ medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease. PMID:28608853

Challenges in recruitment and retention of clinical trial subjects.

PubMed

Kadam, Rashmi Ashish; Borde, Sanghratna Umakant; Madas, Sapna Amol; Salvi, Sundeep Santosh; Limaye, Sneha Saurabh

2016-01-01

Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.

Periodontal status of patients with dentin dysplasia type I: report of three cases within a family.

PubMed

Da Rós Gonçalves, Lorena; Oliveira, Cristiana Aroeira G R; Holanda, Rose; Silva-Boghossian, Carina M; Colombo, Ana Paula Vieira; Maia, Lucianne Cople; Feres-Filho, Eduardo Jorge

2008-07-01

Dentin dysplasia type I (DDI) is a rare hereditary disturbance of dentin formation. It is characterized by clinically normal-appearing crowns; obliteration of pulp chambers; and short, blunted and malformed roots that are commonly associated with periodontal attachment loss (PAL). In this context, we report three cases within a family with similar clinical and radiographic features of DDI but with differing microbiologic and periodontal conditions. A 42-year-old white female and her two daughters (25 and 10 years of age) presented with a diagnosis of DDI. Probing depth (PD), clinical attachment level (CAL), visible plaque, and bleeding on probing (BOP) were recorded. Subgingival biofilm samples were randomly collected and analyzed by checkerboard DNA-DNA hybridization. The mother presented 34.9% of sites with PD > or =4 mm, 41.3% of sites with CAL > or =4 mm, and 57% of sites with BOP; both daughters presented no sites with PD or CAL >3 mm and <10% of sites with BOP. Microbiologic analysis detected Gemella morbillorum, Neisseria mucosa, and Staphylococcus aureus in > or =50% of the mother's samples. The daughters showed high levels (>10(4) bacterial cells) of some periodontopathic bacteria, including members of the red (Porphyromonas gingivalis) and orange (Fusobacterium periodonticum and F. nucleatum polymorphum) complexes and beneficial species of the yellow (Streptococcus gordonii) and purple (Veillonella parvula) complexes. The mother presented high mean levels only for four tested species (N. mucosa, Prevotella melaninogenica, Treponema denticola, and V. parvula). A combination of radiographs, microbiologic analysis, and preventive professional monitoring care is important to avoid PAL and to provide oral health in patients with DDI.

Evaluating the effects of cognitive support on psychiatric clinical comprehension.

PubMed

Dalai, Venkata V; Khalid, Sana; Gottipati, Dinesh; Kannampallil, Thomas; John, Vineeth; Blatter, Brett; Patel, Vimla L; Cohen, Trevor

2014-10-01

Clinicians' attention is a precious resource, which in the current healthcare practice is consumed by the cognitive demands arising from complex patient conditions, information overload, time pressure, and the need to aggregate and synthesize information from disparate sources. The ability to organize information in ways that facilitate the generation of effective diagnostic solutions is a distinguishing characteristic of expert physicians, suggesting that automated systems that organize clinical information in a similar manner may augment physicians' decision-making capabilities. In this paper, we describe the design and evaluation of a theoretically driven cognitive support system (CSS) that assists psychiatrists in their interpretation of clinical cases. The system highlights, and provides the means to navigate to, text that is organized in accordance with a set of diagnostically and therapeutically meaningful higher-level concepts. To evaluate the interface, 16 psychiatry residents interpreted two clinical case scenarios, with and without the CSS. Think-aloud protocols captured during their interpretation of the cases were transcribed and analyzed qualitatively. In addition, the frequency and relative position of content related to key higher-level concepts in a verbal summary of the case were evaluated. In addition the transcripts from both groups were compared to an expert derived reference standard using latent semantic analysis (LSA). Qualitative analysis showed that users of the system better attended to specific clinically important aspects of both cases when these were highlighted by the system, and revealed ways in which the system mediates hypotheses generation and evaluation. Analysis of the summary data showed differences in emphasis with and without the system. The LSA analysis suggested users of the system were more "expert-like" in their emphasis, and that cognitive support was more effective in the more complex case. Cognitive support impacts upon clinical comprehension. This appears to be largely helpful, but may also lead to neglect of information (such as the psychosocial history) that the system does not highlight. The results have implications for the design of CSSs for clinical narratives including the role of information organization and textual embellishments for more efficient clinical case presentation and comprehension. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluating the effects of cognitive support on psychiatric clinical comprehension

PubMed Central

Dalai, Venkata V.; Khalid, Sana; Gottipati, Dinesh; Kannampallil, Thomas; John, Vineeth; Blatter, Brett; Patel, Vimla L.; Cohen, Trevor

2014-01-01

Objective Clinicians’ attention is a precious resource, which in the current healthcare practice is consumed by the cognitive demands arising from complex patient conditions, information overload, time pressure, and the need to aggregate and synthesize information from disparate sources. The ability to organize information in ways that facilitate the generation of effective diagnostic solutions is a distinguishing characteristic of expert physicians, suggesting that automated systems that organize clinical information in a similar manner may augment physicians’ decision-making capabilities. In this paper, we describe the design and evaluation of a theoretically driven cognitive support system (CSS) that assists psychiatrists in their interpretation of clinical cases. The system highlights, and provides the means to navigate to, text that is organized in accordance with a set of diagnostically and therapeutically meaningful higher-level concepts. Methods and Materials To evaluate the interface, 16 psychiatry residents interpreted two clinical case scenarios, with and without the CSS. Think-aloud protocols captured during their interpretation of the cases were transcribed and analyzed qualitatively. In addition, the frequency and relative position of content related to key higher-level concepts in a verbal summary of the case were evaluated. In addition the transcripts from both groups were compared to an expert derived reference standard using latent semantic analysis (LSA). Results Qualitative analysis showed that users of the system better attended to specific clinically important aspects of both cases when these were highlighted by the system, and revealed ways in which the system mediates hypotheses generation and evaluation. Analysis of the summary data showed differences in emphasis with and without the system. The LSA analysis suggested users of the system were more “expert-like” in their emphasis, and that cognitive support was more effective in the more complex case. Conclusions Cognitive support impacts upon clinical comprehension. This appears to be largely helpful, but may also lead to neglect of information (such as the psychosocial history) that the system does not highlight. The results have implications for the design of CSSs for clinical narratives including the role of information organization and textual embellishments for more efficient clinical case presentation and comprehension. PMID:25179216

Parental Understanding of Tuberous Sclerosis Complex.

PubMed

Samia, Pauline; Donald, Kirsten A; Schlegel, Birgit; Wilmshurst, Jo M

2015-09-01

Tuberous sclerosis complex is a genetic disorder with multisystem involvement that poses significant challenges to the affected child and family. Caregiver knowledge in the South African population has not previously been reported. A prospective study of the parents of 21 children with tuberous sclerosis complex was undertaken. Median parental age was 38 (interquartile range 34.5-45) years. Parents were randomly allocated to receive written information about the condition, or to receive verbal counseling already established in clinic. A significant difference (P = .001) was observed in the change in the mean knowledge scores for the parent group that received written information (34.2 at baseline, 51.7 at the second visit. This impact was higher in parents with an education level of at least grade 8 (P = .003). Parental understanding of tuberous sclerosis complex can be improved by provision of written information and should be routinely available in a readily understandable format. © The Author(s) 2014.

A case for the sentence in reading comprehension.

PubMed

Scott, Cheryl M

2009-04-01

This article addresses sentence comprehension as a requirement of reading comprehension within the framework of the narrow view of reading that was advocated in the prologue to this forum. The focus is on the comprehension requirements of complex sentences, which are characteristic of school texts. Topics included in this discussion are (a) evidence linking sentence comprehension and syntax with reading, (b) syntactic properties of sentences that make them difficult to understand, (c) clinical applications for the assessment of sentence comprehension as it relates to reading, and (d) evidence and methods for addressing sentence complexity in treatment. Sentence complexity can create comprehension problems for struggling readers. The contribution of sentence comprehension to successful reading has been overlooked in models that emphasize domain-general comprehension strategies at the text level. The author calls for the evaluation of sentence comprehension within the context of content domains where complex sentences are found.

Aerobic metabolism underlies complexity and capacity

PubMed Central

Koch, Lauren G; Britton, Steven L

2008-01-01

The evolution of biological complexity beyond single-celled organisms was linked temporally with the development of an oxygen atmosphere. Functionally, this linkage can be attributed to oxygen ranking high in both abundance and electronegativity amongst the stable elements of the universe. That is, reduction of oxygen provides for close to the largest possible transfer of energy for each electron transfer reaction. This suggests the general hypothesis that the steep thermodynamic gradient of an oxygen environment was permissive for the development of multicellular complexity. A corollary of this hypothesis is that aerobic metabolism underwrites complex biological function mechanistically at all levels of organization. The strong contemporary functional association of aerobic metabolism with both physical capacity and health is presumably a product of the integral role of oxygen in our evolutionary history. Here we provide arguments from thermodynamics, evolution, metabolic network analysis, clinical observations and animal models that are in accord with the centrality of oxygen in biology. PMID:17947307

The complexity of nurses' attitudes toward euthanasia: a review of the literature.

PubMed

Berghs, M; Dierckx de Casterlé, B; Gastmans, C

2005-08-01

In this literature review, a picture is given of the complexity of nursing attitudes toward euthanasia. The myriad of data found in empirical literature is mostly framed within a polarised debate and inconclusive about the complex reality behind attitudes toward euthanasia. Yet, a further examination of the content as well as the context of attitudes is more revealing. The arguments for euthanasia have to do with quality of life and respect for autonomy. Arguments against euthanasia have to do with non-maleficence, sanctity of life, and the notion of the slippery slope. When the context of attitudes is examined a number of positive correlates for euthanasia such as age, nursing specialty, and religion appear. In a further analysis of nurses' comments on euthanasia, it is revealed that part of the complexity of nursing attitudes toward euthanasia arises because of the needs of nurses at the levels of clinical practice, communication, emotions, decision making, and ethics.

Sentence comprehension in agrammatic aphasia: history and variability to clinical implications.

PubMed

Johnson, Danielle; Cannizzaro, Michael S

2009-01-01

Individuals with Broca's aphasia often present with deficits in their ability to comprehend non-canonical sentences. This has been contrastingly characterized as a systematic loss of specific grammatical abilities or as individual variability in the dynamics between processing load and resource availability. The present study investigated sentence level comprehension in participants with Broca's aphasia in an attempt to integrate these contrasting views into a clinically useful process. Two participants diagnosed with Broca's aphasia were assessed using a sentence-to-picture matching paradigm and a truth-value judgement task, across sentence constructions thought to be problematic for this population. The data demonstrate markedly different patterns of performance between participants, as well as variability within participants (e.g. by sentence type). These findings support the notion of individual performance variability in persons with aphasia. Syntactic theory was instructive for assessing sentence level comprehension, leading to a clinically relevant process of identifying treatment targets considering both performance variability and syntactic complexity for this population.

Fluorimetric quantitation of citalopram and escitalopram in plasma: developing an express method to monitor compliance in clinical trials.

PubMed

Serebruany, Victor; Malinin, Alex; Dragan, Vadim; Atar, Dan; van Zyl, Louis; Dragan, Anatoly

2007-01-01

Selective serotonin reuptake inhibitors (SSRIs) in general, and citalopram/escitalopram in particular, are widely used to treat clinical depression. However, SSRI bioavailability and non-compliance represent major issues, especially in the clinical trials setting. In this context, frequent drug-level measurements for compliance monitoring would be a desirable tool to improve clinical outcomes with SSRIs. However, the liquid chromatography techniques available are expensive, requiring excessive sample preparation, and suffer from high complexity. We sought to develop a rapid method for the measurement of citalopram/escitalopram levels in human plasma by fluorimetry. A total of 34 frozen human plasma samples were thawed at room temperature and repeatedly centrifuged in cellulose to remove aggregates, proteins and solids. Fluorescence spectra were measured in the range 270-450 nm with excitation at 240 nm on a FluoroMax 3 spectrofluorimeter. Control samples contained known concentrations of SSRIs. SSRI absorbance spectra were recorded in the range 230-320 nm. The shape of the spectra and the absorbance of citalopram and escitalopram were very similar, with UV maximum absorbance at 239 nm. The maximum extinction coefficient was epsilon239=15,930 M-1 cm-1 for citalopram and epsilon239=13,630 M-1 cm-1 for escitalopram. The fluorescence spectra of SSRIs are unique and are characterized by the presence of two well-defined conjugated spectra with maxima at 300 and 382 nm. Fluorimetry is very suitable for assessment of plasma SSRI levels. This inexpensive and efficient technique can objectively and reliably quantify drug levels in biological fluids, thereby directly determining the level of patient adherence to the prescribed drug regimen. This method will be useful in a broad spectrum of applications, from compliance/bioavailability assessments in animal and human experiments to utilization in large-scale clinical trials.

The GuideView System for Interactive, Structured, Multi-modal Delivery of Clinical Guidelines

NASA Technical Reports Server (NTRS)

Iyengar, Sriram; Florez-Arango, Jose; Garcia, Carlos Andres

2009-01-01

GuideView is a computerized clinical guideline system which delivers clinical guidelines in an easy-to-understand and easy-to-use package. It may potentially enhance the quality of medical care or allow non-medical personnel to provide acceptable levels of care in situations where physicians or nurses may not be available. Such a system can be very valuable during space flight missions when a physician is not readily available, or perhaps the designated medical personnel is unable to provide care. Complex clinical guidelines are broken into simple steps. At each step clinical information is presented in multiple modes, including voice,audio, text, pictures, and video. Users can respond via mouse clicks or via voice navigation. GuideView can also interact with medical sensors using wireless or wired connections. The system's interface is illustrated and the results of a usability study are presented.

Pulmonary Sporotrichosis: An Evolving Clinical Paradigm.

PubMed

Aung, Ar K; Spelman, Denis W; Thompson, Philip J

2015-10-01

In recent decades, sporotrichosis, caused by thermally dimorphic fungi Sporothrix schenckii complex, has become an emerging infection in many parts of the world. Pulmonary infection with S. schenckii still remains relatively uncommon, possibly due to underrecognition. Pulmonary sporotrichosis presents with distinct clinical and radiological patterns in both immunocompetent and immunocompromised hosts and can often result in significant morbidity and mortality despite treatment. Current understanding regarding S. schenckii biology, epidemiology, immunopathology, clinical diagnostics, and treatment options has been evolving in the recent years with increased availability of molecular sequencing techniques. However, this changing knowledge has not yet been fully translated into a better understanding of the clinical aspects of pulmonary sporotrichosis, as such current management guidelines remain unsupported by high-level clinical evidence. This article examines recent advances in the knowledge of sporotrichosis and its application to the difficult challenges of managing pulmonary sporotrichosis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Single and Multiple Clinical Syndromes in Incarcerated Offenders: Associations With Dissociative Experiences and Emotionality

PubMed Central

Garofalo, Carlo; Velotti, Patrizia; Crocamo, Cristina; Carrà, Giuseppe

2017-01-01

The present study examined the prevalence and correlates of clinical syndromes in a large group (N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically relevant symptoms for at least one clinical syndrome (n = 252), and the majority of them (38%) reported more syndromes in comorbidity (n = 169). Increased severity of clinical conditions (none, one, more than one syndrome) corresponded with significantly greater levels of personality disorder traits, psychological symptoms, dissociation, and negative emotionality, with large effect sizes. After controlling for co-occurrence of personality disorder traits and other symptoms, the presence of more than one comorbid syndrome significantly predicted unique variance in dissociation (positively) and positive emotionality (negatively). The presence of one clinical syndrome significantly and positively predicted negative emotionality. Findings support the possibility that the complexity, and not just the presence, of psychopathology could identify different groups of inmates. PMID:27913716

Single and Multiple Clinical Syndromes in Incarcerated Offenders: Associations With Dissociative Experiences and Emotionality.

PubMed

Garofalo, Carlo; Velotti, Patrizia; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

The present study examined the prevalence and correlates of clinical syndromes in a large group ( N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically relevant symptoms for at least one clinical syndrome ( n = 252), and the majority of them (38%) reported more syndromes in comorbidity ( n = 169). Increased severity of clinical conditions (none, one, more than one syndrome) corresponded with significantly greater levels of personality disorder traits, psychological symptoms, dissociation, and negative emotionality, with large effect sizes. After controlling for co-occurrence of personality disorder traits and other symptoms, the presence of more than one comorbid syndrome significantly predicted unique variance in dissociation (positively) and positive emotionality (negatively). The presence of one clinical syndrome significantly and positively predicted negative emotionality. Findings support the possibility that the complexity, and not just the presence, of psychopathology could identify different groups of inmates.

42 CFR 493.1453 - Condition: Laboratories performing high complexity testing; clinical consultant.

Code of Federal Regulations, 2010 CFR

2010-10-01

... testing; clinical consultant. 493.1453 Section 493.1453 Public Health CENTERS FOR MEDICARE & MEDICAID... Condition: Laboratories performing high complexity testing; clinical consultant. The laboratory must have a clinical consultant who meets the requirements of § 493.1455 of this subpart and provides clinical...

Patient safety competency and educational needs of nursing educators in South Korea

PubMed Central

2017-01-01

Background Nursing educators must be qualified to teach patient safety to nursing students to ensure patient safety in the clinical field. The purpose of this study was to assess nursing educators’ competencies and educational needs for patient safety in hospitals and nursing schools. Method A mixed-methods sequential explanatory design employed a survey and focus group interview with nursing educators (school clinical instructors and hospital nurse preceptors). Thirty-eight questionnaires filled out by clinical instructors from six four-year nursing universities and 106 questionnaires from nurse preceptors from three high-level general hospitals in the Seoul metropolitan area were analyzed to obtain quantitative data. Focus group interviews were conducted among six clinical instructors from one nursing school and four nurse preceptors from one high-level general hospital in Seoul. Results Nursing educators had higher levels of attitude compared with relatively lower levels of skill and knowledge regarding patient safety. They reported educational needs of “medication” and “infection prevention” as being higher and “human factors” and “complexity of systems” as being lower. Nursing educators desired different types of education for patient safety. Conclusion It is necessary to enhance nursing educators’ patient safety skills and knowledge by developing and providing an integrated program of patient safety, with various teaching methods to meet their educational needs. The findings of this study provide the basic information needed to reform patient safety education programs appropriately to fit nursing educators' needs and their patient safety competencies in both clinical practice and academia. Furthermore, the findings have revealed the importance of effective communication between clinical and academic settings in making patient safety education seamless. PMID:28873099

Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease.

PubMed

Rossi, Meghan; Mead, Simon; Collinge, John; Rudge, Peter; Vincent, Angela

2015-06-01

There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. This study indicates that <5% patients with sCJD develop serum antibodies to these neuronal antigens and, when positive, only at low titres. By contrast, three patients referred with possible prion disease had a clinical picture in keeping with autoimmune encephalitis and very high VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Development and Validation of the Pediatric Medical Complexity Algorithm (PMCA) Version 3.0.

PubMed

Simon, Tamara D; Haaland, Wren; Hawley, Katherine; Lambka, Karen; Mangione-Smith, Rita

2018-02-26

To modify the Pediatric Medical Complexity Algorithm (PMCA) to include both International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification (ICD-9/10-CM) codes for classifying children with chronic disease (CD) by level of medical complexity and to assess the sensitivity and specificity of the new PMCA version 3.0 for correctly identifying level of medical complexity. To create version 3.0, PMCA version 2.0 was modified to include ICD-10-CM codes. We applied PMCA version 3.0 to Seattle Children's Hospital data for children with ≥1 emergency department (ED), day surgery, and/or inpatient encounter from January 1, 2016, to June 30, 2017. Starting with the encounter date, up to 3 years of retrospective discharge data were used to classify children as having complex chronic disease (C-CD), noncomplex chronic disease (NC-CD), and no CD. We then selected a random sample of 300 children (100 per CD group). Blinded medical record review was conducted to ascertain the levels of medical complexity for these 300 children. The sensitivity and specificity of PMCA version 3.0 was assessed. PMCA version 3.0 identified children with C-CD with 86% sensitivity and 86% specificity, children with NC-CD with 65% sensitivity and 84% specificity, and children without CD with 77% sensitivity and 93% specificity. PMCA version 3.0 is an updated publicly available algorithm that identifies children with C-CD, who have accessed tertiary hospital emergency department, day surgery, or inpatient care, with very good sensitivity and specificity when applied to hospital discharge data and with performance to earlier versions of PMCA. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Functional interactions of HIV-infection and methamphetamine dependence during motor programming.

PubMed

Archibald, Sarah L; Jacobson, Mark W; Fennema-Notestine, Christine; Ogasawara, Miki; Woods, Steven P; Letendre, Scott; Grant, Igor; Jernigan, Terry L

2012-04-30

Methamphetamine (METH) dependence is frequently comorbid with HIV infection and both have been linked to alterations of brain structure and function. In a previous study, we showed that the brain volume loss characteristic of HIV infection contrasts with METH-related volume increases in striatum and parietal cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan et al., 2005). Functional magnetic resonance imaging (fMRI) has the potential to reveal functional interactions between the effects of HIV and METH. In the present study, 50 participants were studied in four groups: an HIV+ group, a recently METH-dependent group, a dually affected group, and a group of unaffected community comparison subjects. An fMRI paradigm consisting of motor sequencing tasks of varying levels of complexity was administered to examine blood oxygenation level dependent (BOLD) changes. Within all groups, activity increased significantly with increasing task complexity in large clusters within sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The task complexity effect was regressed on HIV status, METH status, and the HIV×METH interaction term in a simultaneous multiple regression. HIV was associated with less complexity-related activation in striatum, whereas METH was associated with less complexity-related activation in parietal regions. Significant interaction effects were observed in both cortical and subcortical regions; and, contrary to expectations, the complexity-related activation was less aberrant in dually affected than in single risk participants, in spite of comparable levels of neurocognitive impairment among the clinical groups. Thus, HIV and METH dependence, perhaps through their effects on dopaminergic systems, may have opposing functional effects on neural circuits involved in motor programming. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

Patients with triangular fibrocartilage complex injuries and distal radioulnar joint instability have reduced rotational torque in the forearm.

PubMed

Andersson, J K; Axelsson, P; Strömberg, J; Karlsson, J; Fridén, J

2016-09-01

A total of 20 patients scheduled for wrist arthroscopy, all with clinical signs of rupture to the triangular fibrocartilage complex and distal radioulnar joint instability, were tested pre-operatively by an independent observer for strength of forearm rotation. During surgery, the intra-articular pathology was documented by photography and also subsequently individually analysed by another independent hand surgeon. Arthroscopy revealed a type 1-B injury to the triangular fibrocartilage complex in 18 of 20 patients. Inter-rater reliability between the operating surgeon and the independent reviewer showed absolute agreement in all but one patient (95%) in terms of the injury to the triangular fibrocartilage complex and its classification. The average pre-operative torque strength was 71% of the strength of the non-injured contralateral side in pronation and supination. Distal radioulnar joint instability with an arthroscopically verified injury to the triangular fibrocartilage complex is associated with a significant loss of both pronation and supination torque. Case series, Level IV. © The Author(s) 2015.

From Anatomical "Competence" to Complex Capability. The Views and Experiences of UK Tutors on How We Should Teach Anatomy to Medical Students

ERIC Educational Resources Information Center

de Bere, Sam Regan; Mattick, Karen

2010-01-01

Developments in clinical education have recently challenged the identity of anatomy teaching and learning, leading to high profile debate over the potential implications for the competence levels of new doctors. However, the emphasis remains on methods of teaching, rather than a review of what well-rounded anatomical learning actually entails, and…

Adaptive optics for in-vivo exploration of human retinal structures

NASA Astrophysics Data System (ADS)

Paques, Michel; Meimon, Serge; Grieve, Kate; Rossant, Florence

2017-06-01

Adaptive optics (AO)-enhanced imaging of the retina is now reaching a level of technical maturity which fosters its expanding use in research and clinical centers in the world. By achieving wavelength-limited resolution it did not only allow a better observation of retinal substructures already visible by other means, it also broke anatomical frontiers such as individual photoreceptors or vessel walls. The clinical applications of AO-enhanced imaging has been slower than that of optical coherence tomography because of the combination of technical complexity, costs and the paucity of interpretative scheme of complex data. In several diseases, AO-enhanced imaging has already proven to provide added clinical value and quantitative biomarkers. Here, we will review some of the clinical applications of AO-enhanced en face imaging, and trace perspectives to improve its clinical pertinence in these applications. An interesting perspective is to document cell motion through time-lapse imaging such as during agerelated macular degeneration. In arterial hypertension, the possibility to measure parietal thickness and perform fine morphometric analysis is of interest for monitoring patients. In the near future, implementation of novel approaches and multimodal imaging, including in particular optical coherence tomography, will undoubtedly expand our imaging capabilities. Tackling the technical, scientific and medical challenges offered by high resolution imaging are likely to contribute to our rethinking of many retinal diseases, and, most importantly, may find applications in other areas of medicine.

What predicts performance during clinical psychology training?

PubMed

Scior, Katrina; Bradley, Caroline E; Potts, Henry W W; Woolf, Katherine; de C Williams, Amanda C

2014-06-01

While the question of who is likely to be selected for clinical psychology training has been studied, evidence on performance during training is scant. This study explored data from seven consecutive intakes of the UK's largest clinical psychology training course, aiming to identify what factors predict better or poorer outcomes. Longitudinal cross-sectional study using prospective and retrospective data. Characteristics at application were analysed in relation to a range of in-course assessments for 274 trainee clinical psychologists who had completed or were in the final stage of their training. Trainees were diverse in age, pre-training experience, and academic performance at A-level (advanced level certificate required for university admission), but not in gender or ethnicity. Failure rates across the three performance domains (academic, clinical, research) were very low, suggesting that selection was successful in screening out less suitable candidates. Key predictors of good performance on the course were better A-levels and better degree class. Non-white students performed less well on two outcomes. Type and extent of pre-training clinical experience on outcomes had varied effects on outcome. Research supervisor ratings emerged as global indicators and predicted nearly all outcomes, but may have been biased as they were retrospective. Referee ratings predicted only one of the seven outcomes examined, and interview ratings predicted none of the outcomes. Predicting who will do well or poorly in clinical psychology training is complex. Interview and referee ratings may well be successful in screening out unsuitable candidates, but appear to be a poor guide to performance on the course. © 2013 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of the British Psychological Society.

The Clinical Nurse Leader--new nursing role with global implications.

PubMed

Baernholdt, M; Cottingham, S

2011-03-01

This paper describes the development of the Clinical Nurse Leader (CNL ©) role and education, the CNL's impact and potential to improve quality globally. The need for clinical nurse leadership to improve the quality of health care systems while controlling costs is recognized in reports internationally. In the USA, a new nursing role, the CNL, was developed in response to such reports. CNLs are master's level nurse graduates (although not necessarily recruited from a nursing background) with the skills and knowledge to create change within complex systems and improve outcomes while they remain direct care providers. This innovative role can be adapted worldwide to improve the quality of health care systems. © 2010 The Authors. International Nursing Review © 2010 International Council of Nurses.

Addiction Science: Uncovering Neurobiological Complexity

PubMed Central

Volkow, N. D.; Baler, R. D.

2013-01-01

Until very recently addiction-research was limited by existing tools and strategies that were inadequate for studying the inherent complexity at each of the different phenomenological levels. However, powerful new tools (e.g., optogenetics and designer drug receptors) and high throughput protocols are starting to give researchers the potential to systematically interrogate “all” genes, epigenetic marks, and neuronal circuits. These advances, combined with imaging technologies (both for preclinical and clinical studies) and a paradigm shift towards open access have spurred an unlimited growth of datasets transforming the way we investigate the neurobiology of substance use disorders (SUD) and the factors that modulate risk and resilience. PMID:23688927

Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair

PubMed Central

Wu, Zhongqi-Phyllis; Washburn, Lorraine; Bilousova, Tina V.; Boudzinskaia, Maia; Escande-Beillard, Nathalie; Querubin, Jyes; Dang, Hoa; Xie, Cui-Wei; Tian, Jide; Kaufman, Daniel L.

2012-01-01

Mice deficient in classical major histocompatibility complex class I (MHCI) have aberrations in neurodevelopment. The consequences of up-regulated neuronal MHCI expression have not been examined. We found that transgenic C57Bl/6 mice that are engineered to express higher levels of self-Db on their CNS neurons have alterations in their hippocampal morphology and retinogeniculate projections, as well as impaired neurorepair responses. Thus, enhanced neuronal classical MHCI expression can lead to aberrations in neural circuitry and neurorepair. These findings complement a growing body of knowledge concerning the neurobiological activities of MHCI and may have potential clinical relevance. PMID:20950866

Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies.

PubMed

Janghra, Narinder; Morgan, Jennifer E; Sewry, Caroline A; Wilson, Francis X; Davies, Kay E; Muntoni, Francesco; Tinsley, Jonathon

2016-01-01

Duchenne muscular dystrophy is a severe and currently incurable progressive neuromuscular condition, caused by mutations in the DMD gene that result in the inability to produce dystrophin. Lack of dystrophin leads to loss of muscle fibres and a reduction in muscle mass and function. There is evidence from dystrophin-deficient mouse models that increasing levels of utrophin at the muscle fibre sarcolemma by genetic or pharmacological means significantly reduces the muscular dystrophy pathology. In order to determine the efficacy of utrophin modulators in clinical trials, it is necessary to accurately measure utrophin levels and other biomarkers on a fibre by fibre basis within a biopsy section. Our aim was to develop robust and reproducible staining and imaging protocols to quantify sarcolemmal utrophin levels, sarcolemmal dystrophin complex members and numbers of regenerating fibres within a biopsy section. We quantified sarcolemmal utrophin in mature and regenerating fibres and the percentage of regenerating muscle fibres, in muscle biopsies from Duchenne, the milder Becker muscular dystrophy and controls. Fluorescent immunostaining followed by image analysis was performed to quantify utrophin intensity and β-dystrogylcan and ɣ -sarcoglycan intensity at the sarcolemma. Antibodies to fetal and developmental myosins were used to identify regenerating muscle fibres allowing the accurate calculation of percentage regeneration fibres in the biopsy. Our results indicate that muscle biopsies from Becker muscular dystrophy patients have fewer numbers of regenerating fibres and reduced utrophin intensity compared to muscle biopsies from Duchenne muscular dystrophy patients. Of particular interest, we show for the first time that the percentage of regenerating muscle fibres within the muscle biopsy correlate with the clinical severity of Becker and Duchenne muscular dystrophy patients from whom the biopsy was taken. The ongoing development of these tools to quantify sarcolemmal utrophin and muscle regeneration in muscle biopsies will be invaluable for assessing utrophin modulator activity in future clinical trials.

Visualization of Global Disease Burden for the Optimization of Patient Management and Treatment.

PubMed

Schlee, Winfried; Hall, Deborah A; Edvall, Niklas K; Langguth, Berthold; Canlon, Barbara; Cederroth, Christopher R

2017-01-01

The assessment and treatment of complex disorders is challenged by the multiple domains and instruments used to evaluate clinical outcome. With the large number of assessment tools typically used in complex disorders comes the challenge of obtaining an integrative view of disease status to further evaluate treatment outcome both at the individual level and at the group level. Radar plots appear as an attractive visual tool to display multivariate data on a two-dimensional graphical illustration. Here, we describe the use of radar plots for the visualization of disease characteristics applied in the context of tinnitus, a complex and heterogeneous condition, the treatment of which has shown mixed success. Data from two different cohorts, the Swedish Tinnitus Outreach Project (STOP) and the Tinnitus Research Initiative (TRI) database, were used. STOP is a population-based cohort where cross-sectional data from 1,223 non-tinnitus and 933 tinnitus subjects were analyzed. By contrast, the TRI contained data from 571 patients who underwent various treatments and whose Clinical Global Impression (CGI) score was accessible to infer treatment outcome. In the latter, 34,560 permutations were tested to evaluate whether a particular ordering of the instruments could reflect better the treatment outcome measured with the CGI. Radar plots confirmed that tinnitus subtypes such as occasional and chronic tinnitus from the STOP cohort could be strikingly different, and helped appreciate a gender bias in tinnitus severity. Radar plots with greater surface areas were consistent with greater burden, and enabled a rapid appreciation of the global distress associated with tinnitus in patients categorized according to tinnitus severity. Permutations in the arrangement of instruments allowed to identify a configuration with minimal variance and maximized surface difference between CGI groups from the TRI database, thus affording a means of optimally evaluating the outcomes in individual patients. We anticipate such a tool to become a starting point for more sophisticated measures in clinical outcomes, applicable not only in the context of tinnitus but also in other complex diseases where the integration of multiple variables is needed for a comprehensive evaluation of treatment response.

Feasibility of Conducting Autism Biomarker Research in the Clinical Setting.

PubMed

Sices, Laura; Pawlowski, Katherine; Farfel, Laura; Phillips, Deirdre; Howe, Yamini; Cochran, David M; Choueiri, Roula; Forbes, Peter W; Brewster, Stephanie J; Frazier, Jean A; Neumeyer, Ann; Bridgemohan, Carolyn

2017-09-01

Recruitment and completion of research activities during regular clinical care has the potential to increase research participation in complex neurodevelopmental disorders. We evaluated the feasibility, and effect on clinical care, of conducting biomarker research within a subspecialty clinical visit for autism spectrum disorder (ASD). Children, aged 5 to 10 years, were recruited by providers in ASD clinics at 5 institutions. Biomarkers collected were growth measurements, head circumference, neurologic and dysmorphology examinations, digit ratio (2D:4D) measurement, and platelet serotonin and urinary melatonin sulfate excretion levels. Parents completed the Aberrant Behavior Checklist-Community and a medical/demographic questionnaire. Cognitive level was abstracted from the medical record. Parents and clinicians completed surveys on the effect of the study on the clinical visit. Eighty-three children and their caregivers participated. Factors limiting participation included difficulty reaching families by phone and parent concern about the study blood draw requirement. All children completed at least 4 of 7 planned research activities. Demographic factors, educational placement, and child behavior were not associated with completion of study activities. Lower nonverbal cognitive function was weakly associated with fewer activities completed. Forty-four percent of clinicians reported an effect of the research study on the clinical visit. However, neither parent-reported nor clinician-reported effect was associated with the degree of study activity completion. Recruiting study participants in the context of scheduled ASD clinical visits required significant effort. However, once recruited, participants completed most study activities, regardless of behavioral symptom severity. Research activities did not adversely affect the clinical visit.

Factors influencing organizational adoption and implementation of clinical genetic services.

PubMed

Hamilton, Alison B; Oishi, Sabine; Yano, Elizabeth M; Gammage, Cynthia E; Marshall, Nell J; Scheuner, Maren T

2014-03-01

We sought to identify characteristics of genetic services that facilitate or hinder adoption. We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities. Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test-ordering processes. Adoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.

Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: A randomized controlled clinical trial.

PubMed

Martins, Sérgio H L; Novaes, Arthur B; Taba, Mario; Palioto, Daniela B; Messora, Michel R; Reino, Danilo M; Souza, Sérgio L S

2017-07-01

This randomized controlled clinical trial evaluated the effects of an adjunctive single application of antimicrobial photodynamic therapy (aPDT) in Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis (SCP). In a split-mouth design, 20 patients with SCP were treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was applied in a single episode, using a diode laser and a phenothiazine photosensitizer. All patients were monitored until 90 days after surgical therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA hybridization at baseline, 60 and 150 days. Clinical and microbiological parameters were evaluated. In deep periodontal pockets depth (PPD ≥5 mm), Test Group presented a significantly higher decrease in PPD than Control Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated significantly less periodontal pathogens of red complex (Treponema denticola) (p < .05). A single episode of aPDT used in adjunct to open flap debridement of the root surface in the surgical treatment of SCP: i) significantly improved clinical periodontal parameters; ii) eliminates periodontal pathogens of the red complex more effectively (NCT02734784). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Single-Nucleotide Polymorphisms Identified in Clinical Samples Can Affect MicroRNA Processing, Level of Expression, and Silencing Activity

PubMed Central

Han, Soo-Jin; Marshall, Vickie; Barsov, Eugene; Quiñones, Octavio; Ray, Alex; Labo, Nazzarena; Trivett, Matthew; Ott, David; Renne, Rolf

2013-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs that can produce 25 KSHV mature microRNAs. We previously reported single-nucleotide polymorphisms (SNPs) in KSHV-encoded pre-microRNA and mature microRNA sequences from clinical samples (V. Marshall et al., J. Infect. Dis., 195:645–659, 2007). To determine whether microRNA SNPs affect pre-microRNA processing and, ultimately, mature microRNA expression levels, we performed a detailed comparative analysis of (i) mature microRNA expression levels, (ii) in vitro Drosha/Dicer processing, and (iii) RNA-induced silencing complex-dependent targeting of wild-type (wt) and variant microRNA genes. Expression of pairs of wt and variant pre-microRNAs from retroviral vectors and measurement of KSHV mature microRNA expression by real-time reverse transcription-PCR (RT-PCR) revealed differential expression levels that correlated with the presence of specific sequence polymorphisms. Measurement of KSHV mature microRNA expression in a panel of primary effusion lymphoma cell lines by real-time RT-PCR recapitulated some observed expression differences but suggested a more complex relationship between sequence differences and expression of mature microRNA. Furthermore, in vitro maturation assays demonstrated significant SNP-associated changes in Drosha/DGCR8 and/or Dicer processing. These data demonstrate that SNPs within KSHV-encoded pre-microRNAs are associated with differential microRNA expression levels. Given the multiple reports on the involvement of microRNAs in cancer, the biological significance of these phenotypic and genotypic variants merits further studies in patients with KSHV-associated malignancies. PMID:24006441

The objective structured clinical examination revisited for postgraduate trainees in general practice.

PubMed

Schoenmakers, Birgitte; Wens, Johan

2014-03-04

To investigate if the psychometric qualities of an OSCE consisting of more complex simulated patient encounters remain valid and reliable in the assessment of postgraduate trainees in general practice. In this intervention study without control group, the traditional OSCE was formally replaced by the new, complex version. The study population was composed by all postgraduate trainees (second and third phase) in general practice during the ongoing academic year. Data were handled and collected as part of the formal assessment program. Univariate analyses, the variance of scores and multivariate analyses were performed to assess the test qualities. A total of 340 students participated. Average final scores were slightly higher for third-phase students (t-test, p =0.05). Overall test scores were equally distributed on station level, circuit level and phase level. A multiple regression analysis revealed that test scores were dependent on the stations and circuits, but not on the master phase. In a changing learning environment, assessment and evaluation strategies require reorientation. The reliability and validity of the OSCE remain subject to discussion. In particular, when it comes to content and design, the traditional OSCE might underestimate the performance level of postgraduate trainees in general practice. A reshaping of this OSCE to a more sophisticated design with more complex patient encounters appears to restore the validity of the test results.

A novel approach to the use of subgingival controlled-release chlorhexidine delivery in chronic periodontitis: a randomized clinical trial.

PubMed

Gonzales, Jose R; Harnack, Lutz; Schmitt-Corsitto, Gabriella; Boedeker, Rolf H; Chakraborty, Trinad; Domann, Eugen; Meyle, Joerg

2011-08-01

We aimed to analyze clinical, microbiologic, and serologic effects of chlorhexidine (CHX) chips used as a subgingival controlled-release delivery device before and immediately after scaling and root planing (SRP). Twenty-four patients presenting with ≥12 teeth with probing depth (PD) ≥5 mm and bleeding on probing were assigned in test or control groups. After prophylaxis, CHX chips (test) or placebo chips (control) were placed in pockets with PD ≥5 mm. Ten days later, SRP was performed in all teeth with PD ≥4 mm in a single appointment. Immediately after SRP, new chips were inserted in all pockets with PD ≥5 mm. Parameters were assessed at baseline; beginning of SRP; and 1, 3, and 6 months after treatment. Subgingival samples were obtained at baseline; beginning of SRP; and at 1 month after treatment. Periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola were analyzed. Serum levels of high sensitive C-reactive and lipopolysaccharide-binding proteins were measured. The changes of the parameters between and within the groups were tested by Mann-Whitney U test (P <0.05). All clinical and serologic parameters improved in both groups over time. There was a significant difference in clinical attachment level (CAL) gain from baseline to 6 months between groups (1.17 mm in the test group versus 0.79 mm in the placebo group) (P <0.05). The treatment with CHX chips showed a greater reduction of the microorganisms of the "red complex" after 1 month (P = 0.02). The use of CHX chips before and immediately after SRP improved CAL and reduced the subgingival microorganisms of the red complex in the treatment of chronic periodontitis.

Sense and readability: participant information sheets for research studies.

PubMed

Ennis, Liam; Wykes, Til

2016-02-01

Informed consent in research is partly achieved through the use of information sheets. There is a perception however that these information sheets are long and complex. The recommended reading level for patient information is grade 6, or 11-12 years old. To investigate whether the readability of participant information sheets has changed over time, whether particular study characteristics are related to poorer readability and whether readability and other study characteristics are related to successful study recruitment. Method: We obtained 522 information sheets from the UK National Institute for Health Research Clinical Research Network: Mental Health portfolio database and study principal investigators. Readability was assessed with the Flesch reading index and the Grade level test. Information sheets increased in length over the study period. The mean grade level across all information sheets was 9.8, or 15-16 years old. A high level of patient involvement was associated with more recruitment success and studies involving pharmaceutical or device interventions were the least successful. The complexity of information sheets had little bearing on successful recruitment. Information sheets are far more complex than the recommended reading level of grade 6 for patient information. The disparity may be exacerbated by an increasing focus on legal content. Researchers would benefit from clear guidance from ethics committees on writing succinctly and accessibly and how to balance the competing legal issues with the ability of participants to understand what a study entails. © The Royal College of Psychiatrists 2016.

Sense and readability: participant information sheets for research studies

PubMed Central

Ennis, Liam; Wykes, Til

2016-01-01

Background Informed consent in research is partly achieved through the use of information sheets. There is a perception however that these information sheets are long and complex. The recommended reading level for patient information is grade 6, or 11–12 years old. Aims To investigate whether the readability of participant information sheets has changed over time, whether particular study characteristics are related to poorer readability and whether readability and other study characteristics are related to successful study recruitment. Method We obtained 522 information sheets from the UK National Institute for Health Research Clinical Research Network: Mental Health portfolio database and study principal investigators. Readability was assessed with the Flesch reading index and the Grade level test. Results Information sheets increased in length over the study period. The mean grade level across all information sheets was 9.8, or 15–16 years old. A high level of patient involvement was associated with more recruitment success and studies involving pharmaceutical or device interventions were the least successful. The complexity of information sheets had little bearing on successful recruitment. Conclusions Information sheets are far more complex than the recommended reading level of grade 6 for patient information. The disparity may be exacerbated by an increasing focus on legal content. Researchers would benefit from clear guidance from ethics committees on writing succinctly and accessibly and how to balance the competing legal issues with the ability of participants to understand what a study entails. PMID:26382948

Relationship of Mitochondrial Enzymes to Fatigue Intensity in Men With Prostate Cancer Receiving External Beam Radiation Therapy

PubMed Central

Filler, Kristin; Lyon, Debra; McCain, Nancy; Bennett, James; Fernández-Martínez, Juan Luis; deAndrés-Galiana, Enrique Juan; Elswick, R. K.; Lukkahatai, Nada; Saligan, Leorey

2015-01-01

Purpose: Mitochondrial dysfunction is a plausible biological mechanism for cancer-related fatigue. Specific aims of this study were to (1) describe the levels of mitochondrial oxidative phosphorylation complex (MOPC) enzymes, fatigue, and health-related quality of life (HRQOL) before and at completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (PC); (2) examine relationships over time among levels of MOPC enzymes, fatigue, and HRQOL; and (3) compare levels of MOPC enzymes in men with clinically significant and nonsignificant fatigue intensification during EBRT. Methods: Fatigue was measured by the revised Piper Fatigue Scale and the Functional Assessment of Cancer Therapy–Fatigue subscale (FACT-F). MOPC enzymes (Complexes I–V) and mitochondrial antioxidant superoxide dismutase 2 were measured in peripheral blood using enzyme-linked immunosorbent assay at baseline and completion of EBRT. Participants were categorized into high or low fatigue (HF vs. LF) intensification groups based on amount of change in FACT-F scores during EBRT. Results: Fatigue reported by the 22 participants with PC significantly worsened and HRQOL significantly declined from baseline to EBRT completion. The HF group comprised 12 men with clinically significant change in fatigue (HF) during EBRT. Although no significant changes were observed in MOPC enzymes from baseline to EBRT completion, there were important differences in the patterns in the levels of MOPC enzymes between HF and LF groups. Conclusion: Distinct patterns of changes in the absorbance of MOPC enzymes delineated fatigue intensification among participants. Further investigation using a larger sample is warranted. PMID:26584846

Mapping of interaction domains between human repair proteins ERCC1 and XPF.

PubMed

de Laat, W L; Sijbers, A M; Odijk, H; Jaspers, N G; Hoeijmakers, J H

1998-09-15

ERCC1-XPF is a heterodimeric protein complexinvolved in nucleotide excision repair and recombinational processes. Like its homologous complex in Saccharomyces cerevisiae , Rad10-Rad1, it acts as a structure-specific DNA endonuclease, cleaving at duplex-single-stranded DNA junctions. In repair, ERCC1-XPF and Rad10-Rad1 make an incision on the the 5'-side of the lesion. No humans with a defect in the ERCC1 subunit of this protein complex have been identified and ERCC1-deficient mice suffer from severe developmental problems and signs of premature aging on top of a repair-deficient phenotype. Xeroderma pigmentosum group F patients carry mutations in the XPF subunit and generally show the clinical symptoms of mild DNA repair deficiency. All XP-F patients examined demonstrate reduced levels of XPF and ERCC1 protein, suggesting that proper complex formation is required for stability of the two proteins. To better understand the molecular and clinical consequences of mutations in the ERCC1-XPF complex, we decided to map the interaction domains between the two subunits. The XPF-binding domain comprises C-terminal residues 224-297 of ERCC1. Intriguingly, this domain resides outside the region of homology with its yeast Rad10 counterpart. The ERCC1-binding domain in XPF maps to C-terminal residues 814-905. ERCC1-XPF complex formation is established by a direct interaction between these two binding domains. A mutation from an XP-F patient that alters the ERCC1-binding domain in XPF indeed affects complex formation with ERCC1.

Mapping of interaction domains between human repair proteins ERCC1 and XPF.

PubMed Central

de Laat, W L; Sijbers, A M; Odijk, H; Jaspers, N G; Hoeijmakers, J H

1998-01-01

ERCC1-XPF is a heterodimeric protein complexinvolved in nucleotide excision repair and recombinational processes. Like its homologous complex in Saccharomyces cerevisiae , Rad10-Rad1, it acts as a structure-specific DNA endonuclease, cleaving at duplex-single-stranded DNA junctions. In repair, ERCC1-XPF and Rad10-Rad1 make an incision on the the 5'-side of the lesion. No humans with a defect in the ERCC1 subunit of this protein complex have been identified and ERCC1-deficient mice suffer from severe developmental problems and signs of premature aging on top of a repair-deficient phenotype. Xeroderma pigmentosum group F patients carry mutations in the XPF subunit and generally show the clinical symptoms of mild DNA repair deficiency. All XP-F patients examined demonstrate reduced levels of XPF and ERCC1 protein, suggesting that proper complex formation is required for stability of the two proteins. To better understand the molecular and clinical consequences of mutations in the ERCC1-XPF complex, we decided to map the interaction domains between the two subunits. The XPF-binding domain comprises C-terminal residues 224-297 of ERCC1. Intriguingly, this domain resides outside the region of homology with its yeast Rad10 counterpart. The ERCC1-binding domain in XPF maps to C-terminal residues 814-905. ERCC1-XPF complex formation is established by a direct interaction between these two binding domains. A mutation from an XP-F patient that alters the ERCC1-binding domain in XPF indeed affects complex formation with ERCC1. PMID:9722633

Setting performance standards for medical practice: a theoretical framework.

PubMed

Southgate, L; Hays, R B; Norcini, J; Mulholland, H; Ayers, B; Woolliscroft, J; Cusimano, M; McAvoy, P; Ainsworth, M; Haist, S; Campbell, M

2001-05-01

The assessment of performance in the real world of medical practice is now widely accepted as the goal of assessment at the postgraduate level. This is largely a validity issue, as it is recognised that tests of knowledge and in clinical simulations cannot on their own really measure how medical practitioners function in the broader health care system. However, the development of standards for performance-based assessment is not as well understood as in competency assessment, where simulations can more readily reflect narrower issues of knowledge and skills. This paper proposes a theoretical framework for the development of standards that reflect the more complex world in which experienced medical practitioners work. The paper reflects the combined experiences of a group of education researchers and the results of literature searches that included identifying current health system data sources that might contribute information to the measurement of standards. Standards that reflect the complexity of medical practice may best be developed through an "expert systems" analysis of clinical conditions for which desired health care outcomes reflect the contribution of several health professionals within a complex, three-dimensional, contextual model. Examples of the model are provided, but further work is needed to test validity and measurability.

Congenital heart disease: interrelation between German diagnosis-related groups system and Aristotle complexity score.

PubMed

Sinzobahamvya, Nicodème; Photiadis, Joachim; Arenz, Claudia; Kopp, Thorsten; Hraska, Viktor; Asfour, Boulos

2010-06-01

The Disease-Related Groups (DRGs) system postulates that inpatient stays with similar levels of clinical complexity are expected to consume similar amounts of resources. This, applied to surgery of congenital heart disease, suggests that the higher the complexity of procedures as estimated by the Aristotle complexity score, the higher hospital reimbursement should be. This study analyses how much case-mix index (CMI) generated by German DRG 2009 version correlates with Aristotle score. A total of 456 DRG cases of year 2008 were regrouped according to German DRG 2009 and related cost-weight values and overall CMI evaluated. Corresponding Aristotle basic and comprehensive complexity scores (ABC and ACC) and levels were determined. Associated surgical performance (Aristotle score times hospital survival) was estimated. Spearman 'r' correlation coefficients were calculated between Aristotle scores and cost-weights. Goodness of fit 'r(2)' from derived regression was determined. Correlation was estimated to be optimal if Spearman 'r' and derived goodness of fit 'r(2)' approached 1 value. CMI was 8.787 while mean ABC and ACC scores were 7.64 and 9.27, respectively. Hospital survival was 98.5%: therefore, surgical performance attained 7.53 (ABC score) and 9.13 (ACC score). ABC and ACC scores and levels positively correlated with cost-weights. With Spearman 'r' of 1 and goodness of fit 'r(2)' of 0.9790, scores of the six ACC levels correlated at best. The equation was y = 0.5591 + 0.939x, in which y stands for cost-weight (CMI) and x for score of ACC level. ACC score correlates almost perfectly with corresponding cost-weights (CMI) generated by the German DRG 2009. It could therefore be used as the basis for hospital reimbursement to compensate in conformity with procedures' complexity. Extrapolated CMI in this series would be 9.264. Modulation of reimbursement according to surgical performance could be established and thus 'reward' quality in congenital heart surgery. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Supportive Care Treatment Guidelines: Value, Limitations, and Opportunities

PubMed Central

Peterson, Douglas E.; Bensadoun, Rene-Jean; Lalla, Rajesh V.; McGuire, Deborah B.

2013-01-01

Evidence-based guidelines in clinical oncology practice are now prominent, with emphasis on clinical, health outcome and economic perspectives. Given the complexity of cancer management, a multidisciplinary approach is essential. Evidence-based guidelines to address supportive cancer care have merged expert opinion, systematic evaluation of clinical and research data, and meta-analyses of clinical trials. Production of supportive care guidelines by the interdisciplinary team is dependent on sufficient high-quality research studies. Once published, it is essential they be customized at institutional and national levels. Implementation in clinical practice is perhaps the greatest challenge. Optimal management occurs through integration of country-specific issues, including care access, healthcare resources, information technology, and national coordination of healthcare practices. The purpose of this article is to: (1) provide an overview of interdisciplinary cancer management using evidence-based guidelines; (2) delineate the theory and practice of guideline dissemination, utilization and outcome assessment; and (3) recommend future research strategies to maximize guidelines use in clinical practice. PMID:21600365

Factors influencing practice variation in the management of nephrotic syndrome: a qualitative study of pediatric nephrology care providers

PubMed Central

Samuel, Susan M.; Flynn, Rachel; Zappitelli, Michael; Dart, Allison; Parekh, Rulan; Pinsk, Maury; Mammen, Cherry; Wade, Andrew; Scott, Shannon D.

2017-01-01

Background: Treatment protocols for childhood nephrotic syndrome are highly variable between providers and care centres. We conducted a qualitative study to understand the complex multilevel processes that lead to practice variation and influence provider management of nephrotic syndrome. Methods: Focus groups with multidisciplinary pediatric nephrology care providers (n = 67) from 10 Canadian pediatric nephrology centres that had more than 1 pediatric nephrologist were conducted between September 2013 and April 2015. Focus group discussions were guided by the Ottawa Model for Research Use. We used a semistructured interview guide to elicit participants' perspectives regarding 1) the work setting and context of the clinical environment, 2) reasons for variation at the provider level and 3) clinical practice guidelines for nephrotic syndrome. Focus group discussions were transcribed and analyzed concurrently with the use of qualitative content analysis. Results: Emerging themes were grouped into 2 categories: centre-level factors and provider-level factors. At the centre level, the type of care model used, clinic structures and resources, and lack of communication and collaboration within and between Canadian centres influenced care variation. At the provider level, use of experiential knowledge versus empirical knowledge and interpretation of patient characteristics influenced provider management of nephrotic syndrome. Interpretation: Centre- and provider-level factors play an important role in shaping practice differences in the management of childhood nephrotic syndrome. Further research is needed to determine whether variation in care is associated with disparities in outcomes. PMID:28592406

The genome sequence of 'Mycobacterium massiliense' strain CIP 108297 suggests the independent taxonomic status of the Mycobacterium abscessus complex at the subspecies level.

PubMed

Cho, Yong-Joon; Yi, Hana; Chun, Jongsik; Cho, Sang-Nae; Daley, Charles L; Koh, Won-Jung; Shin, Sung Jae

2013-01-01

Members of the Mycobacterium abscessus complex are rapidly growing mycobacteria that are emerging as human pathogens. The M. abscessus complex was previously composed of three species, namely M. abscessus sensu stricto, 'M. massiliense', and 'M. bolletii'. In 2011, 'M. massiliense' and 'M. bolletii' were united and reclassified as a single subspecies within M. abscessus: M. abscessus subsp. bolletii. However, the placement of 'M. massiliense' within the boundary of M. abscessus subsp. bolletii remains highly controversial with regard to clinical aspects. In this study, we revisited the taxonomic status of members of the M. abscessus complex based on comparative analysis of the whole-genome sequences of 53 strains. The genome sequence of the previous type strain of 'Mycobacterium massiliense' (CIP 108297) was determined using next-generation sequencing. The genome tree based on average nucleotide identity (ANI) values supported the differentiation of 'M. bolletii' and 'M. massiliense' at the subspecies level. The genome tree also clearly illustrated that 'M. bolletii' and 'M. massiliense' form a distinct phylogenetic clade within the radiation of the M. abscessus complex. The genomic distances observed in this study suggest that the current M. abscessus subsp. bolletii taxon should be divided into two subspecies, M. abscessus subsp. massiliense subsp. nov. and M. abscessus subsp. bolletii, to correspondingly accommodate the previously known 'M. massiliense' and 'M. bolletii' strains.

Anesthesia Practice and Clinical Trends in Interventional Radiology: A European Survey

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

Haslam, Philip J.; Yap, Bernard; Mueller, Peter R.

Purpose: To determine current European practice in interventional radiology regarding nursing care, anesthesia, and clinical care trends.Methods: A survey was sent to 977 European interventional radiologists to assess the use of sedoanalgesia, nursing care, monitoring equipment, pre- and postprocedural care, and clinical trends in interventional radiology. Patterns of sedoanalgesia were recorded for both vascular and visceral interventional procedures. Responders rated their preferred level of sedoanalgesia for each procedure as follows: (a) awake/alert, (b) drowsy/arousable, (c) asleep/arousable, (d) deep sedation, and (e) general anesthesia. Sedoanalgesic drugs and patient care trends were also recorded. A comparison was performed with data derived frommore » a similar survey of interventional practice in the United States.Results: Two hundred and forty-three of 977 radiologists responded (25%). The total number of procedures analyzed was 210,194. The majority (56%) of diagnostic and therapeutic vascular procedures were performed at the awake/alert level of sedation, 32% were performed at the drowsy/arousable level, and 12% at deeper levels of sedation. The majority of visceral interventional procedures were performed at the drowsy/arousable level of sedation (41%), 29% were performed at deeper levels of sedation, and 30% at the awake/alert level. In general, more sedoanalgesia is used in the United States. Eighty-three percent of respondents reported the use of a full-time radiology nurse, 67% used routine blood pressure/pulse oximetry monitoring, and 46% reported the presence of a dedicated recovery area. Forty-nine percent reported daily patient rounds, 30% had inpatient hospital beds, and 51% had day case beds.Conclusion: This survey shows clear differences in the use of sedation for vascular and visceral interventional procedures. Many, often complex, procedures are performed at the awake/alert level of sedation in Europe, whereas deeper levels of sedation are used in the United States. Trends toward making interventional radiology a clinical specialty are evident, with 51% of respondents having day case beds, and 30% having inpatient beds.« less

Obesity-specific neural cost of maintaining gait performance under complex conditions in community-dwelling older adults.

PubMed

Osofundiya, Olufunmilola; Benden, Mark E; Dowdy, Diane; Mehta, Ranjana K

2016-06-01

Recent evidence of obesity-related changes in the prefrontal cortex during cognitive and seated motor activities has surfaced; however, the impact of obesity on neural activity during ambulation remains unclear. The purpose of this study was to determine obesity-specific neural cost of simple and complex ambulation in older adults. Twenty non-obese and obese individuals, 65years and older, performed three tasks varying in the types of complexity of ambulation (simple walking, walking+cognitive dual-task, and precision walking). Maximum oxygenated hemoglobin, a measure of neural activity, was measured bilaterally using a portable functional near infrared spectroscopy system, and gait speed and performance on the complex tasks were also obtained. Complex ambulatory tasks were associated with ~2-3.5 times greater cerebral oxygenation levels and ~30-40% slower gait speeds when compared to the simple walking task. Additionally, obesity was associated with three times greater oxygenation levels, particularly during the precision gait task, despite obese adults demonstrating similar gait speeds and performances on the complex gait tasks as non-obese adults. Compared to existing studies that focus solely on biomechanical outcomes, the present study is one of the first to examine obesity-related differences in neural activity during ambulation in older adults. In order to maintain gait performance, obesity was associated with higher neural costs, and this was augmented during ambulatory tasks requiring greater precision control. These preliminary findings have clinical implications in identifying individuals who are at greater risk of mobility limitations, particularly when performing complex ambulatory tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accurate and Practical Identification of 20 Fusarium Species by Seven-Locus Sequence Analysis and Reverse Line Blot Hybridization, and an In Vitro Antifungal Susceptibility Study▿†

PubMed Central

Wang, He; Xiao, Meng; Kong, Fanrong; Chen, Sharon; Dou, Hong-Tao; Sorrell, Tania; Li, Ruo-Yu; Xu, Ying-Chun

2011-01-01

Eleven reference and 25 clinical isolates of Fusarium were subject to multilocus DNA sequence analysis to determine the species and haplotypes of the fusarial isolates from Beijing and Shandong, China. Seven loci were analyzed: the translation elongation factor 1 alpha gene (EF-1α); the nuclear rRNA internal transcribed spacer (ITS), large subunit (LSU), and intergenic spacer (IGS) regions; the second largest subunit of the RNA polymerase gene (RPB2); the calmodulin gene (CAM); and the mitochondrial small subunit (mtSSU) rRNA gene. We also evaluated an IGS-targeted PCR/reverse line blot (RLB) assay for species/haplotype identification of Fusarium. Twenty Fusarium species and seven species complexes were identified. Of 25 clinical isolates (10 species), the Gibberella (Fusarium) fujikuroi species complex was the commonest (40%) and was followed by the Fusarium solani species complex (FSSC) (36%) and the F. incarnatum-F. equiseti species complex (12%). Six FSSC isolates were identified to the species level as FSSC-3+4, and three as FSSC-5. Twenty-nine IGS, 27 EF-1α, 26 RPB2, 24 CAM, 18 ITS, 19 LSU, and 18 mtSSU haplotypes were identified; 29 were unique, and haplotypes for 24 clinical strains were novel. By parsimony informative character analysis, the IGS locus was the most phylogenetically informative, and the rRNA gene regions were the least. Results by RLB were concordant with multilocus sequence analysis for all isolates. Amphotericin B was the most active drug against all species. Voriconazole MICs were high (>8 μg/ml) for 15 (42%) isolates, including FSSC. Analysis of larger numbers of isolates is required to determine the clinical utility of the seven-locus sequence analysis and RLB assay in species classification of fusaria. PMID:21389150

Pulp Inflammation Diagnosis from Clinical to Inflammatory Mediators: A Systematic Review.

PubMed

Zanini, Marjorie; Meyer, Elisabeth; Simon, Stéphane

2017-07-01

Similar to other tissues, the dental pulp mounts an inflammatory reaction as a way to eliminate pathogens and stimulate repair. Pulp inflammation is prerequisite for dentin pulp complex repair and regeneration; otherwise, chronic disease or pulp necrosis occurs. Evaluation of pulp inflammation severity is necessary to predict the clinical success of maintaining pulp vitality. Clinical limitations to evaluating in situ inflammatory status are well-described. A molecular approach that aids clinical distinction between reversible and irreversible pulpitis could improve the success rate of vital pulp therapy. The aim of this article is to review inflammatory mediator expression in the context of clinical diagnosis. We searched PubMed and Cochrane databases for articles published between 1970 and December 2016. Only published studies of inflammatory mediator expression related to clinical diagnosis were eligible for inclusion and analysis. Thirty-two articles were analyzed. Two molecular approaches were described by study methods, protein expression analysis and gene expression analysis. Our review indicates that interleukin-8, matrix metalloproteinase 9, tumor necrosis factor-α, and receptor for advanced glycation end products expression increase at both the gene and protein levels during inflammation. Clinical irreversible pulpitis is related to specific levels of inflammatory mediator expression. The difference in expression between reversible and irreversible disease is both quantitative and qualitative. On the basis of our analysis, in situ quantification of inflammatory mediators may aid in the clinical distinction between reversible and irreversible pulpitis. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Laboratory diagnosis of von Willebrand's disease.

PubMed

Rick, M E

1994-12-01

The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given.

Case acceptance: no random acts allowed.

PubMed

McAnally, James

2009-12-01

Consider implementing a case acceptance system in your office to fully utilize your hard-earned clinical skills, and to experience the professional rewards that come with serving more patients at a higher level. Doctors who are willing to commit the time and resources necessary to improving case acceptance will increase the number of implant cases entering the treatment phase--cases that run the gamut of complexity and support fees commensurate with their skills!

Convolving engineering and medical pedagogies for training of tomorrow's health care professionals.

PubMed

Lee, Raphael C

2013-03-01

Several fundamental benefits justify why biomedical engineering and medicine should form a more convergent alliance, especially for the training of tomorrow's physicians and biomedical engineers. Herein, we review the rationale underlying the benefits. Biological discovery has advanced beyond the era of molecular biology well into today's era of molecular systems biology, which focuses on understanding the rules that govern the behavior of complex living systems. This has important medical implications. To realize cost-effective personalized medicine, it is necessary to translate the advances in molecular systems biology to higher levels of biological organization (organ, system, and organismal levels) and then to develop new medical therapeutics based on simulation and medical informatics analysis. Higher education in biological and medical sciences must adapt to a new set of training objectives. This will involve a shifting away from reductionist problem solving toward more integrative, continuum, and predictive modeling approaches which traditionally have been more associated with engineering science. Future biomedical engineers and MDs must be able to predict clinical response to therapeutic intervention. Medical education will involve engineering pedagogies, wherein basic governing rules of complex system behavior and skill sets in manipulating these systems to achieve a practical desired outcome are taught. Similarly, graduate biomedical engineering programs will include more practical exposure to clinical problem solving.

The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

PubMed

Ferreyra Solari, Nazarena E; Belforte, Fiorella S; Canedo, Lucía; Videla-Richardson, Guillermo A; Espinosa, Joaquín M; Rossi, Mario; Serna, Eva; Riudavets, Miguel A; Martinetto, Horacio; Sevlever, Gustavo; Perez-Castro, Carolina

2016-09-15

KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. Cancer Res; 76(18); 5383-94. ©2016 AACR. ©2016 American Association for Cancer Research.

The Paradox of Pelvic Exenteration: The Interaction of Clinical and Psychological Variables.

PubMed

Arnaboldi, Paola; Santoro, Luigi; Mazzocco, Ketti; Oliveri, Serena; Maggioni, Angelo; Pravettoni, Gabriella

2015-10-01

To text the feasibility of a psychological intervention package administered to 49 pelvic exenteration candidates, aimed at evaluating the preoperative prevalence of psychological distress and assessing the presence of any correlation between preoperative psychological distress and clinical variables such as pain and hospitalization length. Patients were referred to the psychology unit from the very beginning of their clinical pathway and were administered the Psychological Distress Inventory (PDI) and the Mini-Mental Adjustment to Cancer (Mini-MAC) questionnaire at prehospital admission. Patients presenting with a significant level of distress received nonstandardized psychological support. Statistical analyses were performed to detect the presence of any correlation between psychological variables at prehospital admission and clinical outcomes. The 40% of patients had significant levels of distress at prehospital admission (PDI ≥ 30). As regards Mini-MAC, the mean value of fighting spirit attitude and fatalism was higher in our sample than in the normative sample of the Mini-MAC validation study in the Italian cancer population. Their anxious preoccupation attitude was lower. There were no correlations between clinical and psychological variables: level of postsurgery pain was higher (3.7) in the subgroup of patients with presurgery PDI < 30 compared with those with PDI ≥ 30 (3.5). However, this difference was not statistically significant (P = 1.00). Considering hospitalization length, the above described trend was similar. Although highly distressed, pelvic exenteration candidates show an adaptive range of coping mechanisms. This calls for a greater effort in studying the complexity of their psychoemotional status to provide them with the best multidisciplinary care. Extensive study of the real effectiveness of psychological intervention is warranted: randomized clinical trials could help in detecting the presence of any correlation between clinical and psychological variables in a multidisciplinary approach.

The importance of relational coordination and reciprocal learning for chronic illness care within primary care teams.

PubMed

Noël, Polly Hitchcock; Lanham, Holly J; Palmer, Ray F; Leykum, Luci K; Parchman, Michael L

2013-01-01

Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with Type 2 diabetes in small primary care practices. Practice members (i.e., physicians, nonphysician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics and tested for mediation effects. A total of 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p < .01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual- and practice-level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members.

The Importance of Relational Coordination and Reciprocal Learning for Chronic Illness Care within Primary Care Teams

PubMed Central

Noël, Polly Hitchcock; Lanham, Holly J.; Palmer, Ray F.; Leykum, Luci K.; Parchman, Michael L.

2012-01-01

Background Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Purposes Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. Methodology/Approach We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with type 2 diabetes in small primary care practices. Practice members (i.e., physicians, non-physician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics, and tested for mediation effects. Findings 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p<.01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual and practice level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Practice Implications Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members. PMID:22310483

Coding OSICS sports injury diagnoses in epidemiological studies: does the background of the coder matter?

PubMed

Finch, Caroline F; Orchard, John W; Twomey, Dara M; Saad Saleem, Muhammad; Ekegren, Christina L; Lloyd, David G; Elliott, Bruce C

2014-04-01

To compare Orchard Sports Injury Classification System (OSICS-10) sports medicine diagnoses assigned by a clinical and non-clinical coder. Assessment of intercoder agreement. Community Australian football. 1082 standardised injury surveillance records. Direct comparison of the four-character hierarchical OSICS-10 codes assigned by two independent coders (a sports physician and an epidemiologist). Adjudication by a third coder (biomechanist). The coders agreed on the first character 95% of the time and on the first two characters 86% of the time. They assigned the same four-digit OSICS-10 code for only 46% of the 1082 injuries. The majority of disagreements occurred for the third character; 85% were because one coder assigned a non-specific 'X' code. The sports physician code was deemed correct in 53% of cases and the epidemiologist in 44%. Reasons for disagreement included the physician not using all of the collected information and the epidemiologist lacking specific anatomical knowledge. Sports injury research requires accurate identification and classification of specific injuries and this study found an overall high level of agreement in coding according to OSICS-10. The fact that the majority of the disagreements occurred for the third OSICS character highlights the fact that increasing complexity and diagnostic specificity in injury coding can result in a loss of reliability and demands a high level of anatomical knowledge. Injury report form details need to reflect this level of complexity and data management teams need to include a broad range of expertise.

Auditory dysfunction in schizophrenia: integrating clinical and basic features

PubMed Central

Javitt, Daniel C.; Sweet, Robert A.

2015-01-01

Schizophrenia is a complex neuropsychiatric disorder that is associated with persistent psychosocial disability in affected individuals. Although studies of schizophrenia have traditionally focused on deficits in higher-order processes such as working memory and executive function, there is an increasing realization that, in this disorder, deficits can be found throughout the cortex and are manifest even at the level of early sensory processing. These deficits are highly amenable to translational investigation and represent potential novel targets for clinical intervention. Deficits, moreover, have been linked to specific structural abnormalities in post-mortem auditory cortex tissue from individuals with schizophrenia, providing unique insights into underlying pathophysiological mechanisms. PMID:26289573

Supporting temporal queries on clinical relational databases: the S-WATCH-QL language.

PubMed Central

Combi, C.; Missora, L.; Pinciroli, F.

1996-01-01

Due to the ubiquitous and special nature of time, specially in clinical datábases there's the need of particular temporal data and operators. In this paper we describe S-WATCH-QL (Structured Watch Query Language), a temporal extension of SQL, the widespread query language based on the relational model. S-WATCH-QL extends the well-known SQL by the addition of: a) temporal data types that allow the storage of information with different levels of granularity; b) historical relations that can store together both instantaneous valid times and intervals; c) some temporal clauses, functions and predicates allowing to define complex temporal queries. PMID:8947722

Psychopathy & Aggression: When Paralimbic Dysfunction Leads to Violence

PubMed Central

Anderson, Nathaniel E.; Kiehl, Kent A.

2015-01-01

Psychopaths can be alarmingly violent, both in the frequency with which they engage in violence and the gratuitous extent of their violent acts. Indeed, one principal utility of the clinical construct of psychopathy is in predicting future violent behavior in criminal offenders. Aggression is a complex construct that intersects psychopathy at many levels. This chapter provides a review of psychopathy as a clinical construct including the most prominent cognitive and neurobiological models which serve to account for its pathophysiology. We then describe how the brain abnormalities implicated in psychopathy may lead to diverse behavioral outcomes, which can include aggression in its many forms. PMID:24306955

Maternal periodontal disease and preeclampsia in Jaipur population

PubMed Central

Jaiman, Girija; Nayak, Prathibha Anand; Sharma, Sanu; Nagpal, Kiran

2018-01-01

Background: Preeclampsia is identified as an important cause for mother and newborn mortality. Inspite of extensive research, the exact etiological relations have not been established. Hence, an attempt has been made in this study to evaluate the relationship between the preeclampsia and maternal periodontal disease. Materials and Methods: The case–control study comprised of thirty pregnant women distributed equally in the case (preeclampsia) and control (healthy) group. Gingival index, plaque index, bleeding on probing, clinical probing depth, and clinical attachment level were measured in both groups. Microbiologic examination for identification of one red complex organism Porphyromonas gingivalis and one orange complex organism Fusobacterium nucleatum were done in plaque and placental blood of cases and controls. The clinical examinations and collection of placental blood were done 24 h before delivery. Results: Periodontal condition in the preeclamptic women was statistically worse compared with the normotensive women. There was no statistically significant association between microorganisms in plaque and placental blood between normotensive control and preeclamptic pregnant women. The preeclamptic women had significantly higher chances of having newborns weighing <2.5 kg than the normotensive women. Conclusion: The preeclamptic women were associated with significantly higher periodontitis and lower fetal birth weight than normotensive women. PMID:29568173

Maternal periodontal disease and preeclampsia in Jaipur population.

PubMed

Jaiman, Girija; Nayak, Prathibha Anand; Sharma, Sanu; Nagpal, Kiran

2018-01-01

Preeclampsia is identified as an important cause for mother and newborn mortality. Inspite of extensive research, the exact etiological relations have not been established. Hence, an attempt has been made in this study to evaluate the relationship between the preeclampsia and maternal periodontal disease. The case-control study comprised of thirty pregnant women distributed equally in the case (preeclampsia) and control (healthy) group. Gingival index, plaque index, bleeding on probing, clinical probing depth, and clinical attachment level were measured in both groups. Microbiologic examination for identification of one red complex organism Porphyromonas gingivalis and one orange complex organism Fusobacterium nucleatum were done in plaque and placental blood of cases and controls. The clinical examinations and collection of placental blood were done 24 h before delivery. Periodontal condition in the preeclamptic women was statistically worse compared with the normotensive women. There was no statistically significant association between microorganisms in plaque and placental blood between normotensive control and preeclamptic pregnant women. The preeclamptic women had significantly higher chances of having newborns weighing <2.5 kg than the normotensive women. The preeclamptic women were associated with significantly higher periodontitis and lower fetal birth weight than normotensive women.

Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder.

PubMed

Thomaes, K; Dorrepaal, E; Draijer, N; de Ruiter, M B; Elzinga, B M; van Balkom, A J; Smit, J H; Veltman, D J

2012-11-01

Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. At baseline, we compared classic and emotional Stroop performance and blood oxygenation level-dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms.

Implementing the CDC’s Colorectal Cancer Screening Demonstration Program: Wisdom From the Field

PubMed Central

Rohan, Elizabeth A.; Boehm, Jennifer E.; DeGroff, Amy; Glover-Kudon, Rebecca; Preissle, Judith

2017-01-01

BACKGROUND Colorectal cancer, as the second leading cause of cancer-related deaths among men and women in the United States, represents an important area for public health intervention. Although colorectal cancer screening can prevent cancer and detect disease early when treatment is most effective, few organized public health screening programs have been implemented and evaluated. From 2005 to 2009, the Centers for Disease Control and Prevention funded 5 sites to participate in the Colorectal Cancer Screening Demonstration Program (CRCSDP), which was designed to reach medically underserved populations. METHODS The authors conducted a longitudinal, multiple case study to analyze program implementation processes. Qualitative methods included interviews with 100 stakeholders, 125 observations, and review of 19 documents. Data were analyzed within and across cases. RESULTS Several themes related to CRCSDP implementation emerged from the cross-case analysis: the complexity of colorectal cancer screening, the need for teamwork and collaboration, integration of the program into existing systems, the ability of programs to use wisdom at the local level, and the influence of social norms. Although these themes were explored independently from 1 another, interaction across themes was evident. CONCLUSIONS Colorectal cancer screening is clinically complex, and its screening methods are not well accepted by the general public; both of these circumstances have implications for program implementation. Using patient navigation, engaging in transdisciplinary teamwork, assimilating new programs into existing clinical settings, and deferring to local-level wisdom together helped to address complexity and enhance program implementation. In addition, public health efforts must confront negative social norms around colorectal cancer screening. PMID:23868482

Occurrence of socransky red complex in pregnant women with and without periodontal disease.

PubMed

Lima, Daniela Pereira; Moimaz, Suzely Adas Saliba; Garbin, Cléa Adas Saliba; Sumida, Dóris Hissako; Jardim, Elerson Gaetti; Okamoto, Ana Cláudia

2015-01-01

To verify the presence of Socransky Red Complex (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) and P. intermedia using polymerase chain reaction (PCR) in periodontally healthy pregnant women and pregnant women with periodontal disease, as well as its relation to arterial blood pressure and capillary glycaemia. This case control study included 86 pregnant women, including 50 pregnant women with healthy periodontium, 27 with gingivitis and 9 with periodontitis. Arterial blood pressure and glycaemia were evaluated and recorded. Clinical specimens from the gingival crevice or periodontal pockets were gathered with sterile absorbent paper cones. DNA extraction was accomplished using the Easy-DNA Kit test and the presence of bacteria was detected by PCR with primers and specific probes for each microorganism. The arterial pressure of all pregnant women was found to be within normal levels and 51% presented with hyperglycaemia, these two variables were not associated with periodontal conditions and/or presence of microorganisms. Socransky Red Complex was not present in pregnant women with healthy periodontium; however, it was present in pregnant women with gingivitis (3.7%) and in a higher percentage of pregnant women with periodontitis (33.3%). Socransky Red Complex was found only in cases of periodontal diseases and is not related to blood pressure and/or high levels of blood glucose.

Retinal dystrophies, genomic applications in diagnosis and prospects for therapy

PubMed Central

Nash, Benjamin M.; Wright, Dale C.; Grigg, John R.; Bennetts, Bruce

2015-01-01

Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. This review aims to demonstrate the high degree of genetic complexity in both the causative disease genes and their associated phenotypes, highlighting the more common clinical manifestation of retinitis pigmentosa (RP). The review also provides insight to recent advances in genomic molecular diagnosis and gene and cell-based therapies for the RDs. PMID:26835369

Bone morphogenetic proteins in musculoskeletal medicine.

PubMed

Giannoudis, Peter V; Einhorn, Thomas A

2009-12-01

Ongoing research at the molecular level has expanded our understanding of the physiological processes that regulate the complex phenomena of fracture healing and bone regeneration. A number of key molecules have been identified and shown to facilitate the progression of healing from one stage to another, leading to an uneventful outcome. Among these candidate molecules, bone morphogenetic proteins (BMPs) possess potent osteoinductive properties. They interact with osteoprogenitor cells, regulating both mitogenesis and differentiation potential. Since the discovery of BMPs, a number of experimental and clinical trials have supported their safety and efficacy of their use in therapy. Nonetheless, at times their efficacy falls short of expectations. Several factors have been identified as contributing to this result. It is anticipated that, as our knowledge expands and we understand better the complex pathways and cascades of molecular events attributable to BMPs, the application of these molecules in the clinical setting will continue to increase and to show more favourable outcomes. Copyright 2009 Elsevier Ltd. All rights reserved.

Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis.

PubMed

Ellsworth, Darrell L; Blackburn, Heather L; Shriver, Craig D; Rabizadeh, Shahrooz; Soon-Shiong, Patrick; Ellsworth, Rachel E

2017-12-01

Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful. In this review, we: (1) highlight current methodologies and recent technological advances for isolating single cells, single-cell whole-genome and whole-transcriptome amplification using minute amounts of nucleic acids, and SCS, (2) summarize research investigating molecular heterogeneity at the genomic and transcriptomic levels and how this heterogeneity affects clonal evolution and metastasis, and (3) discuss the promise for integrating SCS in the clinical care arena for improved patient care.

Aligning Event Logs to Task-Time Matrix Clinical Pathways in BPMN for Variance Analysis.

PubMed

Yan, Hui; Van Gorp, Pieter; Kaymak, Uzay; Lu, Xudong; Ji, Lei; Chiau, Choo Chiap; Korsten, Hendrikus H M; Duan, Huilong

2018-03-01

Clinical pathways (CPs) are popular healthcare management tools to standardize care and ensure quality. Analyzing CP compliance levels and variances is known to be useful for training and CP redesign purposes. Flexible semantics of the business process model and notation (BPMN) language has been shown to be useful for the modeling and analysis of complex protocols. However, in practical cases one may want to exploit that CPs often have the form of task-time matrices. This paper presents a new method parsing complex BPMN models and aligning traces to the models heuristically. A case study on variance analysis is undertaken, where a CP from the practice and two large sets of patients data from an electronic medical record (EMR) database are used. The results demonstrate that automated variance analysis between BPMN task-time models and real-life EMR data are feasible, whereas that was not the case for the existing analysis techniques. We also provide meaningful insights for further improvement.

Shared decision making and the promise of a respectful and equitable healthcare system in Peru.

PubMed

Málaga, Germán; Romero, Zoila O; Málaga, Ariana S; Cuba-Fuentes, Sofia

2017-06-01

Peru has achieved sustained development in the last two decades. However, despite this achievement, it has not been matched with improvements in the quality of education and health; investment in both sectors is among the lowest in the region. This situation perpetuates huge gaps in infrastructure and also conditions a poor literacy level of the population specifically in health. Currently, there is a fragmented model of patient care, in which the systems are exclusive of each other. They do not cooperate or communicate with each other; and if there is no vertical communication within the system, preventing referral of patients directly from the basic level to the complex level of care when needed. In addition, there has been no progress in the development of an empathetic, respectful or person-centered clinical practice; instead, economic, social and educational differences perpetuate a paternalistic clinical practice. The task of orienting medical training towards the development of humanism is pending. The patient is the center of the medical act and the main objective of doctors' actions. A humanistic care approach will not only empower the person in the clinical encounter - to participate and make decisions related to his/her health care - but it will allow us to move towards an empathetic, caring, respectful and kind model of clinical practice. Copyright © 2017. Published by Elsevier GmbH.

[Application of nootropic agents in complex treatment of patients with concussion of the brain].

PubMed

Tkachev, A V

2007-01-01

65 patients with a mild craniocereberal trauma have been observed. Medical examination included among general clinical methods the following methods: KT (MRT) of the brain, oculist examination including the observation of eye fundus. For objectification of a patient' complaints the authors used orientation and Galvestona's amnesia tests, feeling scale (psychological test), the table to determine the level of memory. Tests have been carried out on the first, tenth and thirty day of the treatment. Patients of the first group received in a complex treatment -pramistar, patients of the second group - piracetam. Patients of both groups noted considerable improvement during a complex treatment (disappearance of headache, dizziness and nausea) and at the same time patients receiving pramistar had better restoration of orientation and feeling. Pramistar was also more effective in patients with amnesia.

Accelerated production of antigen-specific T-cells for pre-clinical and clinical applications using Gas-permeable Rapid Expansion cultureware (G-Rex)

PubMed Central

Vera, Juan F.; Brenner, Lara J.; Gerdemann, Ulrike; Ngo, Minhtran C.; Sili, Uluhan; Liu, Hao; Wilson, John; Dotti, Gianpietro; Heslop, Helen E.; Leen, Ann M.; Rooney, Cliona M.

2009-01-01

The clinical manufacture of antigen-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy is limited by the complexity and time required to produce large numbers with the desired function and specificity. The culture conditions required are rigorous, and in some cases only achieved in 2cm2 wells in which cell growth is limited by gas exchange, nutrients and waste accumulation. Bioreactors developed to overcome these issues tend to be complex, expensive and not always conducive to CTL growth. We observed that antigen-specific CTL undergo seven to ten divisions post-stimulation. However the expected CTL numbers were achieved only in the first week of culture. By recreating the culture conditions present during this first week - low frequency of antigen-specific T-cells and high frequency of feeder cells - we were able to increase CTL expansion to expected levels which could be sustained for several weeks without affecting phenotype or function. However, the number of 24-well plates needed was excessive and cultures required frequent media changes, increasing complexity and manufacturing costs. Therefore, we evaluated novel gas-permeable culture devices (G-Rex) with a silicone membrane at the base allowing gas exchange to occur uninhibited by depth of medium above. This system effectively supports the expansion of CTL and actually increases output by up to 20-fold while decreasing required technician time. Importantly, this amplified cell expansion is not due to more cell divisions but to reduced cell death. This bioprocess optimization increased T-cell output while decreasing the complexity and cost of CTL manufacture, making cell therapy more accessible. PMID:20445351

DIAGNOSTIC ACCURACY OF PHYSICAL EXAMINATION TESTS OF THE ANKLE/FOOT COMPLEX: A SYSTEMATIC REVIEW

PubMed Central

Schwieterman, Braun; Haas, Deniele; Columber, Kirby; Knupp, Darren

2013-01-01

Background: Orthopedic special tests of the ankle/foot complex are routinely used during the physical examination process in order to help diagnose ankle/lower leg pathologies. Purpose: The purpose of this systematic review was to investigate the diagnostic accuracy of ankle/lower leg special tests. Methods: A search of the current literature was conducted using PubMed, CINAHL, SPORTDiscus, ProQuest Nursing and Allied Health Sources, Scopus, and Cochrane Library. Studies were eligible if they included the following: 1) a diagnostic clinical test of musculoskeletal pathology in the ankle/foot complex, 2) description of the clinical test or tests, 3) a report of the diagnostic accuracy of the clinical test (e.g. sensitivity and specificity), and 4) an acceptable reference standard for comparison. The quality of included studies was determined by two independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results: Nine diagnostic accuracy studies met the inclusion criteria for this systematic review; analyzing a total of 16 special tests of the ankle/foot complex. After assessment using the QUADAS-2, only one study had low risk of bias and low concerns regarding applicability. Conclusion: Most ankle/lower leg orthopedic special tests are confirmatory in nature and are best utilized at the end of the physical examination. Most of the studies included in this systematic review demonstrate notable biases, which suggest that results and recommendations in this review should be taken as a guide rather than an outright standard. There is need for future research with more stringent study design criteria so that more accurate diagnostic power of ankle/lower leg special tests can be determined. Level of Evidence: 3a PMID:24175128

Leadership role of Consultant Nurses working with Older People: a co-operative inquiry.

PubMed

Manley, Kim; Webster, Jonathan; Hale, Nick; Hayes, Nicky; Minardi, Henry

2008-03-01

The aim of the co-operative enquiry undertaken was to explore how the leadership component of the Consultant Nurse for Older People role was reflected in day-to-day working. Leadership is one of the four key elements of the Consultant Nurse role and is the key mechanism for achieving and embedding transformation in practice. However, within the role of the Consultant Nurse this area has not been explored in detail. A 6-month co-operative inquiry approach was used to develop insights into leadership strategies of Consultant Nurses for Older People and involved the five authors of the paper, four Consultant Nurses in Older People nursing and the lead author who was also an experienced Consultant Nurse and practice-based researcher from a different nursing specialism. Through the analysis of the stories shared by the co-authors/participants, two key themes emerged relating to complexity and pathway. These themes provided a major focus for the Consultant Nurses in their leadership role. The outcome of the study is a framework that describes the triggers and enabling factors that precede the use of leadership strategies at the clinical and organizational level and associated outcomes. In defining how leadership is reflected by Consultant Nurses for Older People, a complex picture emerges that is multifaceted and multidimensional. Consultant Nurses need support to make visible the valuable contribution they make to enabling healthcare teams, organizations and work places. Consultant Nurses for Older People are key in ensuring the quality agenda within their organizations as they are well placed to provide leadership at both a strategic and clinical level, while providing influence to operational development. Within the context of the literature this area is under investigated. Understanding how leadership is reflected in the role of Consultant Nurses is complex as Consultant Nurses work across traditional interfaces and between different levels within organizations. Consultant Nurses have been 'challenged' to identify the 'difference' they are making; to do this it is important to understand how leadership (as one element) is reflected in a highly complex, multidimensional role and the links between leadership and enabling, quality person-centred ways of working with Older People within rapidly changing, pressurized healthcare settings.

Dealing with Diversity in Computational Cancer Modeling

PubMed Central

Johnson, David; McKeever, Steve; Stamatakos, Georgios; Dionysiou, Dimitra; Graf, Norbert; Sakkalis, Vangelis; Marias, Konstantinos; Wang, Zhihui; Deisboeck, Thomas S.

2013-01-01

This paper discusses the need for interconnecting computational cancer models from different sources and scales within clinically relevant scenarios to increase the accuracy of the models and speed up their clinical adaptation, validation, and eventual translation. We briefly review current interoperability efforts drawing upon our experiences with the development of in silico models for predictive oncology within a number of European Commission Virtual Physiological Human initiative projects on cancer. A clinically relevant scenario, addressing brain tumor modeling that illustrates the need for coupling models from different sources and levels of complexity, is described. General approaches to enabling interoperability using XML-based markup languages for biological modeling are reviewed, concluding with a discussion on efforts towards developing cancer-specific XML markup to couple multiple component models for predictive in silico oncology. PMID:23700360

Leverage hadoop framework for large scale clinical informatics applications.

PubMed

Dong, Xiao; Bahroos, Neil; Sadhu, Eugene; Jackson, Tommie; Chukhman, Morris; Johnson, Robert; Boyd, Andrew; Hynes, Denise

2013-01-01

In this manuscript, we present our experiences using the Apache Hadoop framework for high data volume and computationally intensive applications, and discuss some best practice guidelines in a clinical informatics setting. There are three main aspects in our approach: (a) process and integrate diverse, heterogeneous data sources using standard Hadoop programming tools and customized MapReduce programs; (b) after fine-grained aggregate results are obtained, perform data analysis using the Mahout data mining library; (c) leverage the column oriented features in HBase for patient centric modeling and complex temporal reasoning. This framework provides a scalable solution to meet the rapidly increasing, imperative "Big Data" needs of clinical and translational research. The intrinsic advantage of fault tolerance, high availability and scalability of Hadoop platform makes these applications readily deployable at the enterprise level cluster environment.

The complex interplay between clinical and person-centered diabetes outcomes in the two genders.

PubMed

Rossi, Maria Chiara; Lucisano, Giuseppe; Pintaudi, Basilio; Bulotta, Angela; Gentile, Sandro; Scardapane, Marco; Skovlund, Soren Eik; Vespasiani, Giacomo; Nicolucci, Antonio

2017-02-21

New approaches to cope with clinical and psychosocial aspects of type 2 diabetes (T2DM) are needed; gender influences the complex interplay between clinical and non-clinical factors. We used data from the BENCH-D study to assess gender-differences in terms of clinical and person-centered measures in T2DM. Clinical quality of care indicators relative to control of HbA1c, lipid profile, blood pressure, and BMI were derived from electronic medical records. Ten self-administered validated questionnaires (SF-12 Health Survey; WHO-5 well-being index; Problem Areas in Diabetes (PAID) 5, Health Care Climate Questionnaire, Patients Assessment of Chronic Illness Care, Diabetes Empowerment Scale, Diabetes Self-care Activities, Global Satisfaction for Diabetes Treatment, Barriers to Taking Medications, Perceived Social Support) were adopted as person-centered outcomes indicators. Overall, 26 diabetes clinics enrolled 2,335 people (men: 59.7%; women: 40.3%). Lower percentages of women reached HbA1c levels < =7.0% (23.2% vs. 27.8%; p = 0.03), LDL-cholesterol < 100 mg/dl (48.3 vs. 57.8%; p = 0.0005), and BMI <27 Kg/m2 (27.2 vs. 31.6%; p = 0.04) than men. Women had statistically significant poorer scores for physical functioning, psychological well-being, self-care activities dedicated to physical activities, empowerment, diabetes-related distress, satisfaction with treatment, barriers to medication taking, satisfaction with access to chronic care and healthcare communication, and perceived social support than men; 24.8% of women and 8.8% of men had WHO-5 < =28 (likely depression) (p < 0.0001); 67.7% of women and 55.1% of men had PAID-5 > 40 (high levels of diabetes-related distress) (p < 0.0001). At multivariate analysis, factors associated with an increased likelihood of having elevated HbA1c levels (≥8.0%) were different in men and women, e.g. having PAID-5 levels >40 was associated with a higher likelihood of HbA1c ≥8.0% in women (OR = 1.15; 95%CI 1.05-1.25) but not in men (OR = 1.00; 95%CI 0.93-1.08). In T2DM, women show poorer clinical and person-centered outcomes indicators than men. Diabetes-related distress plays a role as a correlate of metabolic control in women but not in men. The study provides new information about the interplay between clinical and person-centered indicators in men and women which may guide further improvements in diabetes education and support programs.

Service quality and clinical outcomes: an example from mental health rehabilitation services in England.

PubMed

Killaspy, Helen; Marston, Louise; Omar, Rumana Z; Green, Nicholas; Harrison, Isobel; Lean, Melanie; Holloway, Frank; Craig, Tom; Leavey, Gerard; King, Michael

2013-01-01

Current health policy assumes better quality services lead to better outcomes. To investigate the relationship between quality of mental health rehabilitation services in England, local deprivation, service user characteristics and clinical outcomes. Standardised tools were used to assess the quality of mental health rehabilitation units and service users' autonomy, quality of life, experiences of care and ratings of the therapeutic milieu. Multiple level modelling investigated relationships between service quality, service user characteristics and outcomes. A total of 52/60 (87%) National Health Service trusts participated, comprising 133 units and 739 service users. All aspects of service quality were positively associated with service users' autonomy, experiences of care and therapeutic milieu, but there was no association with quality of life. Quality of care is linked to better clinical outcomes in people with complex and longer-term mental health problems. Thus, investing in quality is likely to show real clinical gains.

An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre.

PubMed

Huda, S; Wong, S H; Pettingill, P; O'Connell, D; Vincent, A; Steiger, M

2015-02-01

Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan's syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres <400 pM were seen with PNH (n = 15/22; 68 %) but also a heterogeneous range of central and/or peripheral nervous system disorders. Electromyography was supportive of PNH in 65 % of cases and symptomatic treatment was beneficial in 46 % of patients. Irrespective of titre, the rate of malignancy in patients with VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97-44.0 p<0.0001). Clinical phenotyping and antibody titres >400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.

[Patient-related complexity in nursing care - Collective case studies in the acute care hospital].

PubMed

Gurtner, Caroline; Spirig, Rebecca; Staudacher, Diana; Huber, Evelyn

2018-06-04

Patient-related complexity in nursing care - Collective case studies in the acute care hospital Abstract. Patient-related complexity of nursing is defined by the three characteristics "instability", "uncertainty", and "variability". Complexity increased in the past years, due to reduced hospital length of stay and a growing number of patients with chronic and multiple diseases. We investigated the phenomenon of patient-related complexity from the point of view of nurses and clinical nurse specialists in an acute care hospital. In the context of a collective case study design, nurses and clinical nurse specialists assessed the complexity of nursing situations with a questionnaire. Subsequently, we interviewed nurses and clinical nurse specialists about their evaluation of patient-related complexity. In a within-case-analysis we summarized data inductively to create case narratives. By means of a cross-case-analysis we compared the cases with regard to deductively derived characteristics. The four cases exemplarily showed that the degree of complexity depends on the controllability and predictability of clinical problems. Additionally, complexity increases or decreases, according to patients' individual resources. Complex patient situations demand professional expertise, experience, communicative competencies and the ability for reflection. Beginner nurses would benefit from support and advice by experienced nurses to develop these skills.

Living longer living happier: My journey from clinical neurology to complexities of brain

PubMed Central

Panagariya, Ashok

2011-01-01

The present article is a treatise on the illuminating voyage of a Neurophysician along the fascinating horizons and frontiers of neurosciences. During the career as a clinical neurologist, some very interesting and intriguing cases and issues were dealt with and documented scientifically. The working of the brain and its operational architectonics came up for critical analysis, opening up new vistas in the appreciation and management of various neurological disorders. Issues regarding the working of the mind and the guidelines for health and happiness became apparent, and some very interesting generalizations with far-reaching consequences on the general well-being and health have been formulated and put forward for a healthy and happy future for mankind. A paradigm shift is warranted for a closer and better appreciation of neural dynamics at all levels of the brain, namely microscopic, mesoscopic and macroscopic levels! PMID:22346008

Safety study and characterization of E1A-liposome complex gene-delivery protocol in an ovarian cancer model.

PubMed

Xing, X; Zhang, S; Chang, J Y; Tucker, S D; Chen, H; Huang, L; Hung, M C

1998-11-01

A phase I clinical trial of E1A-liposome complex is currently ongoing in patients with HER-2/neu-overexpressing breast or ovarian cancers. To optimize the E1A-liposome complex for a further stage of clinical trial, several aspects of the current protocol have been examined in an animal model. In the orthotopic ovarian cancer model, different doses of lipid in the the E1A-liposome complex, which is currently used in clinical trials, were tested for the in vivo gene-transfer efficacy and tumor-suppression function. A lowered lipid dose--1/13 of the previous amount--produced gene expression level and E1A tumor-suppression efficacy similar to that of the original protocol. Mini-E1A, an E1A construct without its immortalization domain and yet capable of repressing HER-2/neu, was proved to be as potent as E1A in suppressing tumor development in vivo. These changes in the E1A-liposome complex will significantly reduce any potential adverse effects caused by lipid vector and E1A DNA. To examine further whether residual E1A DNA may still exist in normal organs after the E1A-liposome treatment, PCR was used to detect E1A DNA in mice that survived for 1 1/2 years after the last treatment. E1A DNA was detected only in the lungs and kidneys, but not in livers, hearts, spleens, brains, uterus or the ovaries. Furthermore, resistance of the E1A DNA extracted from tissues to the digestion of Dpnl restriction enzyme, which can cleave the methylated E1A plasmid DNA generated by methylation-competent bacteria, suggested integration of E1A DNA into the chromosome of the lungs and kidneys. Experimental results presented here provide important information for safety concerns and for the design of future phase II and phase III trials.

[Clinical-diagnostic estimation of carbohydrates metabolism in obturation jaundice].

PubMed

Nychytaĭlo, M Iu; Malyk, S V

2004-07-01

Complex examination of 175 patients with obturation jaundice was conducted, peculiar attention was spared to the carbohydrates metabolism changes, characterizing hepatic state. It was established, that in obturation jaundice in the liver there are occurring inflammatory changes and disturbances of all kinds of metabolism, including that of carbohydrates, severity of which depends on duration of jaundice, the concurrent diseases presence, they shows lowering of the glucose and glycogen level in the blood, as well as the hepatic glycogen content, that's why they may be applied as a complex of prognostic criterions for the disease course. An early conduction of operative treatment, elimination of the biliary ducts impassability promote the rehabilitation period shortening and the hepatic functional activity normalization.

Sub-inhibitory concentrations of oxacillin modify the expression of agr locus in Staphylococcus aureus clinical strains belonging to different clonal complexes.

PubMed

Viedma, Esther; Pérez-Montarelo, Dafne; Villa, Jennifer; Muñoz-Gallego, Irene; Larrosa, Nieves; Fernández-Hidalgo, Nuria; Gavaldà, Joan; Almirante, Benito; Chaves, Fernando

2018-04-16

The ability of Staphylococcus aureus to invade tissues and cause an infectious disease is the result of a multi-factorial process supported by the huge number of virulence factors inherent to this microorganism tightly regulated by the accessory gene regulator (agr). During antimicrobial therapy bacteria may be exposed to sub-inhibitory concentrations (subMICs) of antibiotics that may trigger transcriptional changes that may have an impact on the pathogenesis of infection. The objective of this study was to investigate the effect of oxacillin sub-MICs on agr system expression as the key component in the regulation of virulence in methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA) strains. Furthermore, we studied the genetic basis of the agr locus and their potential association with the expression levels. We have examined the expression of RNAIII and agrA mRNA as biomarkers for agr expression in the presence and absence of oxacillin subMICs in 10 MSSA and 4 MRSA clinical strains belonging to 5 clonal complexes (CC45-agrI, CC8-agrI, CC5-agrII, CC15-agrII and CC30-agrIII) causing endovascular complications. The DNA sequences of agr locus were obtained by whole genome sequencing. Our results revealed that exposure to subMICs of oxacillin had an impact on agr locus expression modifying the relative levels of expression with increases in 11 strains and with decreases in 3 strains. Thereby, the exposure to subMICs of oxacillin resulted in higher levels of expression of agr in CC15 and CC45 and lower levels in CC30. We also observed the presence of mutations in agrC and agrA in 13/14 strains with similar mutation profiles among strains within individual CCs except for strains of CC5. Although, agr expression levels differed among strains within CCs, the presence of these mutations was associated with differences in agr expression levels in most cases. Changes in agr expression induced by exposure to oxacillin subMICs should be considered because they could lead to changes in the virulence modulation and have an adverse effect on the course of infection, especially in certain clonal complexes.

Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy.

PubMed

Sleeper, Meg M; Rosato, Bradley P; Bansal, Seema; Avadhani, Narayan G

2012-11-01

To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty

PubMed Central

Schiavazzi, Daniele E.; Baretta, Alessia; Pennati, Giancarlo; Hsia, Tain-Yen; Marsden, Alison L.

2017-01-01

Summary Computational models of cardiovascular physiology can inform clinical decision-making, providing a physically consistent framework to assess vascular pressures and flow distributions, and aiding in treatment planning. In particular, lumped parameter network (LPN) models that make an analogy to electrical circuits offer a fast and surprisingly realistic method to reproduce the circulatory physiology. The complexity of LPN models can vary significantly to account, for example, for cardiac and valve function, respiration, autoregulation, and time-dependent hemodynamics. More complex models provide insight into detailed physiological mechanisms, but their utility is maximized if one can quickly identify patient specific parameters. The clinical utility of LPN models with many parameters will be greatly enhanced by automated parameter identification, particularly if parameter tuning can match non-invasively obtained clinical data. We present a framework for automated tuning of 0D lumped model parameters to match clinical data. We demonstrate the utility of this framework through application to single ventricle pediatric patients with Norwood physiology. Through a combination of local identifiability, Bayesian estimation and maximum a posteriori simplex optimization, we show the ability to automatically determine physiologically consistent point estimates of the parameters and to quantify uncertainty induced by errors and assumptions in the collected clinical data. We show that multi-level estimation, that is, updating the parameter prior information through sub-model analysis, can lead to a significant reduction in the parameter marginal posterior variance. We first consider virtual patient conditions, with clinical targets generated through model solutions, and second application to a cohort of four single-ventricle patients with Norwood physiology. PMID:27155892

Registered nurses' clinical reasoning in home healthcare clinical practice: A think-aloud study with protocol analysis.

PubMed

Johnsen, Hege Mari; Slettebø, Åshild; Fossum, Mariann

2016-05-01

The home healthcare context can be unpredictable and complex, and requires registered nurses with a high level of clinical reasoning skills and professional autonomy. Thus, additional knowledge about registered nurses' clinical reasoning performance during patient home care is required. The aim of this study is to describe the cognitive processes and thinking strategies used by recently graduated registered nurses while caring for patients in home healthcare clinical practice. An exploratory qualitative think-aloud design with protocol analysis was used. Home healthcare visits to patients with stroke, diabetes, and chronic obstructive pulmonary disease in seven healthcare districts in southern Norway. A purposeful sample of eight registered nurses with one year of experience. Each nurse was interviewed using the concurrent think-aloud technique in three different patient home healthcare clinical practice visits. A total of 24 home healthcare visits occurred. Follow-up interviews were conducted with each participant. The think-aloud sessions were transcribed and analysed using three-step protocol analysis. Recently graduated registered nurses focused on both general nursing concepts and concepts specific to the domains required and tasks provided in home healthcare services as well as for different patient groups. Additionally, participants used several assertion types, cognitive processes, and thinking strategies. Our results showed that recently graduated registered nurses used both simple and complex cognitive processes involving both inductive and deductive reasoning. However, their reasoning was more reactive than proactive. The results may contribute to nursing practice in terms of developing effective nursing education programmes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.

PubMed

Low, Siew-Kee; Chung, Suyoun; Takahashi, Atsushi; Zembutsu, Hitoshi; Mushiroda, Taisei; Kubo, Michiaki; Nakamura, Yusuke

2013-08-01

Chemotherapeutic agents are notoriously known to have a narrow therapeutic range that often results in life-threatening toxicity. Hence, it is clinically important to identify the patients who are at high risk for severe toxicity to certain chemotherapy through a pharmacogenomics approach. In this study, we carried out multiple genome-wide association studies (GWAS) of 13 122 cancer patients who received different chemotherapy regimens, including cyclophosphamide- and platinum-based (cisplatin and carboplatin), anthracycline-based (doxorubicin and epirubicin), and antimetabolite-based (5-fluorouracil and gemcitabine) treatment, antimicrotubule agents (paclitaxel and docetaxel), and topoisomerase inhibitors (camptothecin and etoposide), as well as combination therapy with paclitaxel and carboplatin, to identify genetic variants that are associated with the risk of severe neutropenia/leucopenia in the Japanese population. In addition, we used a weighted genetic risk scoring system to evaluate the cumulative effects of the suggestive genetic variants identified from GWAS in order to predict the risk levels of individuals who carry multiple risk alleles. Although we failed to identify genetic variants that surpassed the genome-wide significance level (P < 5.0 × 10(-8) ) through GWAS, probably due to insufficient statistical power and complex clinical features, we were able to shortlist some of the suggestive associated loci. The current study is at the relatively preliminary stage, but does highlight the complexity and problematic issues associated with retrospective pharmacogenomics studies. However, we hope that verification of these genetic variants through local and international collaborations could improve the clinical outcome for cancer patients. © 2013 Japanese Cancer Association.

Understanding complex clinical reasoning in infectious diseases for improving clinical decision support design.

PubMed

Islam, Roosan; Weir, Charlene R; Jones, Makoto; Del Fiol, Guilherme; Samore, Matthew H

2015-11-30

Clinical experts' cognitive mechanisms for managing complexity have implications for the design of future innovative healthcare systems. The purpose of the study is to examine the constituents of decision complexity and explore the cognitive strategies clinicians use to control and adapt to their information environment. We used Cognitive Task Analysis (CTA) methods to interview 10 Infectious Disease (ID) experts at the University of Utah and Salt Lake City Veterans Administration Medical Center. Participants were asked to recall a complex, critical and vivid antibiotic-prescribing incident using the Critical Decision Method (CDM), a type of Cognitive Task Analysis (CTA). Using the four iterations of the Critical Decision Method, questions were posed to fully explore the incident, focusing in depth on the clinical components underlying the complexity. Probes were included to assess cognitive and decision strategies used by participants. The following three themes emerged as the constituents of decision complexity experienced by the Infectious Diseases experts: 1) the overall clinical picture does not match the pattern, 2) a lack of comprehension of the situation and 3) dealing with social and emotional pressures such as fear and anxiety. All these factors contribute to decision complexity. These factors almost always occurred together, creating unexpected events and uncertainty in clinical reasoning. Five themes emerged in the analyses of how experts deal with the complexity. Expert clinicians frequently used 1) watchful waiting instead of over- prescribing antibiotics, engaged in 2) theory of mind to project and simulate other practitioners' perspectives, reduced very complex cases into simple 3) heuristics, employed 4) anticipatory thinking to plan and re-plan events and consulted with peers to share knowledge, solicit opinions and 5) seek help on patient cases. The cognitive strategies to deal with decision complexity found in this study have important implications for design future decision support systems for the management of complex patients.

Circulating Immune Complexes in Lyme Arthritis

PubMed Central

Hardin, John A.; Walker, Lesley C.; Steere, Allen C.; Trumble, Thomas C.; Tung, Kenneth S. K.; Williams, Ralph C.; Ruddy, Shaun; Malawista, Stephen E.

1979-01-01

We have found immunoglobulin (Ig) G-containing material consistent with immune complexes in the sera of patients with Lyme arthritis. It was detected in 29 of 55 sera (55%) from 31 patients by at least one of three assays: 125I-C1q binding, C1q solid phase, or Raji cell. The presence of reactive material correlated with clinical aspects of disease activity; it was found early in the illness, was most prominent in sera from the sickest patients, was infrequent during remissions, and often fluctuated in parallel with changes in clinical status. The results in the two C1q assays showed a strong positive correlation (P<0.001). They were each elevated in 45% of the sera and were usually concordant (85%). In contrast, the Raji cell assay was less frequently positive and often discordant with the C1q assays. In sucrose density gradients, putative circulating immune complexes sedimented near 19S; they, too, were detected best by the two assays based on C1q binding. An additional 7S component was found in some sera by the 125I-C1q binding assay. Serum complement was often above the range of normal in patients with mild disease and normal in patients with severe disease but did not correlate significantly with levels of circulating immune complexes. IgM and IgG rheumatoid factors were not detectable. These findings support a role for immune complexes in the pathogenesis of Lyme arthritis. Their measurement, by either the 125I-C1q binding assay or by the C1q solid phase assay, often provides a sensitive index of disease activity. Moreover, the complexes are likely sources of disease-related antigens for further study of this new disorder. PMID:429566

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

PubMed Central

Hurley, James C.

2013-01-01

Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged. PMID:24351718

Evaluation of Genotypic and Phenotypic Protease Virulence Tests for Dichelobacter nodosus Infection in Sheep

PubMed Central

McPherson, Andrew S.; Dhungyel, Om P.

2017-01-01

ABSTRACT Dichelobacter nodosus is a fastidious, strictly anaerobic bacterium, an obligate parasite of the ruminant hoof, and the essential causative agent of virulent ovine footrot. The clinical disease results from a complex interplay between the pathogen, the environment, and the host. Sheep flocks diagnosed with virulent but not benign footrot in Australia may be quarantined and required to undergo a compulsory eradication program, with costs met by the farmer. Virulence of D. nodosus at least partially depends on the elaboration of a protease encoded by aprV2 and manifests as elastase activity. Laboratory virulence tests are used to assist diagnosis because clinical differentiation of virulent and benign footrot can be challenging during the early stages of disease or when the disease is not fully expressed due to unfavorable pasture conditions. Using samples collected from foot lesions from 960 sheep from 40 flocks in four different geographic regions, we evaluated the analytical characteristics of qPCR tests for the protease gene alleles aprV2 and aprB2, and compared these with results from phenotypic protease (elastase and gelatin gel) tests. There was a low level of agreement between clinical diagnosis and quantitative PCR (qPCR) test outcomes at both the flock and sample levels and poor agreement between qPCR test outcomes and the results of phenotypic virulence tests. The diagnostic specificity of the qPCR test was low at both the flock and individual swab levels (31.3% and 18.8%, respectively). By contrast, agreement between the elastase test and clinical diagnosis was high at both the flock level (diagnostic sensitivity [DSe], 100%; diagnostic specificity [DSp], 78.6%) and the isolate level (DSe, 69.5%; DSp, 80.5%). PMID:28202796

Evaluation of Genotypic and Phenotypic Protease Virulence Tests for Dichelobacter nodosus Infection in Sheep.

PubMed

McPherson, Andrew S; Dhungyel, Om P; Whittington, Richard J

2017-05-01

Dichelobacter nodosus is a fastidious, strictly anaerobic bacterium, an obligate parasite of the ruminant hoof, and the essential causative agent of virulent ovine footrot. The clinical disease results from a complex interplay between the pathogen, the environment, and the host. Sheep flocks diagnosed with virulent but not benign footrot in Australia may be quarantined and required to undergo a compulsory eradication program, with costs met by the farmer. Virulence of D. nodosus at least partially depends on the elaboration of a protease encoded by aprV2 and manifests as elastase activity. Laboratory virulence tests are used to assist diagnosis because clinical differentiation of virulent and benign footrot can be challenging during the early stages of disease or when the disease is not fully expressed due to unfavorable pasture conditions. Using samples collected from foot lesions from 960 sheep from 40 flocks in four different geographic regions, we evaluated the analytical characteristics of qPCR tests for the protease gene alleles aprV2 and aprB2 , and compared these with results from phenotypic protease (elastase and gelatin gel) tests. There was a low level of agreement between clinical diagnosis and quantitative PCR (qPCR) test outcomes at both the flock and sample levels and poor agreement between qPCR test outcomes and the results of phenotypic virulence tests. The diagnostic specificity of the qPCR test was low at both the flock and individual swab levels (31.3% and 18.8%, respectively). By contrast, agreement between the elastase test and clinical diagnosis was high at both the flock level (diagnostic sensitivity [DSe], 100%; diagnostic specificity [DSp], 78.6%) and the isolate level (DSe, 69.5%; DSp, 80.5%). Copyright © 2017 McPherson et al.

Clinical informatics in undergraduate teaching of health informatics.

PubMed

Pantazi, Stefan V; Pantazi, Felicia; Daly, Karen

2011-01-01

We are reporting on a recent experience with Health Informatics (HI) teaching at undergraduate degree level to an audience of HI and Pharmacy students. The important insight is that effective teaching of clinical informatics must involve highly interactive, applied components in addition to the traditional theoretical material. This is in agreement with general literature underlining the importance of simulations and role playing in teaching and is well supported by our student evaluation results. However, the viability and sustainability of such approaches to teaching hinges on significant course preparation efforts. These efforts consist of time-consuming investigations of informatics technologies, applications and systems followed by the implementation of workable solutions to a wide range of technical problems. In effect, this approach to course development is an involved process that relies on a special form of applied research whose technical complexity could explain the dearth of published reports on similar approaches in HI education. Despite its difficulties, we argue that this approach can be used to set a baseline for clinical informatics training at undergraduate level and that its implications for HI education in Canada are of importance.

2015 Clinical trials update in sickle cell anemia

PubMed Central

Archer, Natasha; Galacteros, Frédéric; Brugnara, Carlo

2017-01-01

Polymerization of HbS and cell sickling are the prime pathophysiological events in sickle cell disease (SCD). Over the last 30 years, a substantial understanding at the molecular level has been acquired on how a single amino acid change in the structure of the beta chain of hemoglobin leads to the explosive growth of the HbS polymer and the associated changes in red cell morphology. O2 tension and intracellular HbS concentration are the primary molecular drivers of this process, and are obvious targets for developing new therapies. However, polymerization and sickling are driving a complex network of associated cellular changes inside and outside of the erythrocyte, which become essential components of the inflammatory vasculopathy and result in a large range of potential acute and chronic organ damages. In these areas, a multitude of new targets for therapeutic developments have emerged, with several ongoing or planned new therapeutic interventions. This review outlines the key points of SCD pathophysiology as they relate to the development of new therapies, both at the pre-clinical and clinical levels. PMID:26178236

Induction of DNA-protein cross-links by platinum compounds.

PubMed

Woźniak, K; Walter, Z

2000-01-01

The differences between cis- and trans-diamminedichloroplatinum II (DDP) in forming DNA-protein cross-links in isolated human lymphocytes were investigated. Both cis- and trans-DDP can induce DNA-protein cross-links. We show that cis-DDP forms complexes between DNA and proteins faster than trans-DDP. This results from an increase in the quantity of DNA and platinum together with an increase in drug concentration. Under the same conditions trans-DDP causes a decrease in DNA-forming complexes with proteins. After a 12 h incubation of lymphocytes we observe a similar level of DNA in DNA-protein cross-links induced by DDP isomers, but more platinum appears in complexes induced by trans-DDP. The results obtained demonstrate that the antitumor drug - cis-DDP and the clinically ineffective trans-DDP induce links between DNA and proteins in a different manner. We suggest that the therapeutic activity of cis-DDP can in part arise from rapidly forming DNA-protein complexes which can destroy the most important cellular processes, such as replication and transcription.

Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome.

PubMed

Gu Urban, Gucci Jijuan; Friedman, Mikaela; Ren, Ping; Törn, Carina; Fex, Malin; Hampe, Christiane S; Lernmark, Åke; Landegren, Ulf; Kamali-Moghaddam, Masood

2015-06-16

Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.

The relationship between the INTERMED patient complexity instrument and Level of Care Utilisation System (LOCUS).

PubMed

Thurber, Steven; Wilson, Ann; Realmuto, George; Specker, Sheila

2018-03-01

To investigate the concurrent and criterion validity of two independently developed measurement instruments, INTERMED and LOCUS, designed to improve the treatment and clinical management of patients with complex symptom manifestations. Participants (N = 66) were selected from hospital records based on the complexity of presenting symptoms, with tripartite diagnoses across biological, psychiatric and addiction domains. Biopsychosocial information from hospital records were submitted to INTERMED and LOCUS grids. In addition, Global Assessment of Functioning (GAF) ratings were gathered for statistical analyses. The product moment correlation between INTERMED and LOCUS was 0.609 (p = .01). Inverse zero-order correlations for INTERMED and LOCUS total score and GAF were obtained. However, only the beta weight for LOCUS and GAF was significant. An exploratory principal components analysis further illuminated areas of convergence between the instruments. INTERMED and LOCUS demonstrated shared variance. INTERMED appeared more sensitive to complex medical conditions and severe physiological reactions, whereas LOCUS findings are more strongly related to psychiatric symptoms. Implications are discussed.

The complexity of nurses' attitudes toward euthanasia: a review of the literature

PubMed Central

Berghs, M; d Dierckx; Gastmans, C

2005-01-01

In this literature review, a picture is given of the complexity of nursing attitudes toward euthanasia. The myriad of data found in empirical literature is mostly framed within a polarised debate and inconclusive about the complex reality behind attitudes toward euthanasia. Yet, a further examination of the content as well as the context of attitudes is more revealing. The arguments for euthanasia have to do with quality of life and respect for autonomy. Arguments against euthanasia have to do with non-maleficence, sanctity of life, and the notion of the slippery slope. When the context of attitudes is examined a number of positive correlates for euthanasia such as age, nursing specialty, and religion appear. In a further analysis of nurses' comments on euthanasia, it is revealed that part of the complexity of nursing attitudes toward euthanasia arises because of the needs of nurses at the levels of clinical practice, communication, emotions, decision making, and ethics. PMID:16076966

Microchip Immunoaffinity Electrophoresis of Antibody-Thymidine Kinase 1 Complex

PubMed Central

Pagaduan, Jayson V.; Ramsden, Madison; O’Neill, Kim; Woolley, Adam T.

2015-01-01

Thymidine kinase-1 (TK1) is an important cancer biomarker whose serum levels are elevated in early cancer development. We developed a microchip electrophoresis immunoaffinity assay to measure recombinant purified TK1 (pTK1) using an antibody that binds to human TK1. We fabricated poly(methyl methacrylate) microfluidic devices to test the feasibility of detecting antibody (Ab)-pTK1 immune complexes as a step towards TK1 analysis in clinical serum samples. We were able to separate immune complexes from unbound antibodies using 0.5X phosphate buffer saline (pH 7.4) containing 0.01% Tween-20, with 1% w/v methylcellulose that acts as a dynamic surface coating and sieving matrix. Separation of the antibody and Ab-pTK1 complex was observed within a 5 mm effective separation length. This method of detecting pTK1 is easy to perform, requires only a 10 μL sample volume, and takes just 1 minute for separation. PMID:25486911

Short Communication: Transplacental Nucleoside Analogue Exposure and Mitochondrial Parameters in HIV-Uninfected Children

PubMed Central

Brogly, Susan B.; DiMauro, Salvatore; Van Dyke, Russell B.; Williams, Paige L.; Naini, Ali; Libutti, Daniel E.; Choi, Julia; Chung, Michelle

2011-01-01

Abstract Transplacental nucleoside analogue exposure can affect infant mitochondrial DNA (mtDNA). We evaluated mitochondria in peripheral blood mononuclear cells of children with and without clinical signs of mitochondrial dysfunction (MD) and antiretroviral (ARV) exposure. We previously identified 20 children with signs of MD (cases) among 1037 HIV-uninfected children born to HIV-infected women. We measured mtDNA copies/cell and oxidative phosphorylation (OXPHOS) NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV) protein levels and enzyme activities, determined mtDNA haplogroups and deletions in 18 of 20 cases with stored samples and in sex- and age-matched HIV-uninfected children, both ARV exposed and unexposed, (1) within 18 months of birth and (2) at the time of presentation of signs of MD. In specimens drawn within 18 months of birth, mtDNA levels were higher and OXPHOS protein levels and enzyme activities lower in cases than controls. In contrast, at the time of MD presentation, cases and ARV-exposed controls had lower mtDNA levels, 214 and 215 copies/cell, respectively, than ARV-unexposed controls, 254 copies/cell. OXPHOS protein levels and enzyme activities were lower in cases than exposed controls, and higher in cases than unexposed controls, except for complex IV activity, which was higher in cases. Haplotype H was less frequent among cases (6%) than controls (31%). No deletions were found. The long-term significance of these small but potentially important alterations should continue to be studied as these children enter adolescence and adulthood. PMID:21142587

[Implications in primary health care of medical genetics and genomic in type 2 diabetes mellitus].

PubMed

Ramirez-Garcia, Sergio Alberto; Cabrera-Pivaral, Carlos E; Huacuja-Ruiz, Luis; Flores-Alvarado, Luis Javier; Pérez-García, Guillermo; González-Rico, José Luis; López-Velázquez, Alma; Topete-González, Luz Rosalba; Rosales-Góme, Roberto Carlos; Candelario-Mejía, Gerardo; Villa-Ruano, Nemesio

2013-01-01

Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

Music therapy with disorders of consciousness: current evidence and emergent evidence-based practice.

PubMed

Magee, Wendy L; O'Kelly, Julian

2015-03-01

Patients with prolonged disorders of consciousness (PDOC) stemming from acquired brain injury present one of the most challenging clinical populations in neurological rehabilitation. Because of the complex clinical presentation of PDOC patients, treatment teams are confronted with many medicolegal, ethical, philosophical, moral, and religious issues in day-to-day care. Accurate diagnosis is of central concern, relying on creative approaches from skilled clinical professionals using combined behavioral and neurophysiological measures. This paper presents the latest evidence for using music as a diagnostic tool with PDOC, including recent developments in music therapy interventions and measurement. We outline standardized clinical protocols and behavioral measures to produce diagnostic outcomes and examine recent research illustrating a range of benefits of music-based methods at behavioral, cardiorespiratory, and cortical levels using video, electrocardiography, and electroencephalography methods. These latest developments are discussed in the context of evidence-based practice in rehabilitation with clinical populations. © 2014 New York Academy of Sciences.

Circulating complexes between tumour necrosis factor-alpha and etanercept predict long-term efficacy of etanercept in juvenile idiopathic arthritis.

PubMed

Kahn, Robin; Berthold, Elisabet; Gullstrand, Birgitta; Schmidt, Tobias; Kahn, Fredrik; Geborek, Pierre; Saxne, Tore; Bengtsson, Anders A; Månsson, Bengt

2016-04-01

The relationship between tumour necrosis factor-alpha (TNF-α) and drug survival had not been studied in juvenile idiopathic arthritis (JIA), and there were no laboratory tests to predict the long-term efficacy of biological drugs for JIA. We studied whether serum levels of TNF-α, free or bound to etanercept, could predict long-term efficacy of etanercept in children with JIA. We included 41 biologic-naïve patients with JIA who started treatment with etanercept at Skåne University Hospital between 1999 and 2010. Serum taken at the start of treatment and at the six-week follow-up were analysed for TNF-α and the long-term efficacy of etanercept was assessed using the drug survival time. Levels of TNF-α increased significantly at the six-week follow-up, and this was almost exclusively comprised of TNF-α in complex with etanercept. The increase in TNF-α showed a dose-dependent correlation to long-term drug survival (p < 0.01). Increasing levels of circulating TNF-α at treatment initiation predicted long-term efficacy of etanercept in children with JIA, which may have been due to different pathophysiological mechanisms of inflammation. Our result may provide a helpful clinical tool, as high levels of circulating TNF-α/etanercept complexes could be used as a marker for the long-term efficacy of etanercept. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Ruthenium(II) Complexes with 2-Phenylimidazo[4,5-f][1,10]phenanthroline Derivatives that Strongly Combat Cisplatin-Resistant Tumor Cells

NASA Astrophysics Data System (ADS)

Zeng, Leli; Chen, Yu; Liu, Jiangping; Huang, Huaiyi; Guan, Ruilin; Ji, Liangnian; Chao, Hui

2016-01-01

Cisplatin was the first metal-based therapeutic agent approved for the treatment of human cancers, but its clinical activity is greatly limited by tumor drug resistance. This work utilized the parent complex [Ru(phen)2(PIP)]2+ (1) to develop three Ru(II) complexes (2-4) with different positional modifications. These compounds exhibited similar or superior cytotoxicities compared to cisplatin in HeLa, A549 and multidrug-resistant (A549R) tumor cell lines. Complex 4, the most potent member of the series, was highly active against A549R cancer cells (IC50 = 0.8 μM). This complex exhibited 178-fold better activity than cisplatin (IC50 = 142.5 μM) in A549R cells. 3D multicellular A549R tumor spheroids were also used to confirm the high proliferative and cytotoxic activity of complex 4. Complex 4 had the greatest cellular uptake and had a tendency to accumulate in the mitochondria of A549R cells. Further mechanistic studies showed that complex 4 induced A549R cell apoptosis via inhibition of thioredoxin reductase (TrxR), elevated intracellular ROS levels, mitochondrial dysfunction and cell cycle arrest, making it an outstanding candidate for overcoming cisplatin resistance.

Identification of new biosignatures for clinical outcomes in stable coronary artery disease - The study protocol and initial observations of a prospective follow-up study in Taiwan.

PubMed

Leu, Hsin-Bang; Yin, Wei-Hsian; Tseng, Wei-Kung; Wu, Yen-Wen; Lin, Tsung-Hsien; Yeh, Hung-I; Chang, Kuan-Cheng; Wang, Ji-Hung; Wu, Chau-Chung; Chen, Jaw-Wen

2017-01-28

Either classic or novel biomarkers have not been well investigated for clinical outcomes of coronary artery disease (CAD) in Asian people especially ethnic Chinese. We reported here a prospective national-based follow-up study that aims to elucidate the clinical profiles and to identify the new biosignatures (especially the non-lipid profile and inflammatory biomakers) for future clinical outcomes in a sizable cohort of stable CAD patients in Taiwan. A total of 2500 CAD patients under stable condition after successful percutaneous coronary intervention will be enrolled for clinical data collection and blood/urine sampling in northern, southern, western, or eastern part of Taiwan between 2012 and 2017. They will be regularly followed up at least annually for 5 years to assess all cause deaths, hard clinical events (including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), and total cardiovascular events (including hard events, unplanned revascularization procedures, unplanned hospitalization for refractory or unstable angina, and for other causes such as stroke, transient ischemic attack, heart failure, or peripheral arterial occlusive disease). The classic and newly defined biosignatures will be compared in patients with and without clinical events during follow-up. The novel biomarkers will be identified via metabolomics analyses. Additionally, psychological personality and lifestyle data will be incorporated to explore the new dimensional views of the complex mechanisms of the disease. Till December 2014, the initial 1663 patients have been successfully enrolled. Among them, 85.93% are male; 36.22% have type 2 diabetes; 64.82% have hypertension; 56.04% are smokers and 20.44% have a family history of CAD. Their lipid profiles are under contemporary medical control with a mean plasma total cholesterol level of 163.51 ± 36.99 mg/dL and a mean low-density lipoprotein cholesterol level of 95.21 ± 29.98 mg/dL. This nationwide study has successfully started to update the contemporary information and to investigate the potential predictors for clinical outcomes of stable CAD patients in Taiwan. The identification of new biomarkers, lifestyle and psychological personality may help to elucidate the complex mechanisms and provide the novel rational to the individual treatment strategies in Asian especially ethnic Chinese patients with CAD.

Physician Nonadherence With a Hepatitis C Screening Program

PubMed Central

Southern, William N.; Drainoni, Mari-Lynn; Smith, Bryce D.; Koppelman, Elisa; McKee, M. Diane; Christiansen, Cindy L.; Gifford, Allen L.; Weinbaum, Cindy M.; Litwin, Alain H.

2017-01-01

Background Testing for patients at risk for hepatitis C virus (HCV) infection is recommended, but it is unclear whether providers adhere to testing guidelines. We aimed to measure adherence to an HCV screening protocol during a multifaceted continuous intervention. Subjects and Methods Prospective cohort design to examine the associations between patient-level, physician-level, and visit-level characteristics and adherence to an HCV screening protocol. Study participants included all patients with a visit to 1 of the 3 study clinics and the physicians who cared for them. Adherence to the HCV screening protocol and patient-level, physician-level, and visit-level predictors of adherence were measured. Results A total of 8981 patients and 154 physicians were examined. Overall protocol adherence rate was 36.1%. In multivariate analysis, patient male sex (odds ratio [OR] = 1.18), new patient (OR = 1.23), morning visit (OR = 1.32), and patients’ preferred language being non-English (OR = 0.87) were significantly associated with screening adherence. There was a wide variation in overall adherence among physicians (range, 0%–92.4%). Screening adherence continuously declined from 59.1% in week 1 of the study to 13.7% in week 15 (final week). When implementing complex clinical practice guidelines, planners should address physician attitudinal barriers as well as gaps in knowledge to maximize adherence. PMID:24368717

Possible association between Helicobacter pylori infection and nonalcoholic fatty liver disease.

PubMed

Chen, Chang-Xi; Mao, Yu-Shan; Foster, Parker; Zhu, Zhong-Wei; Du, Juan; Guo, Chuan-Yong

2017-03-01

Possible association between Helicobacter pylori infection (HPI) and nonalcoholic fatty liver disease (NAFLD) has been proposed by several studies with inconsistent conclusions. Here, we studied the association between HPI and NAFLD at 3 levels: (i) genetic level; (ii) small molecular level; and (iii) clinical level. Relation data between diseases, genes, and small molecules were acquired from Pathway Studio ResNet Mammalian database. Clinical data were acquired from 2263 elderly South Chinese subjects, including 603 NAFLD patients and 1660 subjects without NAFLD. Results showed that HPI and NAFLD present significantly shared genetic bases (95 genes, p value = 2.5E-72), demonstrating multiple common genetic pathways (enrichment p value ≤ 4.38E-20 for the top 10 pathways). Genetic network analysis suggested that mutual regulation may exist between HPI and NAFLD through 21 out of 95 genes. Furthermore, 85 out of the 95 genes manifested strong interaction with 12 small molecules/drugs that demonstrate effectiveness in treating both diseases. Clinical results showed that HPI rate in the NAFLD group was significantly higher than that in the group without NAFLD (51.9% vs. 43.6%; p value = 4.9E-4). Multivariate logistic regression results supported the observations and suggested that HPI served as a risk factor for NAFLD in the experiment data studied (odds ratio: 1.387, p value = 0.018). Results from this study support the hypothesis that complex biological association may exist between HPI and NAFLD, which partially explains the significant clinical co-incidence in the elderly population of south China.

Developing clinical skills in paediatric dysphagia management using human patient simulation (HPS).

PubMed

Ward, Elizabeth C; Hill, Anne E; Nund, Rebecca L; Rumbach, Anna F; Walker-Smith, Katie; Wright, Sarah E; Kelly, Kris; Dodrill, Pamela

2015-06-01

The use of simulated learning environments to develop clinical skills is gaining momentum in speech-language pathology training programs. The aim of the current study was to examine the benefits of adding Human Patient Simulation (HPS) into the university curriculum in the area of paediatric dysphagia. University students enrolled in a mandatory dysphagia course (n = 29) completed two, 2-hour HPS scenarios: (a) performing a clinical feeding assessment with a medically complex infant; and (b) conducting a clinical swallow examination (CSE) with a child with a tracheostomy. Scenarios covered technical and non-technical skills in paediatric dysphagia management. Surveys relating to students' perceived knowledge, skills, confidence and levels of anxiety were conducted: (a) pre-lectures; (b) post-lectures, but pre-HPS; and (c) post-HPS. A fourth survey was completed following clinical placements with real clients. Results demonstrate significant additive value in knowledge, skills and confidence obtained through HPS. Anxiety about working clinically reduced following HPS. Students rated simulation as very useful in preparing for clinical practice. Post-clinic, students indicated that HPS was an important component in their preparation to work as a clinician. This trial supports the benefits of incorporating HPS as part of clinical preparation for paediatric dysphagia management.

IGF-1, IGFBP-3 and ALS in adult patients with chronic kidney disease.

PubMed

Lepenies, Julia; Wu, Zida; Stewart, Paul M; Strasburger, Christian J; Quinkler, Marcus

2010-04-01

Insulin-like growth factor I (IGF-1) is for the most part bound in a ternary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). This ternary complex is a storage form of IGF-1 in blood and passes not through the renal glomerulus. Little information is available in regard to the components of the ternary complex in adult renal disease. To investigate levels of serum IGF-1, IGFBP-3 and ALS in relation to renal function and extent of proteinuria. We measured IGF-1, IGFBP-3 and ALS concentrations in 137 patients who were investigated due to proteinuria and/or haematuria and/or renal impairment. The patients received renal biopsies and the histological diagnosis was documented. Urinary albumin excretion and relevant clinical parameter were evaluated. IGF-1 showed a highly positive correlation to IGFBP-3 and ALS, and the latter to IGFBP-3. IGF-1, IGFBP-3 and ALS decreased with increasing age. IGF-1 and IGFBP-3 showed no significant change depending on the creatinine clearance. However, ALS decreased with decreasing renal function. In patients with heavy proteinuria ALS levels, but not IGF-1 and IGFBP-3 levels, decreased significantly. Patients with chronic ischaemic renal damage and diabetic glomerulopathy showed higher IGF-1 and IGFBP-3 levels compared to patients with thin glomerular basement membrane disease despite their older age. IGF-1 and IGFBP-3 levels seem to be independent of renal function and severity of proteinuria. However, ALS levels are altered in renal failure and nephrotic syndrome, which may be due to increased renal loss or diminished hepatic production or both. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Dissociative complexity: Antecedents and clinical correlates of a new construct.

PubMed

Briere, John; Dietrich, Anne; Semple, Randye J

2016-09-01

To the extent that dissociation is a multidimensional phenomenon, and given a growing literature on complex posttraumatic outcomes, we hypothesized a new construct: dissociative complexity (DC). DC is defined as the tendency to simultaneously endorse multiple, relatively independent dissociative dimensions into their clinical ranges, and therefore represents the overall breadth or complexity of an individual's dissociative response. DC was evaluated in general population and prison participants using the Multiscale Dissociation Inventory (MDI; Briere, 2002). DC was higher among prisoners and women, and, as hypothesized, was associated with cumulative trauma and serious comorbidities (suicidality and substance abuse), even when controlling for generally elevated dissociation. DC appears to be a meaningful clinical construct that is phenomenologically and empirically different from a unidimensional index of dissociative severity. DC may serve as a clinical marker for multiple trauma exposures, complex dissociative outcomes, and risk of problematic comorbidities. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Understanding factors associated with the translation of cardiovascular research: a multinational case study approach

PubMed Central

2014-01-01

Background Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. Methods We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Results Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of factors behind research translation that can arise in a single case. Conclusions We can systematically assess research impacts and use the findings to promote translation. Research funders can justify funding research of diverse types, but they should not assume academic impacts are proxies for wider impacts. They should encourage researchers to consider pathways towards impact and engage potential research users in research processes. PMID:24755187

Understanding factors associated with the translation of cardiovascular research: a multinational case study approach.

PubMed

Wooding, Steven; Hanney, Stephen R; Pollitt, Alexandra; Grant, Jonathan; Buxton, Martin J

2014-04-21

Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of factors behind research translation that can arise in a single case. We can systematically assess research impacts and use the findings to promote translation. Research funders can justify funding research of diverse types, but they should not assume academic impacts are proxies for wider impacts. They should encourage researchers to consider pathways towards impact and engage potential research users in research processes.

Anti-Aß immunotherapy in Alzheimer's disease; relevance of transgenic mouse studies to clinical trials

PubMed Central

Wilcock, Donna M.; Colton, Carol A.

2009-01-01

Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the Aß peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the other pathologies of Alzheimer's, namely neurofibrillary tangles and neurodegeneration, as well as the clinical dementia. One such therapy that has attracted significant attention is anti-Aß immunotherapy. First described in 1999, immunotherapy uses anti-Aß antibodies to lower brain amyloid levels. Active immunization, in which Aß is combined with an adjuvant to stimulate an immune response producing antibodies and passive immunization, in which antibodies are directly injected, were shown to lower brain amyloid levels and improve cognition in multiple transgenic mouse models. Mechanisms of action were studied in these mice and revealed a complex set of mechanisms that depended on the type of antibody used. When active immunization advanced to clinical trials a subset of patients developed meningoencephalitis; an event not predicted in mouse studies. However, it was suspected that a T-cell response due to the type of adjuvant used was the cause of the meningoencephalitis and studies in mice indicated alternative methods of vaccination. Passive immunization has also advanced to phase III clinical trials on the basis of successful transgenic mouse studies. Reports from the active immunization clinical trial indicated that, indeed, amyloid levels in brain were reduced. While APP transgenic mouse models are useful in studying amyloid pathology these mice do not generate significant tau pathology or neuron loss. Continued development of new mouse models that do generate all of these pathologies will be critical in more accurately testing therapeutics and predicting the clinical outcome of such therapeutics. PMID:19096156

Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

PubMed

Velasco, Cesar; Pérez, Inaki; Podzamczer, Daniel; Llibre, Josep Maria; Domingo, Pere; González-García, Juan; Puig, Inma; Ayala, Pilar; Martín, Mayte; Trilla, Antoni; Lázaro, Pablo; Gatell, Josep Maria

2016-03-01

The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases.

PubMed

da Silva-Boghossian, Carina Maciel; do Souto, Renata Martins; Luiz, Ronir R; Colombo, Ana Paula Vieira

2011-09-01

Pathogens related to systemic infections have been detected in the periodontal microbiota. The relationship amongst these pathogens, periodontal bacteria and periodontal clinical status is poorly understood. This study evaluated the association amongst red complex, A. actinomycetemcomitans (A.a) and non-oral pathogenic bacteria in subjects with good periodontal health (PH), gingivitis (G), chronic (CP) and aggressive (AP) periodontitis. Subgingival biofilm samples were obtained from 51 PH, 42 G, 219 CP and 90 AP subjects. The presence and levels of A.a, red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola), Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by DNA probes and DNA-DNA hybridization technique. CP and AP subjects presented significantly higher prevalence and levels of A.a, red complex and A. baumannii than G and PH individuals (p<0.01), whereas S. aureus was detected in lower frequency and counts in AP as compared to the other groups (p<0.001). The predictor variables age, prevalence of red complex, and the presence of A. baumannii and P. aeruginosa were strongly associated with the frequency of sites with PD and CAL ≥5 mm. Increasing age (OR 1.08), high frequency of red complex (OR 6.10), and the presence of A.a with P. aeruginosa (OR 1.90) were associated with periodontal disease (p<0.001). Subjects harbouring a high prevalence of A.a, A. baumannii, and red complex with P. aeruginosa were more likely to have AP than CP (p<0.001). Putative periodontal pathogens and non-oral bacteria alone or in association were strongly associated with periodontitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mothers of IVF twins: the mediating role of employment and social coping resources in maternal stress.

PubMed

Baor, Liora; Soskolne, Varda

2012-01-01

Twin pregnancies and births resulting from assisted reproductive technologies have been associated with adverse perinatal outcomes and maternal health complications leading to psychologically complex parenting. In the current study the authors assess the prevalence of clinical levels of maternal stress among mothers of twins resulting from in vitro fertilization and examine the association of social coping resources with three maternal stress sub-scales. During the years 2003-2005, 88 primiparous Israeli mothers of in vitro fertilization-conceived twins provided socio-demographic data during their third trimester of pregnancy, and at 6 months after birth provided data on delivery and medical condition of infants, coping resources (social support and marital quality), and a maternal stress scale. Forty-one percent of the mothers reached a clinically significant level of maternal stress. Social support and maternal employment were the most significant variables associated with experience of the stress in the early stages of adaptation to mothering in vitro fertilization twins. Primiparous mothers of in vitro fertilization twins are vulnerable to maternal stress in early stages of adaptation to the maternal role, some of whom reach clinical levels that may require professional interventions. Unemployed mothers with low social support were the most susceptible to the deleterious effects of in vitro fertilization treatment.

Raising attention to attention deficit hyperactivity disorder in schizophrenia

PubMed Central

Pallanti, Stefano; Salerno, Luana

2015-01-01

Schizophrenia and attention deficit hyperactivity disorder (ADHD) are two psychiatric disorders with a negative impact on quality of life of individuals affected. Although they are classified into distinct disorders categories, attentional dysfunction is considered as a core feature in both conditions, either at the clinical then pathophysiological level. Beyond the obvious clinical overlap between these disorders, the Research Domain Criteria approach might offer an interesting perspective for disentangling common circuits underpinning both disorders. Hence, we review evidences regarding the overlap between schizophrenia and ADHD, at the clinical level, and at the level of underlying brain mechanisms. The evidence regarding the influence of environmental risk factors in the emergence of both disorders, and their developmental trajectories is also reviewed. Among these, we will try to elucidate the complex relationship between stimulants use and psychotic symptoms, discussing the potential role of ADHD medication in inducing psychosis or in exacerbating it. We aim that, taken together, these findings may promote further investigation with important implications both for clinicians and research. In fact, considering the amounting evidence on the overlap between schizophrenia and ADHD, the delineation of their boundaries might help in the decision for diagnosis and treatment. Moreover, it may help to promote interventions focused on the prevention of both schizophrenia and ADHD, by the reduction of recognized environmental risk factors. PMID:25815254

Total and acylated ghrelin in liver cirrhosis: correlation with clinical and nutritional status.

PubMed

El-Shehaby, Amal M; Obaia, Eman M; Alwakil, Sahar S; Hiekal, Ahmed A

2010-07-01

The pathogenesis of anorexia in cirrhotic patients is complex and the appetite-modulating hormone ghrelin could be involved. Acylated ghrelin is the biologically active form that modifies insulin sensitivity and body composition. The aim of the present study was to compare acylated and total ghrelin concentration in patients with liver cirrhosis and to investigate the possible relationship between ghrelin and clinical and nutritional parameters. Sixty patients with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twenty healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls. Fasting levels of total, acylated ghrelin, leptin, TNF-alpha and insulin were measured in all subjects, in addition, clinical and nutrition parameters were assessed. In cirrhotic patients, plasma levels of both acylated and total ghrelin were significantly higher than those in the controls. The mean plasma acylated ghrelin levels were significantly higher in Child C cirrhosis compared to Child A and B. Ghrelin (total and acylated) were negatively correlated with leptin in cirrhotic patients confirming the fact that leptin acts as a physiological counterpart of ghrelin. Nutritional and metabolic abnormalities in cirrhotic patients may be dependent on the changes in the ghrelin/leptin systems, mainly the acylated form of ghrelin.

Construction of graphic symbol utterances by children, teenagers, and adults: the effect of structure and task demands.

PubMed

Trudeau, Natacha; Sutton, Ann; Dagenais, Emmanuelle; de Broeck, Sophie; Morford, Jill

2007-10-01

This study investigated the impact of syntactic complexity and task demands on construction of utterances using picture communication symbols by participants from 3 age groups with no communication disorders. Participants were 30 children (7;0 [years;months] to 8;11), 30 teenagers (12;0 to 13;11), and 30 adults (18 years and above). All participants constructed graphic symbol utterances to describe photographs presented with spoken French stimuli. Stimuli included simple and complex (object relative and subject relative) utterances describing the photographs, which were presented either 1 at a time (neutral condition) or in an array of 4 (contrast condition). Simple utterances lead to more uniform response patterns than complex utterances. Among complex utterances, subject relative sentences appeared more difficult to convey. Increasing the need for message clarity (i.e., contrast condition) elicited changes in the production of graphic symbol sequences for complex propositions. The effects of syntactic complexity and task demands were more pronounced for children. Graphic symbol utterance construction appears to involve more than simply transferring spoken language skills. One possible explanation is that this type of task requires higher levels of metalinguistic ability. Clinical implications and directions for further research are discussed.

Case study method and problem-based learning: utilizing the pedagogical model of progressive complexity in nursing education.

PubMed

McMahon, Michelle A; Christopher, Kimberly A

2011-08-19

As the complexity of health care delivery continues to increase, educators are challenged to determine educational best practices to prepare BSN students for the ambiguous clinical practice setting. Integrative, active, and student-centered curricular methods are encouraged to foster student ability to use clinical judgment for problem solving and informed clinical decision making. The proposed pedagogical model of progressive complexity in nursing education suggests gradually introducing students to complex and multi-contextual clinical scenarios through the utilization of case studies and problem-based learning activities, with the intention to transition nursing students into autonomous learners and well-prepared practitioners at the culmination of a nursing program. Exemplar curricular activities are suggested to potentiate student development of a transferable problem solving skill set and a flexible knowledge base to better prepare students for practice in future novel clinical experiences, which is a mutual goal for both educators and students.

From genotype to phenotype: genetics and medical practice in the new millennium.

PubMed Central

Weatherall, D

1999-01-01

The completion of the human genome project will provide a vast amount of information about human genetic diversity. One of the major challenges for the medical sciences will be to relate genotype to phenotype. Over recent years considerable progress has been made in relating the molecular pathology of monogenic diseases to the associated clinical phenotypes. Studies of the inherited disorders of haemoglobin, notably the thalassaemias, have shown how even in these, the simplest of monogenic diseases, there is remarkable complexity with respect to their phenotypic expression. Although studies of other monogenic diseases are less far advanced, it is clear that the same level of complexity will exist. This information provides some indication of the difficulties that will be met when trying to define the genes that are involved in common multigenic disorders and, in particular, in trying to relate disease phenotypes to the complex interactions between many genes and multiple environmental factors. PMID:10670020

Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry and their trace detection in complex matrices by gas chromatography-tandem mass spectrometry.

PubMed

Fox, A

1999-05-28

Bacterial cellular polysaccharides are composed of a variety of sugar monomers. These sugars serve as chemical markers to identify specific species or genera or to determine their physiological status. Some of these markers can also be used for trace detection of bacteria or their constituents in complex clinical or environmental matrices. Analyses are performed, in our hands, employing hydrolysis followed by the alditol acetate derivatization procedure. Substantial improvements have been made to sample preparation including simplification and computer-controlled automation. For characterization of whole cell bacterial hydrolysates, sugars are analyzed by gas chromatography-mass spectrometry (GC-MS). Simple chromatograms are generated using selected ion monitoring (SIM). Using total ion GC-MS, sugars can be readily identified. In more complex clinical and environmental samples, markers for bacteria are present at sufficiently low concentrations that more advanced instrumentation, gas chromatography-tandem mass spectrometry (GC-MS-MS), is preferred for optimal analysis. Using multiple reaction monitoring, MS-MS is used (replacing more conventional SIM) to ignore extraneous chromatographic peaks. Triple quadrupole and ion trap GC-MS-MS instruments have both been used successfully. Absolute chemical identification of sugar markers at trace levels is achieved, using MS-MS, by the product spectrum.

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

PubMed

Agosti, J M; Coombs, R W; Collier, A C; Paradise, M A; Benedetti, J K; Jaffe, H S; Corey, L

1992-05-01

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

The Complexity of Multiple Contraceptive Method Use and the Anxiety That Informs It: Implications for Theory and Practice.

PubMed

Frohwirth, Lori; Blades, Nakeisha; Moore, Ann M; Wurtz, Heather

2016-11-01

Despite clinical guidelines and national data describing the use of one contraceptive method as the best and most common way to prevent unintended pregnancy, limited evidence indicates a more complex picture of actual contraceptive practice. Face-to-face in-depth interviews were conducted in November of 2013 with a sample of women from two cities in the United States (n = 52). The interviews explored the ways participants used contraception to protect themselves from unintended pregnancy over the past 12 months. Most respondents reported using multiple methods, many of which are considered to be less-effective, within this timeframe. The practice of combining methods in order to increase one's level of protection from pregnancy was prevalent, and was mainly enacted in two ways: by backing up inconsistent method use with other methods and by "buttressing" methods. These practices were found to be more common, and more complex, than previously described in the literature. These behaviors were mainly informed by a deep anxiety about both the efficacy of contraceptive methods, and about respondents' own perceived ability to prevent pregnancy. These findings challenge prevailing assumptions about women's contraceptive method use and have implications for clinical contraceptive counseling practice.

Butyrylcholinesterase for protection from organophosphorus poisons; catalytic complexities and hysteretic behavior

PubMed Central

Masson, Patrick; Lockridge, Oksana

2009-01-01

Butyrylcholinesterase is a promiscuous enzyme that displays complex kinetic behavior. It is toxicologically important because it detoxifies organophosphorus poisons (OP) by making a covalent bond with the OP. The OP and the butyrylcholinesterase are both inactivated in the process. Inactivation of butyrylcholinesterase has no adverse effects. However inactivation of acetylcholinesterase in nerve synapses can be lethal. OP-inhibited butyrylcholinesterase and acetylcholinesterase can be reactivated with oximes provided the OP has not aged. Strategies for preventing the toxicity of OP include a) treatment with an OP scavenger, b) reaction of nonaged enzyme with oximes, c) reactivation of aged enzyme, d) slowing down aging with peripheral site ligands, and e) design of mutants that rapidly hydrolyze OP. Option (a) has progressed through phase I clinical trials with human butyrylcholinesterase. Option (b) is in routine clinical use. The others are at the basic research level. Butyrylcholinesterase displays complex kinetic behavior including activation by positively charged esters, ability to hydrolyze amides, and a lag time (hysteresis) preceding hydrolysis of benzoylcholine and N-methyl indoxyl acetate. Mass spectrometry has identified new OP binding motifs on tyrosine and lysine in proteins that have no active site serine. It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine. PMID:20004171

The impact of network medicine in gastroenterology and hepatology.

PubMed

Baffy, György

2013-10-01

In the footsteps of groundbreaking achievements made by biomedical research, another scientific revolution is unfolding. Systems biology draws from the chaos and complexity theory and applies computational models to predict emerging behavior of the interactions between genes, gene products, and environmental factors. Adaptation of systems biology to translational and clinical sciences has been termed network medicine, and is likely to change the way we think about preventing, predicting, diagnosing, and treating complex human diseases. Network medicine finds gene-disease associations by analyzing the unparalleled digital information discovered and created by high-throughput technologies (dubbed as "omics" science) and links genetic variance to clinical disease phenotypes through intermediate organizational levels of life such as the epigenome, transcriptome, proteome, and metabolome. Supported by large reference databases, unprecedented data storage capacity, and innovative computational analysis, network medicine is poised to find links between conditions that were thought to be distinct, uncover shared disease mechanisms and key drivers of the pathogenesis, predict individual disease outcomes and trajectories, identify novel therapeutic applications, and help avoid off-target and undesirable drug effects. Recent advances indicate that these perspectives are increasingly within our reach for understanding and managing complex diseases of the digestive system. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nicotine dependence and psychological distress: outcomes and clinical implications in smoking cessation

PubMed Central

Cosci, Fiammetta; Pistelli, Francesco; Lazzarini, Nicola; Carrozzi, Laura

2011-01-01

Nicotine dependence is characteristically a chronic and relapsing disease. Although 75%–85% of smokers would like to quit, and one-third make at least three serious lifetime attempts, less than 50% of smokers succeed in stopping before the age of 60. Relevant and complex factors contributing to sustained cigarette consumption, and strongly implicated in the clinical management of smokers, are the level of nicotine dependence and psychological distress. In this review of the literature, these two factors will be examined in detail to show how they may affect smoking cessation outcome and to encourage clinicians to assess patients so they can offer tailored support in quitting smoking. PMID:22114542

Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference.

PubMed

Krueger, Darcy A; Northrup, Hope

2013-10-01

Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations and progression can be life-threatening with significant impact on cost and quality of life. Current surveillance and management practices are highly variable among region and country, reflective of the fact that last consensus recommendations occurred in 1998 and an updated, comprehensive standard is lacking that incorporates the latest scientific evidence and current best clinical practices. The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important clinical management implications and was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation accordingly. The updated consensus recommendations for clinical surveillance and management in tuberous sclerosis complex are summarized here. The recommendations are relevant to the entire lifespan of the patient, from infancy to adulthood, including both individuals where the diagnosis is newly made as well as individuals where the diagnosis already is established. The 2012 International Tuberous Sclerosis Complex Consensus Recommendations provide an evidence-based, standardized approach for optimal clinical care provided for individuals with tuberous sclerosis complex. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

What predicts performance during clinical psychology training?

PubMed Central

Scior, Katrina; Bradley, Caroline E; Potts, Henry W W; Woolf, Katherine; de C Williams, Amanda C

2014-01-01

Objectives While the question of who is likely to be selected for clinical psychology training has been studied, evidence on performance during training is scant. This study explored data from seven consecutive intakes of the UK's largest clinical psychology training course, aiming to identify what factors predict better or poorer outcomes. Design Longitudinal cross-sectional study using prospective and retrospective data. Method Characteristics at application were analysed in relation to a range of in-course assessments for 274 trainee clinical psychologists who had completed or were in the final stage of their training. Results Trainees were diverse in age, pre-training experience, and academic performance at A-level (advanced level certificate required for university admission), but not in gender or ethnicity. Failure rates across the three performance domains (academic, clinical, research) were very low, suggesting that selection was successful in screening out less suitable candidates. Key predictors of good performance on the course were better A-levels and better degree class. Non-white students performed less well on two outcomes. Type and extent of pre-training clinical experience on outcomes had varied effects on outcome. Research supervisor ratings emerged as global indicators and predicted nearly all outcomes, but may have been biased as they were retrospective. Referee ratings predicted only one of the seven outcomes examined, and interview ratings predicted none of the outcomes. Conclusions Predicting who will do well or poorly in clinical psychology training is complex. Interview and referee ratings may well be successful in screening out unsuitable candidates, but appear to be a poor guide to performance on the course. Practitioner points While referee and selection interview ratings did not predict performance during training, they may be useful in screening out unsuitable candidates at the application stage High school final academic performance was the best predictor of good performance during clinical psychology training The findings are derived from seven cohorts of one training course, the UK's largest; they cannot be assumed to generalize to all training courses PMID:24206117

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.

IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

PubMed Central

Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C

1987-01-01

To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

CaP CURE Initiatives and Projects

PubMed Central

Soule, Howard R

2003-01-01

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization’s Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE’s efforts have resulted in a significant increase in federal funding of prostate cancer research programs. PMID:16986049

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

PubMed

Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

2016-01-01

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

PubMed

Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

2014-01-01

Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment.

Cardiovascular disease in women and noncontraceptive use of hormones: a feminist analysis.

PubMed

MacPherson, K I

1992-06-01

Cardiovascular disease (CVD) in women is being defined by biomedical researchers and physicians as part of the menopausal syndrome. Postmenopausal lowered levels of estrogen are presented as a prime cause of changes in cholesterol levels that are a risk factor for CVD. The biomedical model and hormone debate are described and analyzed, followed by a feminist perspective of CVD. This includes new federal policies that support CVD research. Nurses are encouraged to present a broader picture of CVD and its risks than that presented by the biomedical model and to empower women's understanding of this complex health issue through educational, clinical, and research endeavors.

CURRENT CONCEPTS IN BIOMECHANICAL INTERVENTIONS FOR PATELLOFEMORAL PAIN

PubMed Central

Meira, Erik P.

2016-01-01

Patellofemoral pain (PFP) has historically been a complex and enigmatic issue. Many of the factors thought to relate to PFP remain after patients' symptoms have resolved making their clinical importance difficult to determine. The tissue homeostasis model proposed by Dye in 2005 can assist with understanding and implementing biomechanical interventions for PFP. Under this model, the goal of interventions for PFP should be to re-establish patellofemoral joint (PFJ) homeostasis through a temporary alteration of load to the offended tissue, followed by incrementally restoring the envelope of function to the baseline level or higher. High levels of PFJ loads, particularly in the presence of an altered PFJ environment, are thought to be a factor in the development of PFP. Clinical interventions often aim to alter the biomechanical patterns that are thought to result in elevated PFJ loads while concurrently increasing the load tolerance capabilities of the tissue through therapeutic exercise. Biomechanics may play a role in PFJ load modification not only when addressing proximal and distal components, but also when considering the involvement of more local factors such as the quadriceps musculature. Biomechanical considerations should consider the entire kinetic chain including the hip and the foot/ankle complex, however the beneficial effects of these interventions may not be the result of long-term biomechanical changes. Biomechanical alterations may be achieved through movement retraining, but the interventions likely need to be task-specific to alter movement patterns. The purpose of this commentary is to describe biomechanical interventions for the athlete with PFP to encourage a safe and complete return to sport. Level of Evidence 5 PMID:27904791

Coding OSICS sports injury diagnoses in epidemiological studies: does the background of the coder matter?

PubMed Central

Finch, Caroline F; Orchard, John W; Twomey, Dara M; Saad Saleem, Muhammad; Ekegren, Christina L; Lloyd, David G; Elliott, Bruce C

2014-01-01

Objective To compare Orchard Sports Injury Classification System (OSICS-10) sports medicine diagnoses assigned by a clinical and non-clinical coder. Design Assessment of intercoder agreement. Setting Community Australian football. Participants 1082 standardised injury surveillance records. Main outcome measurements Direct comparison of the four-character hierarchical OSICS-10 codes assigned by two independent coders (a sports physician and an epidemiologist). Adjudication by a third coder (biomechanist). Results The coders agreed on the first character 95% of the time and on the first two characters 86% of the time. They assigned the same four-digit OSICS-10 code for only 46% of the 1082 injuries. The majority of disagreements occurred for the third character; 85% were because one coder assigned a non-specific ‘X’ code. The sports physician code was deemed correct in 53% of cases and the epidemiologist in 44%. Reasons for disagreement included the physician not using all of the collected information and the epidemiologist lacking specific anatomical knowledge. Conclusions Sports injury research requires accurate identification and classification of specific injuries and this study found an overall high level of agreement in coding according to OSICS-10. The fact that the majority of the disagreements occurred for the third OSICS character highlights the fact that increasing complexity and diagnostic specificity in injury coding can result in a loss of reliability and demands a high level of anatomical knowledge. Injury report form details need to reflect this level of complexity and data management teams need to include a broad range of expertise. PMID:22919021

Direct immunofluorescence of normal skin in rheumatoid arthritis.

PubMed

Fitzgerald, O M; Barnes, L; Woods, R; McHugh, L; Barry, C; O'Loughlin, S

1985-11-01

The clinical significance of previously described immunoglobulin and complement deposition in the superficial dermal vessel walls of patients with rheumatoid arthritis is unknown. In the present study, skin biopsies were obtained from the normal forearm and buttock of 48 unselected patients with rheumatoid arthritis and were examined by direct immunofluorescence (IF) for the presence of immunoglobulin (IgG,A,M) and complement (C3) in the vessel walls. Deposits of C3, IgM or IgG were detected in 10 patients. Five patients had deposits at the forearm sample alone, four patients had deposits at both biopsy sites, while one patient was positive at the buttock alone. Clinical features were similar in patients with and without vessel IF. However, patients with IF were significantly more seropositive with lower levels of complement and raised levels of serum IgA and IgM. There was also an increased level of circulating IgG immune complexes in these patients. Further analysis following exclusion of seronegative patients revealed similar results. This study suggests that the presence of vessel IF identifies a subgroup of patients who have evidence of more severe immunological disturbance.

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes

PubMed Central

Pereira, Bernard; Chin, Suet-Feung; Rueda, Oscar M.; Vollan, Hans-Kristian Moen; Provenzano, Elena; Bardwell, Helen A.; Pugh, Michelle; Jones, Linda; Russell, Roslin; Sammut, Stephen-John; Tsui, Dana W. Y.; Liu, Bin; Dawson, Sarah-Jane; Abraham, Jean; Northen, Helen; Peden, John F.; Mukherjee, Abhik; Turashvili, Gulisa; Green, Andrew R.; McKinney, Steve; Oloumi, Arusha; Shah, Sohrab; Rosenfeld, Nitzan; Murphy, Leigh; Bentley, David R.; Ellis, Ian O.; Purushotham, Arnie; Pinder, Sarah E.; Børresen-Dale, Anne-Lise; Earl, Helena M.; Pharoah, Paul D.; Ross, Mark T.; Aparicio, Samuel; Caldas, Carlos

2016-01-01

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. PMID:27161491

Novel Application of a Reverse Triage Protocol Providing Increased Access to Care in an Outpatient, Primary Care Clinic Setting.

PubMed

Sacino, Amanda N; Shuster, Jonathan J; Nowicki, Kamil; Carek, Peter J; Wegman, Martin P; Listhaus, Alyson; Gibney, Joseph M; Chang, Ku-Lang

2016-02-01

As the number of patients with access to care increases, outpatient clinics will need to implement innovative strategies to maintain or enhance clinic efficiency. One viable alternative involves reverse triage. A reverse triage protocol was implemented during a student-run free clinic. Each patient's chief complaint(s) were obtained at the beginning of the clinic session and ranked by increasing complexity. "Complexity" was defined as the subjective amount of time required to provide a full, thorough evaluation of a patient. Less complex cases were prioritized first since they could be expedited through clinic processing and allow for more time and resources to be dedicated to complex cases. Descriptive statistics were used to characterize and summarize the data obtained. Categorical variables were analyzed using chi-square. A time series analysis of the outcome versus centered time in weeks was also conducted. The average number of patients seen per clinic session increased by 35% (9.5 versus 12.8) from pre-implementation of the reverse triage protocol to 6 months after the implementation of the protocol. The implementation of a reverse triage in an outpatient setting significantly increased clinic efficiency as noted by a significant increase in the number of patients seen during a clinic session.

Thermalism in Argentina. Alternative or complementary dermatologic therapy.

PubMed

Ubogui, J; Stengel, F M; Kien, M C; Sevinsky, L; Rodríguez Lupo, L

1998-11-01

Our study took place in the region of the Copahue Volcano in the Andes Mountain range, 1900 m above sea level. Fifty-five patients who came to the Copahue Thermal Basin Complex (Neuquén, Argentina) for treatment of psoriasis vulgaris were clinically evaluated for participation in this study. Thermal products--waters, mud, and/or algae--were the only therapeutic agents used, except for bland emollients for xerosis. Treatment for brief periods (10 +/- 3 days) resulted in notable improvement.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

PubMed Central

Siefker-Radtke, Arlene; Zhang, Xin-qiao; Guo, Charles C; Shen, Yu; Pirollo, Kathleen F; Sabir, Sharjeel; Leung, Chris; Leong-Wu, Cindy; Ling, Chi-Ming; Chang, Esther H; Millikan, Randall E; Benedict, William F

2016-01-01

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy. PMID:27480598

Using video-reflexive ethnography to capture the complexity of leadership enactment in the healthcare workplace.

PubMed

Gordon, Lisi; Rees, Charlotte; Ker, Jean; Cleland, Jennifer

2017-12-01

Current theoretical thinking asserts that leadership should be distributed across many levels of healthcare organisations to improve the patient experience and staff morale. However, much healthcare leadership education focusses on the training and competence of individuals and little attention is paid to the interprofessional workplace and how its inherent complexities might contribute to the emergence of leadership. Underpinned by complexity theory, this research aimed to explore how interprofessional healthcare teams enact leadership at a micro-level through influential acts of organising. A whole (interprofessional) team workplace-based study utilising video-reflexive ethnography occurred in two UK clinical sites. Thematic framework analyses of the video data (video-observation and video-reflexivity sessions) were undertaken, followed by in-depth analyses of human-human and human-material interactions. Data analysis revealed a complex interprofessional environment where leadership is a dynamic process, negotiated and renegotiated in various ways throughout interactions (both formal and informal). Being able to "see" themselves at work gave participants the opportunity to discuss and analyse their everyday leadership practices and challenge some of their sometimes deeply entrenched values, beliefs, practices and assumptions about healthcare leadership. These study findings therefore indicate a need to redefine the way that medical and healthcare educators facilitate leadership development and argue for new approaches to research which shifts the focus from leaders to leadership.

Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

PubMed

Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

2018-03-22

Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement with key stakeholders at international and national levels enabled the Sponsoring Entities to address challenges by aligning the study design with the requirements of health and regulatory agencies and to understand and address healthcare infrastructure needs prior to trial initiation. Local stakeholder engagement, including community members, study participants, and family enabled the investigators to address challenges by ensuring that study design and conduct were adapted to local considerations and ensuring accurate information about the study aims was shared with the public. ClinicalTrials.gov, ID: NCT01103063 . Registered on 7 April 2010.

Catalytic superoxide scavenging by metal complexes of the calcium chelator EGTA and contrast agent EHPG.

PubMed

Fisher, Anna E O; Hague, Theresa A; Clarke, Charlotte L; Naughton, Declan P

2004-10-08

Metal ion chelators widely used in experimental protocols and clinical diagnosis are generally assumed to be inert. We previously reported that the ubiquitous chelator EDTA has high levels of superoxide suppressing activity. Here, we report that the common chelators calcium chelator EGTA and contrast agent EHPG have significant activities in suppressing superoxide levels depending on the nature of metal ion chelated. The most active species is Mn(II)-EGTA which exhibited an IC50 value of 0.19 microM for superoxide destruction. In addition, IC50 values for Mn(II)-EHPG and 2Cu(II)-EGTA were 0.69 and 0.60 microM, respectively. In conclusion, Mn(II) and Cu(II) complexes of the common chelators EGTA and EHPG exhibit considerable superoxide scavenging activities. Caution should be employed in their use in biological systems where superoxide has a key role and they may be useful for the development of catalytic anti-oxidants. Copyright 2004 Elsevier Inc.

Teaching complex trauma care in a curriculum challenges critical thinking and clinical judgment--how nurses can help.

PubMed

West, Margaret Mary; Bross, Gina; Snyder, Melissa

2007-01-01

Incorporating complex content into a nursing curriculum presents students with the knowledge and thinking skills necessary to enter a career in nursing. A level 1 trauma center is a prefect environment to advance these thinking skills. Nurses act as professional role models and teachers as they clarify and explain their thinking to a student. When experienced nurses show invitational behaviors to students and share their knowledge with them, they ignite a strong desire within the student to progress. Caring, communication, and inclusion are key components that synergize the teaching/learning experience. The development of critical thinking is a continuous process that is best achieved through collaboration between the student, faculty, and professional, experienced nurses.

Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency☆

PubMed Central

Simon, Mariella T.; Ng, Bobby G.; Friederich, Marisa W.; Wang, Raymond Y.; Boyer, Monica; Kircher, Martin; Collard, Renata; Buckingham, Kati J.; Chang, Richard; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Van Hove, Johan L.K.; Freeze, Hudson H.; Abdenur, Jose E.

2017-01-01

We report the clinical, biochemical, and molecular findings in two brothers with encephalopathy and multi-systemic disease. Abnormal transferrin glycoforms were suggestive of a type I congenital disorder of glycosylation (CDG). While exome sequencing was negative for CDG related candidate genes, the testing revealed compound heterozygous mutations in the mitochondrial elongation factor G gene (GFM1). One of the mutations had been reported previously while the second, novel variant was found deep in intron 6, activating a cryptic splice site. Functional studies demonstrated decreased GFM1 protein levels, suggested disrupted assembly of mitochondrial complexes III and V and decreased activities of mitochondrial complexes I and IV, all indicating combined OXPHOS deficiency. PMID:28216230

Early Tibiotalocalcaneal Arthrodesis Intramedullary Nail for Treatment of a Complex Tibial Pilon Fracture (AO/OTA 43-C).

PubMed

Hsu, Andrew R; Szatkowski, Jan P

2015-06-01

Management of severely comminuted, complete articular tibial pilon fractures (AO/OTA 43-C) remains a challenge, with few treatment options providing good clinical outcomes. Open reduction and internal fixation of the tibial plafond, tibiotalar arthrodesis, and salvage hindfoot reconstruction procedures are all associated with surgical complications and functional limitations. In this report, we present a case of a complex pilon fracture in a patient with multiple medical comorbidities and socioeconomic disadvantages that was successfully and acutely treated with a retrograde tibiotalocalcaneal hindfoot arthrodesis nail. At final follow-up examination, the patient had decreased pain, a stable plantigrade foot, and could ambulate with normal shoes without any assistive devices. Therapeutic, Level IV: Case series. © 2014 The Author(s).

A novel complete-case analysis to determine statistical significance between treatments in an intention-to-treat population of randomized clinical trials involving missing data.

PubMed

Liu, Wei; Ding, Jinhui

2018-04-01

The application of the principle of the intention-to-treat (ITT) to the analysis of clinical trials is challenged in the presence of missing outcome data. The consequences of stopping an assigned treatment in a withdrawn subject are unknown. It is difficult to make a single assumption about missing mechanisms for all clinical trials because there are complicated reactions in the human body to drugs due to the presence of complex biological networks, leading to data missing randomly or non-randomly. Currently there is no statistical method that can tell whether a difference between two treatments in the ITT population of a randomized clinical trial with missing data is significant at a pre-specified level. Making no assumptions about the missing mechanisms, we propose a generalized complete-case (GCC) analysis based on the data of completers. An evaluation of the impact of missing data on the ITT analysis reveals that a statistically significant GCC result implies a significant treatment effect in the ITT population at a pre-specified significance level unless, relative to the comparator, the test drug is poisonous to the non-completers as documented in their medical records. Applications of the GCC analysis are illustrated using literature data, and its properties and limits are discussed.

Primary care practice organization influences colorectal cancer screening performance.

PubMed

Yano, Elizabeth M; Soban, Lynn M; Parkerton, Patricia H; Etzioni, David A

2007-06-01

To identify primary care practice characteristics associated with colorectal cancer (CRC) screening performance, controlling for patient-level factors. Primary care director survey (1999-2000) of 155 VA primary care clinics linked with 38,818 eligible patients' sociodemographics, utilization, and CRC screening experience using centralized administrative and chart-review data (2001). Practices were characterized by degrees of centralization (e.g., authority over operations, staffing, outside-practice influence); resources (e.g., sufficiency of nonphysician staffing, space, clinical support arrangements); and complexity (e.g., facility size, academic status, managed care penetration), adjusting for patient-level covariates and contextual factors. Chart-based evidence of CRC screening through direct colonoscopy, sigmoidoscopy, or consecutive fecal occult blood tests, eliminating cases with documented histories of CRC, polyps, or inflammatory bowel disease. After adjusting for sociodemographic characteristics and health care utilization, patients were significantly more likely to be screened for CRC if their primary care practices had greater autonomy over the internal structure of care delivery (p<.04), more clinical support arrangements (p<.03), and smaller size (p<.001). Deficits in primary care clinical support arrangements and local autonomy over operational management and referral procedures are associated with significantly lower CRC screening performance. Competition with hospital resource demands may impinge on the degree of internal organization of their affiliated primary care practices.

Client satisfaction with reproductive health-care quality: integrating business approaches to modeling and measurement.

PubMed

Alden, Dana L; Do, Mai Hoa; Bhawuk, Dharm

2004-12-01

Health-care managers are increasingly interested in client perceptions of clinic service quality and satisfaction. While tremendous progress has occurred, additional perspectives on the conceptualization, modeling and measurement of these constructs may further assist health-care managers seeking to provide high-quality care. To that end, this study draws on theories from business and health to develop an integrated model featuring antecedents to and consequences of reproductive health-care client satisfaction. In addition to developing a new model, this study contributes by testing how well Western-based theories of client satisfaction hold in a developing, Asian country. Applied to urban, reproductive health clinic users in Hanoi, Vietnam, test results suggest that hypothesized antecedents such as pre-visit expectations, perceived clinic performance and how much performance exceeds expectations impact client satisfaction. However, the relative importance of these predictors appears to vary depending on a client's level of service-related experience. Finally, higher levels of client satisfaction are positively related to future clinic use intentions. This study demonstrates the value of: (1) incorporating theoretical perspectives from multiple disciplines to model processes underlying health-care satisfaction and (2) field testing those models before implementation. It also furthers research designed to provide health-care managers with actionable measures of the complex processes related to their clients' satisfaction.

Injury severity and disability in the selection of next level of care following acute medical treatment for traumatic brain injury.

PubMed

Malec, James F; Mandrekar, Jayawant N; Brown, Allen W; Moessner, Anne M

2009-01-01

To evaluate the association of demographic factors, post-traumatic amnesia (PTA) and a standardized measure of ability limitations with clinical decisions for Next Level of Care following acute hospital treatment for moderate-severe traumatic brain injury (TBI). A TBI Clinical Nurse specialist recorded PTA for 212 individuals and rated 159 on the Ability and Adjustment Indices of the Mayo-Portland Adaptability Inventory (MPAI-4) for comparison with clinical decisions. Multivariate logistic regression analyses revealed that independent ratings on the MPAI-4 Ability Index and PTA were associated with the clinical decision to admit to Inpatient Rehabilitation vs discharge to Home in 92.7% of the sample; ratings on the Ability Index alone were associated with this decision in 92.2% of cases. Age over 65 was the only variable associated with discharge to a Skilled Nursing Facility, correctly predicting this decision in 64% of cases. Use of a standardized measure of ability limitations appears feasible to provide supportive documentation and potentially improve the consistency of decision-making in recommending Inpatient Rehabilitation vs discharge to Home. Although age is a significant factor in the decision to discharge to a Skilled Nursing Facility, this decision appears complex and merits further study.

Comparison of Leishmania typing results obtained from 16 European clinical laboratories in 2014

PubMed Central

Van der Auwera, Gert; Bart, Aldert; Chicharro, Carmen; Cortes, Sofia; Davidsson, Leigh; Di Muccio, Trentina; Dujardin, Jean-Claude; Felger, Ingrid; Paglia, Maria Grazia; Grimm, Felix; Harms, Gundel; Jaffe, Charles L.; Manser, Monika; Ravel, Christophe; Robert-Gangneux, Florence; Roelfsema, Jeroen; Töz, Seray; Verweij, Jaco J.; Chiodini, Peter L.

2016-01-01

Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally. PMID:27983510

Influence of PAI-1 gene promoter-675 (4G/5G) polymorphism on fibrinolytic activity after cardiac surgery employing cardiopulmonary bypass.

PubMed

Ozolina, Agnese; Strike, Eva; Jaunalksne, Inta; Serova, Jelena; Romanova, Tatjana; Zake, Liene Nikitina; Sabelnikovs, Olegs; Vanags, Indulis

2012-01-01

The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

A study of the effect of dyad practice versus that of individual practice on simulation-based complex skills learning and of students' perceptions of how and why dyad practice contributes to learning.

PubMed

Räder, Sune B E W; Henriksen, Ann-Helen; Butrymovich, Vitalij; Sander, Mikael; Jørgensen, Erik; Lönn, Lars; Ringsted, Charlotte V

2014-09-01

The aims of this study were (1) to explore the effectiveness of dyad practice compared with individual practice on a simulator for learning a complex clinical skill and (2) to explore medical students' perceptions of how and why dyad practice on a simulator contributes to learning a complex skill. In 2011, the authors randomly assigned 84 medical students to either the dyad or the individual practice group to learn coronary angiography skills using instruction videos and a simulator. Two weeks later, participants each performed two video-recorded coronary angiographies on the simulator. Two raters used a rating scale to assess the participants' video-recorded performance. The authors then interviewed the participants in the dyad practice group. Seventy-two (86%) participants completed the study. The authors found no significant difference between the performance scores of the two groups (mean±standard deviation, 68%±13% for individual versus 63%±16% for dyad practice; P=.18). Dyad practice participants noted that several key factors contributed to their learning: being equal-level novices, the quality of the cooperation between partners, observational learning and overt communication, social aspects and motivation, and meta-cognition. Dyad practice is more efficient and thus more cost-effective than individual practice and can be used for costly virtual reality simulator training. However, dyad practice may not apply to clinical training involving real patients because learning from errors and overt communication, both keys to dyad practice, do not transfer to clinical practice.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Quantum therapy in correction of the lipidic metabolism at acute pancreatitis

NASA Astrophysics Data System (ADS)

Anaskin, S. G.; Vlasov, A. P.; Spirina, M. A.; Vlasova, T. I.; Muratova, T. A.; Korniletsky, I. D.; Geraskin, V. S.

2017-01-01

Attempt to establish efficiency of laser therapy in correction of a lipid metabolism at patients with acute pancreatitis was the purpose of work. There were clinical laboratory researches of 48 patients with acute heavy pancreatitis. To the first clinical group (comparison) standard therapy was carried out. To patients of the second clinical group (main) in addition to basic therapy within 10 days daily sessions of laser therapy by the device "Matrix" were held later. Radiation with the wavelength of 635 nanometers, 2 MW was used. Percutaneous laser radiation of blood was carried out to projections of a cubital vein within 30 minutes daily. Inclusion of laser therapy in complex treatment of patients with pancreatitis led to more significant positive dynamics. Reduction of weight of endotoxemia in the main group is set that was verified by decrease in level of both hydrophilic, and hydrophobic toxins. The analysis of the data obtained as a result of research in the main group revealed decrease in concentration of products of free radical oxidation of lipids in comparison with group of comparison for 12,1 - 17,3% of % (p. <. 0,05). Laser radiation of blood as a part of complex treatment led to reliable inhibition of activity of enzymes of phospholipase system in blood plasma, in particular activity of a phospholipase of A2 fell for 13,2 - 34,4% (p <0,05). Thus, inclusion of laser therapy in structure of complex treatment of sharp pancreatitis allowed to reduce significantly expressiveness of endogenous intoxication, intensity of processes of free radical oxidation of membrane lipids and activity of phospholipase systems.

The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies.

PubMed

Diana, Anna; Polizzi, Angela Maria; Santostasi, Teresa; Ratclif, Luigi; Pantaleo, Maria Giuseppina; Leonetti, Giuseppina; Iusco, Danila Rosa; Gallo, Crescenzio; Conese, Massimo; Manca, Antonio

2016-06-01

Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis.

Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

PubMed

Bruyère, Olivier; Cooper, Cyrus; Al-Daghri, Nasser M; Dennison, Elaine M; Rizzoli, René; Reginster, Jean-Yves

2018-02-01

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as "biosimilars" akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply.

Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis.

PubMed

Barrera, L; Montes-Servín, E; Barrera, A; Ramírez-Tirado, L A; Salinas-Parra, F; Bañales-Méndez, J L; Sandoval-Ríos, M; Arrieta, Ó

2015-02-01

Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases. Their effects are mediated through complex regulatory networks. Human cytokine profiles could define patient subgroups and represent new potential biomarkers. The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer (NSCLC). We conducted a prospective study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects. Cytokine levels and data-mining profiles were associated with clinical, quality of life and pathological outcomes. NSCLC patients had higher levels of interleukin (IL)-6, IL-8, IL-12p70, IL-17a and interferon (IFN)-γ, and lower levels of IL-33 and IL-29 compared with controls. The pro-inflammatory cytokines IL-1b, IL-6 and IL-8 were associated with lower hemoglobin levels, worse functional performance status (Eastern Cooperative Oncology Group, ECOG), fatigue and hyporexia. The anti-inflammatory cytokines IL-4, IL-10 and IL-33 were associated with anorexia and lower body mass index. We identified three clusters of patients according to data-mining analysis with different overall survival (OS; 25.4, 16.8 and 5.09 months, respectively, P = 0.0012). Multivariate analysis showed that ECOG performance status and data-mining clusters were significantly associated with OS (RR 3.59, [95% CI 1.9-6.7], P < 0.001 and 2.2, [1.2-3.8], P = 0.005). Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC. These cytokines may represent potential biomarkers, particularly in the immunotherapy era in cancer research. © The Author 2014. 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.

Physician styles of decision-making for a complex condition: Type 2 diabetes with co-morbid mental illness.

PubMed

Trachtenberg, Felicia L; Pober, David M; Welch, Lisa C; McKinlay, John B

Variation in physician decisions may reflect personal styles of decision-making, as opposed to singular clinical actions and these styles may be applied differently depending on patient complexity. The objective of this study is to examine clusters of physician decision-making for type 2 diabetes, overall and in the presence of a mental health co-morbidity. This randomized balanced factorial experiment presented video vignettes of a "patient" with diagnosed, but uncontrolled type 2 diabetes. "Patients" were systematically varied by age, sex, race and co-morbidity (depression, schizophrenia with normal or bizarre affect, eczema as control). Two hundred and fifty-six primary care physicians, balanced by gender and experience level, completed a structured interview about clinical management. Cluster analysis identified 3 styles of diabetes management. "Minimalists" (n=84) performed fewer exams or tests compared to "middle of the road" physicians (n=84). "Interventionists" (n=88) suggested more medications and referrals. A second cluster analysis, without control for co-morbidities, identified an additional cluster of "information seekers" (n=15) who requested more additional information and referrals. Physicians ranking schizophrenia higher than diabetes on their problem list were more likely "minimalists" and none were "interventionists" or "information seekers". Variations in clinical management encompass multiple clinical actions and physicians subtly shift these decision-making styles depending on patient co-morbidities. Physicians' practice styles may help explain persistent differences in patient care. Training and continuing education efforts to encourage physicians to implement evidence-based clinical practice should account for general styles of decision-making and for how physicians process complicating comorbidities.

Complex Meniscus Tears Treated with Collagen Matrix Wrapping and Bone Marrow Blood Injection

PubMed Central

Piontek, Tomasz; Ciemniewska-Gorzela, Kinga; Naczk, Jakub; Jakob, Roland; Szulc, Andrzej; Grygorowicz, Monika; Slomczykowski, Michal

2015-01-01

Objective To collect and analyze the 2-year follow-up clinical and MRI results of patients treated with an arthroscopic technique of collagen membrane-based meniscus repair. Design 53 consecutive patients with combined (horizontal and radial or longitudinal component) and complex meniscal tears (tear extended through avascular zones or/and composed with two or more morphological tear pattern) were treated with an “all-inside” arthroscopic suture of meniscus and wrapping with a collagen membrane (Chondro-Gide) technique with bone marrow blood injection. The IKDC 2000 subjective score, IKDC 2000 clinical evaluation score, Lysholm score and Barret clinical criteria of meniscal healing were recorded. All patients were examinated by MRI 2 years postoperatively, using modified WORMS criteria for meniscal integrity. Results The 2 year follow-up was achieved in 50 cases. Of these, 2 patients were excluded from the evaluation due to incomplete data and 2 patients underwent partial meniscectomy and were classified as failures. In 46 patients (86.8% of the intended to treat cases), a statistically significant improvement in IKDC 2000 subjective, Lysholm scores and IKDC 2000 clinical assessment between preoperative and the 2-year follow-up time points were obsereved. Barret criteria demonstrated an improved clinical outcome between pre- and post-operative values. MRI revealed a non-homogeneous signal without meniscal tear (WORMS grade 1) in 76% of the operated menisci (13% WORMS grade 2). Conclusions The 2-year follow-up data demonstrate that this technique is safe and can offer an additional tool to save the meniscus in the patients otherwise scheduled for meniscal removal. Level of evidence IV PMID:27047635

Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.

PubMed Central

Cohen, M G; Pollard, K M; Webb, J

1992-01-01

Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited. PMID:1540040

Amyotrophic lateral sclerosis: cell vulnerability or system vulnerability?

PubMed

Talbot, Kevin

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with clinical, pathological and genetic overlap with frontotemporal dementia (FTD). No longer viewed as one disease with a single unified cause, ALS is now considered to be a clinicopathological syndrome resulting from a complex convergence of genetic susceptibility, age-related loss of cellular homeostasis, and possible environmental influences. The rapid increase in recent years of the number of genes in which mutations have been associated with ALS has led to in vitro and in vivo models that have generated a wealth of data indicating disruption of specific biochemical pathways and sub-cellular compartments. Data implicating pathways including protein misfolding, mRNA splicing, oxidative stress, proteosome and mitochondrial dysfunction in the pathogenesis of ALS reinforce a disease model based on selective age-dependent vulnerability of a specific population of cells. To the clinical neurologist, however, ALS presents as a disease of focal onset and contiguous spread. Characteristic regional patterns of involvement and progression suggest that the disease does not proceed randomly but via a restricted number of anatomical pathways. These clinical observations combined with electrophysiological and brain-imaging studies underpin the concept of ALS at the macroscopic level as a 'system degeneration'. This dichotomy between cellular and systems neurobiology raises the fundamental questions of what initiates the disease process in a specific anatomical site and how the disease is propagated. Is the essence of ALS a cell-to-cell transmission of pathology with, for example, a 'prion-like' mechanism, or does the cellular pathology follow degeneration of specific synaptic networks? Elucidating the interaction between cellular degeneration and system level degeneration will aid modeling of the disease in the earliest phases, improve the development of sensitive markers of disease progression and response to therapy, and expand our understanding of the biological basis of clinical and pathological heterogeneity. © 2013 Anatomical Society.

Ready for practice? A study of confidence levels of final year dental students at Cardiff University and University College Cork.

PubMed

Honey, J; Lynch, C D; Burke, F M; Gilmour, A S M

2011-05-01

The aim of this study was to describe the self-reported confidence levels of final year students at the School of Dentistry, Cardiff University and at the University Dental School & Hospital, Cork, Ireland in performing a variety of dental procedures commonly completed in primary dental care settings. A questionnaire was distributed to 61 final year students at Cardiff and 34 final year students at Cork. Information requested related to the respondents confidence in performing a variety of routine clinical tasks, using a five-point scale (1=very little confidence, 5=very confident). Comparisons were made between the two schools, gender of the respondent, and whether or not a student intended completing a year of vocational training after graduation. A response rate of 74% was achieved (n=70). The greatest self-reported confidence scores were for 'scale and polish' (4.61), fissure sealants (4.54) and delivery of oral hygiene instruction (4.51). Areas with the least confidence were placement of stainless steel crowns (2.83), vital tooth bleaching (2.39) and surgical extractions (2.26). Students at Cardiff were more confident than those at Cork in performing simple extractions (Cardiff: 4.31; Cork: 3.76) and surgical extractions (Cardiff: 2.61; Cork: 1.88), whilst students in Cork were more confident in caries diagnosis (Cork: 4.24; Cardiff: 3.89) fissure sealing (Cork: 4.76; Cardiff: 4.33) and placement of preventive resin restorations (Cork: 4.68; Cardiff: 4.22).   Final year students at Cardiff and Cork were most confident in simpler procedures and procedures in which they had had most clinical experience. They were least confident in more complex procedures and procedures in which they had the least clinical experience. Increased clinical time in complex procedures may help in increasing final year students' confidence in those areas. © 2011 John Wiley & Sons A/S.

Clinical Problem Analysis (CPA): A Systematic Approach To Teaching Complex Medical Problem Solving.

ERIC Educational Resources Information Center

Custers, Eugene J. F. M.; Robbe, Peter F. De Vries; Stuyt, Paul M. J.

2000-01-01

Discusses clinical problem analysis (CPA) in medical education, an approach to solving complex clinical problems. Outlines the five step CPA model and examines the value of CPA's content-independent (methodical) approach. Argues that teaching students to use CPA will enable them to avoid common diagnostic reasoning errors and pitfalls. Compares…

Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder

PubMed Central

Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

2014-01-01

Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness. PMID:25733956

Complex care systems in developing countries: breast cancer patient navigation in Ethiopia.

PubMed

Dye, Timothy D; Bogale, Solomon; Hobden, Claire; Tilahun, Yared; Hechter, Vanessa; Deressa, Teshome; Bizé, Marion; Reeler, Anne

2010-02-01

As the global visibility and importance of breast cancer increases, especially in developing countries, ensuring that countries strengthen and develop health systems that support prevention, diagnosis, and treatment of a complex chronic disease is a priority. Understanding how breast cancer patients navigate health systems to reach appropriate levels of care is critical in assessing and improving the health system response in countries to an increasing breast cancer burden in their populations. Ethiopia has accelerated attention to breast cancer, expanding clinical and public health efforts at diagnosing and treating breast cancer earlier and more efficiently. This project used a mixed-method approach to assessing patient navigation of the healthcare system that resulted in care at the cancer referral hospital for Ethiopia (Tikur Anbessa Hospital [TAH]). In total, 69 patients representative of the entire breast cancer clinical population at TAH were interviewed. Navigation chains are widely divergent and typically involve 3 or more care nodes until they reach the referral hospital. Patients who consult traditional healers have significantly more care nodes to reach the referral hospital than others, and patients who have direct access to local and regional hospitals have the smallest number of care nodes. Patients report moving laterally from 1 health institution to another or regressing to lower levels of care, sometimes complicated by reinvolving traditional healers. The care system can be streamlined for breast cancer patients in Ethiopia to facilitate patient access to available and clinically effective diagnostic and treatment services in the country, largely through improving local primary care and hospital capacity to provide basic breast cancer services and improve detection and referral. Copyright 2009 American Cancer Society.

In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

PubMed Central

Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

2015-01-01

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

Translational Cognition for Decision Support in Critical Care Environments: A Review

PubMed Central

Patel, Vimla L.; Zhang, Jiajie; Yoskowitz, Nicole A.; Green, Robert; Sayan, Osman R.

2008-01-01

The dynamic and distributed work environment in critical care requires a high level of collaboration among clinical team members and a sophisticated task coordination system to deliver safe, timely and effective care. A complex cognitive system underlies the decision-making process in such cooperative workplaces. This methodological review paper addresses the issues of translating cognitive research to clinical practice with a specific focus on decision-making in critical care, and the role of information and communication technology to aid in such decisions. Examples are drawn from studies of critical care in our own research laboratories. Critical care, in this paper, includes both intensive (inpatient) and emergency (outpatient) care. We define translational cognition as the research on basic and applied cognitive issues that contribute to our understanding of how information is stored, retrieved and used for problem-solving and decision-making. The methods and findings are discussed in the context of constraints on decision-making in real world complex environments and implications for supporting the design and evaluation of decision support tools for critical care health providers. PMID:18343731

Translational cognition for decision support in critical care environments: a review.

PubMed

Patel, Vimla L; Zhang, Jiajie; Yoskowitz, Nicole A; Green, Robert; Sayan, Osman R

2008-06-01

The dynamic and distributed work environment in critical care requires a high level of collaboration among clinical team members and a sophisticated task coordination system to deliver safe, timely and effective care. A complex cognitive system underlies the decision-making process in such cooperative workplaces. This methodological review paper addresses the issues of translating cognitive research to clinical practice with a specific focus on decision-making in critical care, and the role of information and communication technology to aid in such decisions. Examples are drawn from studies of critical care in our own research laboratories. Critical care, in this paper, includes both intensive (inpatient) and emergency (outpatient) care. We define translational cognition as the research on basic and applied cognitive issues that contribute to our understanding of how information is stored, retrieved and used for problem-solving and decision-making. The methods and findings are discussed in the context of constraints on decision-making in real-world complex environments and implications for supporting the design and evaluation of decision support tools for critical care health providers.

Lentiviral diseases of sheep and goats: chronic pneumonia leukoencephalomyelitis and arthritis.

PubMed

Narayan, O; Cork, L C

1985-01-01

This review describes the pathogenesis of a slowly progressive disease complex caused by naturally occurring nononcogenic retroviruses in sheep and goats. In nature, infections are usually clinically silent, but disease may manifest itself after prolonged incubation periods. Clinically, this is seen as dyspnea, progressive paralysis, and/or progressive arthritis. In all organs the basic lesion is inflammatory with infiltration and proliferation of lymphocytes, plasma cells, and macrophages. Other organ-specific pathologic changes such as primary demyelination in the central nervous system and degeneration of cartilaginous structures in joints accompany inflammation. The viruses infect tissue-specific macrophage populations in vivo. Viral replication in these cells is restricted to minimal levels but continues indefinitely in the animal as a result of either failure to induce specific neutralizing antibodies or antigenic drift when neutralizing antibodies develop. Consistent low-grade viral replication sets the pace for disease by providing continuous antigenic stimulation for the inflammatory cellular immune response or antibodies that localize in the target tissues. These cells and immune complexes may have adverse effects on indigenous cell populations.

Value-Based Insurance Design Benefit Offsets Reductions In Medication Adherence Associated With Switch To Deductible Plan.

PubMed

Reed, Mary E; Warton, E Margaret; Kim, Eileen; Solomon, Matthew D; Karter, Andrew J

2017-03-01

Enrollment in high-deductible health plans is increasing out-of-pocket spending. But innovative plans that pair deductibles with value-based insurance designs can help preserve low-cost access to high-value treatments for patients by aligning coverage with clinical value. Among adults in high-deductible health plans who were prescribed medications for chronic conditions, we examined what impact a value-based pharmacy benefit that offered free chronic disease medications had on medication adherence. Overall, we found that the value-based plan offset reductions in medication adherence associated with switching to a deductible plan. The value-based plan appeared particularly beneficial for patients who started with low levels of medication adherence. Patients with additional clinical complexity or vulnerable populations living in neighborhoods with lower socioeconomic status, however, did not show adherence improvements and might not be taking advantage of value-based insurance design provisions. Additional efforts may be needed to educate patients about their nuanced benefit plans to help overcome initial confusion about these complex plans. Project HOPE—The People-to-People Health Foundation, Inc.

Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the Cryptococcus Genus

PubMed Central

Lumbsch, H. Thorsten; Bertout, Sebastien; Cabañes, F. Javier; Carbia, Mauricio; Chen, Min; Cuétara, Maria S.; Espinel-Ingroff, Ana; Falk, Rama; Ferrer Rodríguez, Consuelo; Fraser, James A.; Khan, Ziauddin; Kurtzman, Cletus P.; Lagrou, Katrien; Liao, Wanqing; Linares, Carlos; Nielsen, Kirsten; Pan, Weihua; Pekmezovic, Marina; Romeo, Orazio; Sánchez, Manuel; Sampaio, Ana; Sriburee, Pojana; Sugita, Takashi; Takashima, Masako; Taylor, John W.; Theelen, Bart; Tomazin, Rok; Verweij, Paul E.; Wahyuningsih, Retno

2017-01-01

ABSTRACT Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within C. neoformans were raised to species level, and the same was done for five genotypes within C. gattii. In a recent perspective (K. J. Kwon-Chung et al., mSphere 2:e00357-16, 2017, https://doi.org/10.1128/mSphere.00357-16), it was argued that this taxonomic proposal was premature and without consensus in the community. Although the authors of the perspective recognized the existence of genetic diversity, they preferred the use of the informal nomenclature “C. neoformans species complex” and “C. gattii species complex.” Here we highlight the advantage of recognizing these seven species, as ignoring these species will impede deciphering further biologically and clinically relevant differences between them, which may in turn delay future clinical advances. PMID:28875175

Examination of acetabular labral tear: a continued diagnostic challenge.

PubMed

Reiman, Michael P; Mather, Richard C; Hash, Thomas W; Cook, Chad E

2014-02-01

Acetabular labrum tears (ALT) are present in 22-55% of individuals with hip or groin pain. Tears can occur as a result of trauma or degeneration and are markedly associated with femoral acetabular morphological variations. An ALT can lead to biomechanical deficiencies and a loss of stability to the coxafemoral joint due to the labrum serving as a stabilising structure of this joint. The diagnosis of ALT is complex and multidimensional. Although tremendous improvements in diagnostic utility for ALT have occurred in the past 25 years, there are few patient history, clinical examination and special test findings that are unique to the condition. Imaging methods such as MRI, CT and ultrasonography have demonstrated reasonable accuracy, but not at a level that allows use as a stand-alone measure. Outcomes measures that focus on functional limitation or that are used to measure recovery should envelop the complexities of the condition and be captured using both self-report and physical performance measures. Only when patient history, objective testing, clinical examination special testing and imaging are combined can a clinician fully elucidate the multidimensional diagnosis of ALT.

Interpretation of biomonitoring data in clinical medicine and the exposure sciences

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

Williams, Bryan L.; Barr, Dana B.; Wright, J. Michael

2008-11-15

Biomonitoring has become a fundamental tool in both exposure science and clinical medicine. Despite significant analytical advances, the clinical use of environmental biomarkers remains in its infancy. Clinical use of environmental biomarkers poses some complex scientific and ethical challenges. The purpose of this paper is compare how the clinical and exposure sciences differ with respect to their interpretation and use of biological data. Additionally, the clinical use of environmental biomonitoring data is discussed. A case study is used to illustrate the complexities of conducting biomonitoring research on highly vulnerable populations in a clinical setting.

Registered nurses' clinical reasoning skills and reasoning process: A think-aloud study.

PubMed

Lee, JuHee; Lee, Young Joo; Bae, JuYeon; Seo, Minjeong

2016-11-01

As complex chronic diseases are increasing, nurses' prompt and accurate clinical reasoning skills are essential. However, little is known about the reasoning skills of registered nurses. This study aimed to determine how registered nurses use their clinical reasoning skills and to identify how the reasoning process proceeds in the complex clinical situation of hospital setting. A qualitative exploratory design was used with a think-aloud method. A total of 13 registered nurses (mean years of experience=11.4) participated in the study, solving an ill-structured clinical problem based on complex chronic patients cases in a hospital setting. Data were analyzed using deductive content analysis. Findings showed that the registered nurses used a variety of clinical reasoning skills. The most commonly used skill was 'checking accuracy and reliability.' The reasoning process of registered nurses covered assessment, analysis, diagnosis, planning/implementation, and evaluation phase. It is critical that registered nurses apply appropriate clinical reasoning skills in complex clinical practice. The main focus of registered nurses' reasoning in this study was assessing a patient's health problem, and their reasoning process was cyclic, rather than linear. There is a need for educational strategy development to enhance registered nurses' competency in determining appropriate interventions in a timely and accurate fashion. Copyright © 2016 Elsevier Ltd. All rights reserved.

The quality and readability of internet information regarding clavicle fractures.

PubMed

Zhang, Dafang; Schumacher, Charles; Harris, Mitchel Byron

2016-03-01

The internet has become a major source of health information for patients. However, there has been little scrutiny of health information available on the internet to the public. Our objectives were to evaluate the quality and readability of information available on the internet regarding clavicle fractures and whether they changed with academic affiliation of the website or with complexity of the search term. Through a prospective evaluation of 3 search engines using 3 different search terms of varying complexity ("broken collarbone," "collarbone fracture," and "clavicle fracture"), we evaluated 91 website hits for quality and readability. Websites were specifically analyzed by search term and by website type. Information quality was evaluated on a four-point scale, and information readability was assessed using the Flesch-Kincaid score for reading grade level. The average quality score for our website hits was low, and the average reading grade level was far above the recommended level. Academic websites offered significantly higher quality information, whereas commercial websites offered significantly lower quality information. The use of more complex search terms yielded information of higher reading grade level but not higher quality. Current internet information regarding clavicle fractures is of low quality and low readability. Higher quality information utilizing more accessible language on clavicle fractures is needed on the internet. It is important to be aware of the information accessible to patients prior to their presentation to our clinics. Patients should be advised to visit websites with academic affiliations and to avoid commercial websites. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Identification of Clinical Isolates of Mycobacteria with Gas-Liquid Chromatography Alone

PubMed Central

Tisdall, Philip A.; Roberts, Glenn D.; Anhalt, John P.

1979-01-01

Identification of 18 mycobacterial species was performed by analysis of profiles obtained by using gas-liquid chromatography. Organisms were saponified in methanolic NaOH, and the reaction mixture was treated with BF3 in methanol and extracted with a hexane-chloroform mixture. An identification scheme was developed from 128 stock strains and tested against a collection of 79 clinical isolates. By using gas-liquid chromatographic profiles alone, 58% of specimens were correctly identified to species level, and an additional 41% were correctly identified to a group of two or three organisms. Use in a clinical laboratory over a 2-month period proved chromatography to be as accurate as and more rapid than concurrent biochemical testing. Of 81 isolates tested, 64% were identified to species level by chromatography alone. An additional 35% were differentiated to the same groups of two or three organisms as found in our analysis of stock strains. These groups consisted of: Mycobacterium tuberculosis, M. bovis, and M. xenopi; M. avium complex, M. gastri, and M. scrofulaceum; or M. fortuitum and M. chelonei. Identification to species level from these groups could usually be done by colonial morphology alone and could always be done by the addition of one selected biochemical test. This study demonstrated the practical application of gas-liquid chromatography in the identification of mycobacteria in a clinical laboratory. In particular, all strains of M. gordonae and M. kansasii were identified to species level. M. tuberculosis was definitively identified in 85% of cases. When it could not be definitely identified, the only alternatives were M. bovis and M. xenopi, both of which are rare causes of infection. PMID:118984

Voltage-gated potassium channel-complex autoimmunity and associated clinical syndromes.

PubMed

Irani, Sarosh R; Vincent, Angela

2016-01-01

Voltage-gated potassium channel (VGKC)-complex antibodies are defined by the radioimmunoprecipitation of Kv1 potassium channel subunits from brain tissue extracts and were initially discovered in patients with peripheral nerve hyperexcitability (PNH). Subsequently, they were found in patients with PNH plus psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) with prominent amnesia and frequent seizures. Most recently, they have been described in patients with pure epilepsies, especially in patients with the novel and distinctive semiology termed faciobrachial dystonic seizures (FBDS). In each of these conditions, there is a close correlation between clinical measures and antibody levels. The VGKC-complex is a group of proteins that are strongly associated in situ and after extraction in mild detergent. Two major targets of the autoantibodies are leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). The patients with PNH or MoS are most likely to have CASPR2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. Crucially, each of these conditions has a good response to immunotherapies, often corticosteroids and plasma exchange, although optimal regimes require further study. VGKC-complex antibodies have also been described in neuropathic pain syndromes, chronic epilepsies, a polyradiculopathy in porcine abattoir workers, and some children with status epilepticus. Increasingly, however, the antigenic targets in these patients are not defined and in some cases the antibodies may be secondary rather than the primary cause. Future serologic studies should define all the antigenic components of the VGKC-complex, and further inform mechanisms of antibody pathogenicity and related inflammation. © 2016 Elsevier B.V. All rights reserved.

Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study.

PubMed

Cheishvili, David; Maayan, Channa; Holzer, Naama; Tsenter, Jeanna; Lax, Elad; Petropoulos, Sophie; Razin, Aharon

2016-07-01

Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy, primarily presented in Ashkenazi Jews. The most common mutation in FD patients results from a single base pair substitution of an intronic splice site in the IKBKAP gene which disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP). To date, treatment of FD patients remains preventative, symptomatic and supportive. Based on previous in vitro evidence that tocotrienols, members of the vitamin E family, upregulate transcription of the IKBKAP gene, we aimed to investigate whether a similar effects was observed in vivo. In the current study, we assessed the effects of tocotrienol treatment on FD patients' symptoms and IKBKAP expression in white blood cells. The initial daily doses of 50 or 100 mg tocotrienol, doubled after 3 months, was administered to 32 FD patients. Twenty-eight FD patients completed the 6-month study. The first 3 months of tocotrienol treatment was associated with a significant increase in IKBKAP expression level in FD patients' blood. Despite doubling the dose after the initial 3 months of treatment, IKBKAP expression level returned to baseline by the end of the 6-month treatment. Clinical improvement was noted in the reported clinical questionnaire (with regard to dizziness, bloching, sweating, number of pneumonia, cough episodes, and walking stability), however, no significant effect was observed in any clinical measurements (weight, height, oxygen saturation, blood pressure, tear production, histamine test, vibration threshold test, nerve conduction, and heart rate variability) following Tocotrienol treatment. In conclusion, tocotrienol treatment appears significantly beneficial by clinical evaluation for some FD patients in a few clinical parameters; however it was not significant by clinical measurements. This open-label study shows the complexity of effect of tocotrienol treatment on FD patients' clinical outcomes and on IKBKAP expression level compared to in vitro results. A longitudinal study with an increased sample size is required in the future to better understand tocotrienol affect on FD patients.

With nurse practitioners, who needs house officers?

PubMed Central

Dowling, S.; Barrett, S.; West, R.

1995-01-01

The boundaries between the work of doctors and that of nurses are changing, with nurses taking over important parts of junior hospital doctors' clinical work. In 1993 an exploratory study was carried out to identify the professional, educational, and management issues that such developments raise. Interviews were carried out with a range of stakeholders in three innovatory posts in which nurses were doing much of the clinical work of house officers. A complex picture of perceived benefits and problems for patients, junior doctors, and nurses emerged. These seemed to be associated with (a) the extent to which the contribution of professional nursing was valued in the new role and (b) the amount of clinical discretion which the postholder was allowed, this depending on the type of preparatory education provided and the management of the post. The study points to the need for strategic issues--such as the development of appropriate education and the professional recognition of these new clinical roles--to be addressed at a national and regional level. Images p312-a PMID:7633246

Case Mis-Conceptualization in Psychological Treatment: An Enduring Clinical Problem.

PubMed

Ridley, Charles R; Jeffrey, Christina E; Roberson, Richard B

2017-04-01

Case conceptualization, an integral component of mental health treatment, aims to facilitate therapeutic gains by formulating a clear picture of a client's psychological presentation. However, despite numerous attempts to improve this clinical activity, it remains unclear how well existing methods achieve their purported purpose. Case formulation is inconsistently defined in the literature and implemented in practice, with many methods varying in complexity, theoretical grounding, and empirical support. In addition, many of the methods demand a precise clinical acumen that is easily influenced by judgmental and inferential errors. These errors occur regardless of clinicians' level of training or amount of clinical experience. Overall, the lack of a consensus definition, a diversity of methods, and susceptibility of clinicians to errors are manifestations of the state of crisis in case conceptualization. This article, the 2nd in a series of 5 on thematic mapping, argues the need for more reliable and valid models of case conceptualization. © 2017 Wiley Periodicals, Inc.

PHEOCHROMOCYTOMA: IMPLICATIONS IN TUMORIGENESIS AND THE ACTUAL MANAGEMENT

PubMed Central

Shah, Urvi; Giubellino, Alessio; Pacak, Karel

2012-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and has been discussed along with advances in its treatment. PMID:22691888

Pheochromocytoma: implications in tumorigenesis and the actual management.

PubMed

Shah, U; Giubellino, A; Pacak, K

2012-06-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.

Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

PubMed

Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

2017-12-01

Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

PubMed

Louridas, George E; Lourida, Katerina G

2017-02-21

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

Exercise prescription for overhead athletes with shoulder pathology: a systematic review with best evidence synthesis.

PubMed

Wright, Alexis A; Hegedus, Eric J; Tarara, Daniel T; Ray, Samantha C; Dischiavi, Steven L

2018-02-01

To produce a best evidence synthesis of exercise prescription used when treating shoulder pathology in the overhead athlete. A systematic review of exercises used in overhead athletes including case studies and clinical commentaries. MEDLINE, PubMed, SPORTDiscus and CINAHL from database inception through July 8, 2016. We examined data from randomised controlled trials and prospective cohort (level I-IV evidence) studies that addressed exercise intervention in the rehabilitation of the overhead athlete with shoulder pathology. Case studies and clinical commentaries (level V evidence) were examined to account for expert opinion-based research. Data were combined using best evidence synthesis and graded (A-F) recommendations (Centre for Evidence-Based Medicine). There were 33 unique exercises in six level I-IV studies that met our inclusion criteria. Most exercises were single-plane, upper extremity exercises performed below 90 o of elevation. There were 102 unique exercises in 33 level V studies that met our inclusion criteria. These exercises emphasised plyometrics, kinetic chain and sport-specific training. Overall, evidence for exercise interventions in overhead athletes with shoulder pathology is dominated by expert opinion (grade D). There is great variability between exercise approaches suggested by experts and those investigated in research studies and the overall level of evidence is low. The strongest available evidence (level B) supports the use of single-plane, open chain upper extremity exercises performed below 90° of elevation and closed chain upper extremity exercises. Clinical expert pieces support a more advanced, global treatment approach consistent with the complex, multidimensional nature of sport. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Qualitative and quantitative descriptions of glenohumeral motion.

PubMed

Hill, A M; Bull, A M J; Wallace, A L; Johnson, G R

2008-02-01

Joint modelling plays an important role in qualitative and quantitative descriptions of both normal and abnormal joints, as well as predicting outcomes of alterations to joints in orthopaedic practice and research. Contemporary efforts in modelling have focussed upon the major articulations of the lower limb. Well-constrained arthrokinematics can form the basis of manageable kinetic and dynamic mathematical predictions. In order to contain computation of shoulder complex modelling, glenohumeral joint representations in both limited and complete shoulder girdle models have undergone a generic simplification. As such, glenohumeral joint models are often based upon kinematic descriptions of inadequate degrees of freedom (DOF) for clinical purposes and applications. Qualitative descriptions of glenohumeral motion range from the parody of a hinge joint to the complex realism of a spatial joint. In developing a model, a clear idea of intention is required in order to achieve a required application. Clinical applicability of a model requires both descriptive and predictive output potentials, and as such, a high level of validation is required. Without sufficient appreciation of the clinical intention of the arthrokinematic foundation to a model, error is all too easily introduced. Mathematical description of joint motion serves to quantify all relevant clinical parameters. Commonly, both the Euler angle and helical (screw) axis methods have been applied to the glenohumeral joint, although concordance between these methods and classical anatomical appreciation of joint motion is limited, resulting in miscommunication between clinician and engineer. Compounding these inconsistencies in motion quantification is gimbal lock and sequence dependency.

Methods to Succeed in Effective Knowledge Translation in Clinical Practice.

PubMed

Kitson, Alison L; Harvey, Gillian

2016-05-01

To explore the evidence around facilitation as an intervention for the successful implementation of new knowledge into clinical practice. The revised version of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, called the integrated or i-PARIHS framework, is used as the explanatory framework. This framework posits that evidence is a multidimensional construct embedded within innovation and operationalized by clinicians (individuals and within teams), working across multiple layers of context. Facilitation is the active ingredient that promotes successful implementation. An emerging body of evidence supports facilitation as a mechanism to getting new knowledge into clinical practice. Facilitation roles are divided into beginner, experienced, and expert facilitators. Facilitators can be internal or external to the organization they work in, and their skills and attributes complement other knowledge translation (KT) roles. Complex KT projects require facilitators who are experienced in implementation methods. Facilitation is positioned as the active ingredient to effectively introduce new knowledge into a clinical setting. Levels of facilitation experience are assessed in relation to the complexity of the KT task. Three core facilitation roles are identified, and structured interventions are established taking into account the nature and novelty of the evidence, the receptiveness of the clinicians, and the context or setting where the new evidence is to be introduced. Roles such as novice, experienced, and expert facilitators have important and complementary parts to play in enabling the successful translation of evidence into everyday practice in order to provide effective care for patients. © 2016 Sigma Theta Tau International.

Ethical Considerations in Tissue Engineering Research: Case Studies in Translation

PubMed Central

Baker, Hannah B.; McQuilling, John P.

2016-01-01

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of “modest translational distance” and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. PMID:26282436

Ethical considerations in tissue engineering research: Case studies in translation.

PubMed

Baker, Hannah B; McQuilling, John P; King, Nancy M P

2016-04-15

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. Copyright © 2015 Elsevier Inc. All rights reserved.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITYEXECUTIVE SUMMARYComplete Guidelines available at https://www.aace.com/publications/guidelines.

PubMed

Garvey, W Timothy; Mechanick, Jeffrey I; Brett, Elise M; Garber, Alan J; Hurley, Daniel L; Jastreboff, Ania M; Nadolsky, Karl; Pessah-Pollack, Rachel; Plodkowski, Raymond

2016-07-01

Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors. There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A], 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,788 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 351 (19.6%) based on reviews and opinions (EL 4). The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety. A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology AMA = American Medical Association BEL = best evidence level BMI = body mass index CCO = Consensus Conference on Obesity CPG = clinical practice guideline CSS = cross-sectional study CVD = cardiovascular disease EL = evidence level FDA = Food and Drug Administration GERD = gastroesophageal reflux disease HDL-c = high-density lipoprotein cholesterol IFG = impaired fasting glucose IGT = impaired glucose tolerance LDL-c = low-density lipoprotein cholesterol MNRCT = meta-analysis of non-randomized prospective or case-controlled trials NE = no evidence PCOS = polycystic ovary syndrome RCT = randomized controlled trial SS = surveillance study U.S = United States.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and accurate identification of Pseudallescheria/Scedosporium species.

PubMed

Sitterlé, E; Giraud, S; Leto, J; Bouchara, J P; Rougeron, A; Morio, F; Dauphin, B; Angebault, C; Quesne, G; Beretti, J L; Hassouni, N; Nassif, X; Bougnoux, M E

2014-09-01

An increasing number of infections due to Pseudallescheria/Scedosporium species has been reported during the past decades, both in immunocompromised and immunocompetent patients. Additionally, these fungi are now recognized worldwide as common agents of fungal colonization of the airways in cystic fibrosis patients, which represents a risk factor for disseminated infections after lung transplantation. Currently six species are described within the Pseudallescheria/Scedosporium genus, including Scedosporium prolificans and species of the Pseudallescheria/Scedosporium apiospermum complex (i.e. S. apiospermum sensu stricto, Pseudallescheria boydii, Scedosporium aurantiacum, Pseudallescheria minutispora and Scedosporium dehoogii). Precise identification of clinical isolates at the species level is required because these species differ in their antifungal drug susceptibility patterns. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/mass spectrometry (MS) is a powerful tool to rapidly identify moulds at the species level. We investigated the potential of this technology to discriminate Pseudallescheria/Scedosporium species. Forty-seven reference strains were used to build a reference database library. Profiles from 3-, 5- and 7-day-old cultures of each reference strain were analysed to identify species-specific discriminating profiles. The database was tested for accuracy using a set of 64 clinical or environmental isolates previously identified by multilocus sequencing. All isolates were unequivocally identified at the species level by MALDI-TOF/MS. Our results, obtained using a simple protocol, without prior protein extraction or standardization of the culture, demonstrate that MALDI-TOF/MS is a powerful tool for rapid identification of Pseudallescheria/Scedosporium species that cannot be currently identified by morphological examination in the clinical setting. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Evidence-based decision-making as a practice-based learning skill: a pilot study.

PubMed

Falzer, Paul R; Garman, D Melissa

2012-03-01

As physicians are being trained to adapt their practices to the needs and experience of patients, initiatives to standardize care have been gaining momentum. The resulting conflict can be addressed through a practice-based learning and improvement (PBL) program that develops competency in using treatment guidelines as decision aids and incorporating patient-specific information into treatment recommendations. This article describes and tests a program that is consistent with the ACGME's multilevel competency-based approach, targets students at four levels of training, and features progressive learning objectives and assessments. The program was pilot-tested with 22 paid volunteer psychiatric residents and fellows. They were introduced to a schizophrenia treatment guideline and reviewed six case vignettes of varying complexity. PBL assessments were based on how treatment recommendations were influenced by clinical and patient-specific factors. The task permitted separate assessments of learning objectives all four training levels. Among the key findings at each level, most participants found the treatment guideline helpful in making treatment decisions. Recommendations were influenced by guideline-based assessment criteria and other clinical features. They were also influenced by patients' perceptions of their illness, patient-based progress assessments, and complications such as stressors and coping patterns. Recommendations were strongly influenced by incongruence between clinical facts and patient experience. Practical understanding of how patient experience joins with clinical knowledge can enhance the use of treatment guidelines as decision tools and enable clinicians to appreciate more fully how and why patients' perceptions of their illness should influence treatment recommendations. This PBL program can assist training facilities in preparing students to cope with contradictory demands to both standardize and adapt their practice. The program can be modified to accommodate various disorders and a range of clinical factors and patient-specific complications.

A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

PubMed

Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

2017-01-01

All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

Factors that predispose, prime and precipitate NREM parasomnias in adults: clinical and forensic implications.

PubMed

Pressman, Mark R

2007-02-01

Sleepwalking and related disorders are the result of factors that predispose, prime and precipitate episodes. In the absence of one or more of these factors sleepwalking is unlikely to occur. Predisposition to sleepwalking is based on genetic susceptibility and has a familial pattern. Priming factors include conditions and substances that increase slow wave sleep (SWS) or make arousal from sleep more difficult. These factors include sleep deprivation, alcohol, medications, situational stress and fever among others. The patient with a genetic predisposition to sleepwalking and with priming factors still requires a precipitating factor or trigger to set the sleepwalking episode in motion. Classical theories of sleepwalking were based primarily on case reports. Recently some of these theories have been tested in the sleep laboratory. Experimental sleep deprivation studies of sleepwalkers generally report an increase in complex behaviors during SWS, although one prominent study reported the opposite effect. However, the generally accepted theory that alcohol and medications can induce sleepwalking episodes remains entirely based on clinical and forensic case reports. Alleged cases of alcohol related sleepwalking often involve individuals lacking the generally accepted characteristics of sleepwalkers but with very high blood alcohol levels that could in and of itself account for complex behaviors noted without the presence of sleepwalking. Further, the effects of high levels of alcohol dramatically decrease SWS, a finding inconsistent with sleepwalking. Case reports of medication-related induction of apparent sleepwalking most often present a complex medical and psychiatric history associated with multiple medications. These patients often lack the clinical history and other criteria currently required for the diagnosis of sleepwalking. The medication-related behaviors may instead represent some other condition in an awake, but impaired patient. Sleep laboratory research has identified sleep disordered breathing, periodic leg movements, noise and touch among others as proximal triggers of sleepwalking episodes. Treatment of these triggers may result in resolution of sleepwalking without medication. Further sleep laboratory research is needed before experimental findings can be used for routine diagnostic and forensic purposes.

Lipoprotein (a): impact by ethnicity and environmental and medical conditions

PubMed Central

Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

2016-01-01

Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases. PMID:26637279

Visually defining and querying consistent multi-granular clinical temporal abstractions.

PubMed

Combi, Carlo; Oliboni, Barbara

2012-02-01

The main goal of this work is to propose a framework for the visual specification and query of consistent multi-granular clinical temporal abstractions. We focus on the issue of querying patient clinical information by visually defining and composing temporal abstractions, i.e., high level patterns derived from several time-stamped raw data. In particular, we focus on the visual specification of consistent temporal abstractions with different granularities and on the visual composition of different temporal abstractions for querying clinical databases. Temporal abstractions on clinical data provide a concise and high-level description of temporal raw data, and a suitable way to support decision making. Granularities define partitions on the time line and allow one to represent time and, thus, temporal clinical information at different levels of detail, according to the requirements coming from the represented clinical domain. The visual representation of temporal information has been considered since several years in clinical domains. Proposed visualization techniques must be easy and quick to understand, and could benefit from visual metaphors that do not lead to ambiguous interpretations. Recently, physical metaphors such as strips, springs, weights, and wires have been proposed and evaluated on clinical users for the specification of temporal clinical abstractions. Visual approaches to boolean queries have been considered in the last years and confirmed that the visual support to the specification of complex boolean queries is both an important and difficult research topic. We propose and describe a visual language for the definition of temporal abstractions based on a set of intuitive metaphors (striped wall, plastered wall, brick wall), allowing the clinician to use different granularities. A new algorithm, underlying the visual language, allows the physician to specify only consistent abstractions, i.e., abstractions not containing contradictory conditions on the component abstractions. Moreover, we propose a visual query language where different temporal abstractions can be composed to build complex queries: temporal abstractions are visually connected through the usual logical connectives AND, OR, and NOT. The proposed visual language allows one to simply define temporal abstractions by using intuitive metaphors, and to specify temporal intervals related to abstractions by using different temporal granularities. The physician can interact with the designed and implemented tool by point-and-click selections, and can visually compose queries involving several temporal abstractions. The evaluation of the proposed granularity-related metaphors consisted in two parts: (i) solving 30 interpretation exercises by choosing the correct interpretation of a given screenshot representing a possible scenario, and (ii) solving a complex exercise, by visually specifying through the interface a scenario described only in natural language. The exercises were done by 13 subjects. The percentage of correct answers to the interpretation exercises were slightly different with respect to the considered metaphors (54.4--striped wall, 73.3--plastered wall, 61--brick wall, and 61--no wall), but post hoc statistical analysis on means confirmed that differences were not statistically significant. The result of the user's satisfaction questionnaire related to the evaluation of the proposed granularity-related metaphors ratified that there are no preferences for one of them. The evaluation of the proposed logical notation consisted in two parts: (i) solving five interpretation exercises provided by a screenshot representing a possible scenario and by three different possible interpretations, of which only one was correct, and (ii) solving five exercises, by visually defining through the interface a scenario described only in natural language. Exercises had an increasing difficulty. The evaluation involved a total of 31 subjects. Results related to this evaluation phase confirmed us about the soundness of the proposed solution even in comparison with a well known proposal based on a tabular query form (the only significant difference is that our proposal requires more time for the training phase: 21 min versus 14 min). In this work we have considered the issue of visually composing and querying temporal clinical patient data. In this context we have proposed a visual framework for the specification of consistent temporal abstractions with different granularities and for the visual composition of different temporal abstractions to build (possibly) complex queries on clinical databases. A new algorithm has been proposed to check the consistency of the specified granular abstraction. From the evaluation of the proposed metaphors and interfaces and from the comparison of the visual query language with a well known visual method for boolean queries, the soundness of the overall system has been confirmed; moreover, pros and cons and possible improvements emerged from the comparison of different visual metaphors and solutions. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimization of protocol design: a path to efficient, lower cost clinical trial execution

PubMed Central

Malikova, Marina A

2016-01-01

Managing clinical trials requires strategic planning and efficient execution. In order to achieve a timely delivery of important clinical trials’ outcomes, it is useful to establish standardized trial management guidelines and develop robust scoring methodology for evaluation of study protocol complexity. This review will explore the challenges clinical teams face in developing protocols to ensure that the right patients are enrolled and the right data are collected to demonstrate that a drug is safe and efficacious, while managing study costs and study complexity based on proposed comprehensive scoring model. Key factors to consider when developing protocols and techniques to minimize complexity will be discussed. A methodology to identify processes at planning phase, approaches to increase fiscal return and mitigate fiscal compliance risk for clinical trials will be addressed. PMID:28031939

Modeling Complex Workflow in Molecular Diagnostics

PubMed Central

Gomah, Mohamed E.; Turley, James P.; Lu, Huimin; Jones, Dan

2010-01-01

One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency. PMID:20007844

Cationic Lipid-Nucleic Acid Complexes for Gene Delivery And Silencing: Pathways And Mechanisms for Plasmid Dna And Sirna

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

Ewert, K.K.; Zidovska, A.; Ahmad, A.

2012-07-17

Motivated by the promises of gene therapy, there is great interest in developing non-viral lipid-based vectors for therapeutic applications due to their low immunogenicity, low toxicity, ease of production, and the potential of transferring large pieces of DNA into cells. In fact, cationic liposome (CL) based vectors are among the prevalent synthetic carriers of nucleic acids (NAs) currently used in gene therapy clinical trials worldwide. These vectors are studied both for gene delivery with CL-DNA complexes and gene silencing with CL-siRNA (short interfering RNA) complexes. However, their transfection efficiencies and silencing efficiencies remain low compared to those of engineered viralmore » vectors. This reflects the currently poor understanding of transfection-related mechanisms at the molecular and self-assembled levels, including a lack of knowledge about interactions between membranes and double stranded NAs and between CL-NA complexes and cellular components. In this review we describe our recent efforts to improve the mechanistic understanding of transfection by CL-NA complexes, which will help to design optimal lipid-based carriers of DNA and siRNA for therapeutic gene delivery and gene silencing.« less

High conservation of herpes simplex virus UL5/UL52 helicase-primase complex in the era of new antiviral therapies.

PubMed

Collot, Marianne; Rouard, Caroline; Brunet, Christel; Agut, Henri; Boutolleau, David; Burrel, Sonia

2016-04-01

The emergence of herpes simplex virus (HSV) resistance to current antiviral drugs, that all target the viral DNA polymerase, constitutes a major obstacle to antiviral treatment effectiveness of HSV infections, especially in immunocompromised patients. A novel and promising class of inhibitors of the HSV UL5/UL52 helicase-primase (HP) complex has been reported to hinder viral replication with a high potency. In this study, we describe the low natural polymorphism (interstrain identity >99.1% at both nucleotide and amino acid levels) of HSV HP complex subunits pUL5 and pUL52 among 64 HSV (32 HSV-1 and 32 HSV-2) clinical isolates, and we show that the HSV resistance profile to the first-line antiviral drug acyclovir (ACV) does not impact on the natural polymorphism of HSV HP complex. Genotypic tools and polymorphism data concerning HSV HP complex provided herein will be useful to detect drug resistance mutations in a relevant time frame when HP inhibitors (HPIs), i.e., amenamevir and pritelivir, will be available in medical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of the Communication Complexity Scale

PubMed Central

Brady, Nancy C.; Fleming, Kandace; Thiemann-Bourque, Kathy; Olswang, Lesley; Dowden, Patricia; Saunders, Muriel D.

2011-01-01

Accurate description of an individual's communication status is critical in both research and practice. Describing the communication status of individuals with severe intellectual and developmental disabilities is difficult because these individuals often communicate with presymbolic means that may not be readily recognized. Our goal was to design a communication scale and summary score for interpretation that could be applied across populations of children and adults with limited (often presymbolic) communication forms. Methods The Communication Complexity Scale (CCS) was developed by a team of researchers and tested with 178 participants with varying levels of presymbolic and early symbolic communication skills. Correlations between standardized and informant measures were completed, and expert opinions were obtained regarding the CCS. Results CCS scores were within expected ranges for the populations studied and inter-rater reliability was high. Comparison across other measures indicated significant correlations with standardized tests of language. Scores on informant report measures tended to place children at higher levels of communication. Expert opinions generally favored the development of the CCS. Clinical implications The scale appears to be useful for describing a given individual's level of presymbolic or early symbolic communication. Further research is needed to determine if it is sensitive to developmental growth in communication. PMID:22049404

The elementome of calcium-based urinary stones and its role in urolithiasis

PubMed Central

Ramaswamy, Krishna; Killilea, David W.; Kapahi, Pankaj; Kahn, Arnold J.; Chi, Thomas; Stoller, Marshall L.

2016-01-01

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components. Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective. Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity. The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns. Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation. The elementome—the full spectrum of elemental content—of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease. PMID:26334088

[Antiseptic sensitivity of clinical strains of Pseudomonas aeruginosa].

PubMed

Adarchenko, A A; Krasil'nikov, A P; Sobeshchuk, O P

1989-12-01

MICs, the frequency of clinical and statistic resistance and the antiseptic activity index were studied in complex on out-of-hospital and hospital ecovars of P. aeruginosa. The forms resistant to a number of antiseptics, i.e. chloramine B, chlorhexidine, decamethoxine and dioxidine whose frequency eventually increased were shown to be widely distributed. The antiseptic sensitivity spectrum was more narrow and more heterogeneous than that of other bacteria, the heterogeneity level being dependent on the antiseptic type and bacterial ecovar. The activity of pervomur, phenol, resorcin and boric acid was higher against the clinical strains of P. aeruginosa while iodopyrin, sulfacetamide sodium and dioxidine were less active. The P. aeruginosa strains had natural resistance to cetylpyridinium chloride, rokkal, ethonium, sodium laurate and laurylsulfate and rivanol. It was recommended to assay antiseptic sensitivity of agents causing purulent inflammatory infections and to control circulation of antiseptic resistant variants of bacteria in hospitals.

[Public health, genetics and ethics].

PubMed

Kottow, Miguel H

2002-10-01

Genetics research has shown enormous developments in recent decades, although as yet with only limited clinical application. Bioethical analysis has been unable to deal with the vast problems of genetics because emphasis has been put on the principlism applied to both clinical and research bioethics. Genetics nevertheless poses its most complex moral dilemmas at the public level, where a social brand of ethics ought to supersede the essentially interpersonal perspective of principlism. A more social understanding of ethics in genetics is required to unravel issues such as research and clinical explorations, ownership and patents, genetic manipulation, and allocation of resources. All these issues require reflection based on the requirements of citizenry, consideration of common assets, and definition of public policies in regulating genetic endeavors and protecting the society as a whole Bioethics has privileged the approach to individual ethical issues derived from genetic intervention, thereby neglecting the more salient aspects of genetics and social ethics.

The orthodontic-periodontic interrelationship in integrated treatment challenges: a systematic review.

PubMed

Gkantidis, N; Christou, P; Topouzelis, N

2010-05-01

Orthodontic treatment aims at providing an acceptable functional and aesthetic occlusion with appropriate tooth movements. These movements are strongly related to interactions of teeth with their supportive periodontal tissues. In recent years, because of the increased number of adult patients seeking orthodontic treatment, orthodontists frequently face patients with periodontal problems. Aesthetic considerations, like uneven gingival margins or functional problems resulting from inflammatory periodontal diseases should be considered in orthodontic treatment planning. Furthermore, in cases with severe periodontitis, orthodontics may improve the possibilities of saving and restoring a deteriorated dentition. In modern clinical practice, the contribution of the orthodontist, the periodontist and the general dentist is essential for optimized treatment outcomes. The purpose of this systematic review is to highlight the relationship between orthodontics and periodontics in clinical practice and to improve the level of cooperation between dental practitioners. Potentials and limitations that derive from the interdisciplinary approach of complex orthodontic-periodontal clinical problems are discussed.

Factors Associated With Having a Physician, Nurse Practitioner, or Physician Assistant as Primary Care Provider for Veterans With Diabetes Mellitus

PubMed Central

Morgan, Perri; Everett, Christine M.; Smith, Valerie A.; Woolson, Sandra; Edelman, David; Hendrix, Cristina C.; Berkowitz, Theodore S. Z.; White, Brandolyn; Jackson, George L.

2017-01-01

Expanded use of nurse practitioners (NPs) and physician assistants (PAs) is a potential solution to workforce issues, but little is known about how NPs and PAs can best be used. Our study examines whether medical and social complexity of patients is associated with whether their primary care provider (PCP) type is a physician, NP, or PA. In this national retrospective cohort study, we use 2012-2013 national Veterans Administration (VA) electronic health record data from 374 223 veterans to examine whether PCP type is associated with patient, clinic, and state-level factors representing medical and social complexity, adjusting for all variables simultaneously using a generalized logit model. Results indicate that patients with physician PCPs are modestly more medically complex than those with NP or PA PCPs. For the group having a Diagnostic Cost Group (DCG) score >2.0 compared with the group having DCG <0.5, odds of having an NP or a PA were lower than for having a physician PCP (NP odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.79-0.88; PA OR = 0.85, CI: 0.80-0.89). Social complexity is not consistently associated with PCP type. Overall, we found minor differences in provider type assignment. This study improves on previous work by using a large national dataset that accurately ascribes the work of NPs and PAs, analyzing at the patient level, analyzing NPs and PAs separately, and addressing social as well as medical complexity. This is a requisite step toward studies that compare patient outcomes by provider type. PMID:28617196

Factors Associated With Having a Physician, Nurse Practitioner, or Physician Assistant as Primary Care Provider for Veterans With Diabetes Mellitus.

PubMed

Morgan, Perri; Everett, Christine M; Smith, Valerie A; Woolson, Sandra; Edelman, David; Hendrix, Cristina C; Berkowitz, Theodore S Z; White, Brandolyn; Jackson, George L

2017-01-01

Expanded use of nurse practitioners (NPs) and physician assistants (PAs) is a potential solution to workforce issues, but little is known about how NPs and PAs can best be used. Our study examines whether medical and social complexity of patients is associated with whether their primary care provider (PCP) type is a physician, NP, or PA. In this national retrospective cohort study, we use 2012-2013 national Veterans Administration (VA) electronic health record data from 374 223 veterans to examine whether PCP type is associated with patient, clinic, and state-level factors representing medical and social complexity, adjusting for all variables simultaneously using a generalized logit model. Results indicate that patients with physician PCPs are modestly more medically complex than those with NP or PA PCPs. For the group having a Diagnostic Cost Group (DCG) score >2.0 compared with the group having DCG <0.5, odds of having an NP or a PA were lower than for having a physician PCP (NP odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.79-0.88; PA OR = 0.85, CI: 0.80-0.89). Social complexity is not consistently associated with PCP type. Overall, we found minor differences in provider type assignment. This study improves on previous work by using a large national dataset that accurately ascribes the work of NPs and PAs, analyzing at the patient level, analyzing NPs and PAs separately, and addressing social as well as medical complexity. This is a requisite step toward studies that compare patient outcomes by provider type.

Characterization of a Multi-element Clinical HIFU System Using Acoustic Holography and Nonlinear Modeling

PubMed Central

Kreider, Wayne; Yuldashev, Petr V.; Sapozhnikov, Oleg A.; Farr, Navid; Partanen, Ari; Bailey, Michael R.; Khokhlova, Vera A.

2014-01-01

High-intensity focused ultrasound (HIFU) is a treatment modality that relies on the delivery of acoustic energy to remote tissue sites to induce thermal and/or mechanical tissue ablation. To ensure the safety and efficacy of this medical technology, standard approaches are needed for accurately characterizing the acoustic pressures generated by clinical ultrasound sources under operating conditions. Characterization of HIFU fields is complicated by nonlinear wave propagation and the complexity of phased-array transducers. Previous work has described aspects of an approach that combines measurements and modeling, and here we demonstrate this approach for a clinical phased array transducer. First, low-amplitude hydrophone measurements were performed in water over a scan plane between the array and the focus. Second, these measurements were used to holographically reconstruct the surface vibrations of the transducer and to set a boundary condition for a 3-D acoustic propagation model. Finally, nonlinear simulations of the acoustic field were carried out over a range of source power levels. Simulation results were compared to pressure waveforms measured directly by hydrophone at both low and high power levels, demonstrating that details of the acoustic field including shock formation are quantitatively predicted. PMID:25004539

In vivo behavior of NTBI revealed by automated quantification system.

PubMed

Ito, Satoshi; Ikuta, Katsuya; Kato, Daisuke; Lynda, Addo; Shibusa, Kotoe; Niizeki, Noriyasu; Toki, Yasumichi; Hatayama, Mayumi; Yamamoto, Masayo; Shindo, Motohiro; Iizuka, Naomi; Kohgo, Yutaka; Fujiya, Mikihiro

2016-08-01

Non-Tf-bound iron (NTBI), which appears in serum in iron overload, is thought to contribute to organ damage; the monitoring of serum NTBI levels may therefore be clinically useful in iron-overloaded patients. However, NTBI quantification methods remain complex, limiting their use in clinical practice. To overcome the technical difficulties often encountered, we recently developed a novel automated NTBI quantification system capable of measuring large numbers of samples. In the present study, we investigated the in vivo behavior of NTBI in human and animal serum using this newly established automated system. Average NTBI in healthy volunteers was 0.44 ± 0.076 μM (median 0.45 μM, range 0.28-0.66 μM), with no significant difference between sexes. Additionally, serum NTBI rapidly increased after iron loading, followed by a sudden disappearance. NTBI levels also decreased in inflammation. The results indicate that NTBI is a unique marker of iron metabolism, unlike other markers of iron metabolism, such as serum ferritin. Our new automated NTBI quantification method may help to reveal the clinical significance of NTBI and contribute to our understanding of iron overload.

Current Concepts in Hip Preservation Surgery

PubMed Central

Adler, Kelly L.; Cook, P. Christopher; Geisler, Paul R.; Yen, Yi-Meng; Giordano, Brian D.

2016-01-01

Context: Successful treatment of nonarthritic hip pain in young athletic individuals remains a challenge. A growing fund of clinical knowledge has paralleled technical innovations that have enabled hip preservation surgeons to address a multitude of structural variations of the proximal femur and acetabulum and concomitant intra-articular joint pathology. Often, a combination of open and arthroscopic techniques are necessary to treat more complex pathomorphologies. Peri- and postoperative recovery after such procedures can pose a substantial challenge to the patient, and a dedicated, thoughtful approach may reduce setbacks, limit morbidity, and help optimize functional outcomes. Evidence Acquisition: PubMed and CINAHL databases were searched to identify relevant scientific and review articles through December 2014 using the search terms hip preservation, labrum, surgical dislocation, femoroacetabular impingement, postoperative rehabilitation, peri-acetabular osteotomy, and rotational osteotomy. Reference lists of included articles were reviewed to locate additional references of interest. Study Design: Clinical review. Level of Evidence: Level 4. Results: Hip preservation procedures and appropriate rehabilitation have allowed individuals to return to a physically active lifestyle. Conclusion: Effective postoperative rehabilitation must consider modifications and precautions specific to the particular surgical techniques used. Proper postoperative rehabilitation after hip preservation surgery may help optimize functional recovery and maximize clinical success and patient satisfaction. PMID:26733593

Evaluation of matrix-assisted laser desorption/ionization time-of-fight mass spectrometry for identification of 345 clinical isolates of Aspergillus species from 11 Korean hospitals: comparison with molecular identification.

PubMed

Park, Ju Heon; Shin, Jong Hee; Choi, Min Ji; Choi, Jin Un; Park, Yeon-Joon; Jang, Sook Jin; Won, Eun Jeong; Kim, Soo Hyun; Kee, Seung Jung; Shin, Myung Geun; Suh, Soon Pal

2017-01-01

We evaluated the ability of the Filamentous Fungi Library 1.0 of the MALDI-TOF MS Biotyper system to identify 345 clinical Aspergillus isolates from 11 Korean hospitals. Compared with results of the internal transcribed spacer region sequencing, the frequencies of correct identification at the species-complex level were 94.5% and 98.8% with cutoff values of 2.0 and 1.7, respectively. Compared with results of β-tubulin gene sequencing, the frequencies of correct identification at the species level were 96.0% (cutoff 2.0) and 100% (cutoff 1.7) for 303 Aspergillus isolates of five common, non-cryptic species, but only 4.8% (cutoff 1.7) and 0% (cutoff 2.0) for 42 Aspergillus isolates of six cryptic species (identifiable by β-tubulin or calmodulin sequencing). These results show that the MALDI Biotyper using the Filamentous Fungi Library version 1.0 enables reliable identification of the majority of common clinical Aspergillus isolates, although the database should be expanded to facilitate identification of cryptic species. Copyright © 2016 Elsevier Inc. All rights reserved.

Status of therapeutic gene transfer to treat cardiovascular disease in dogs and cats.

PubMed

Sleeper, Meg; Bish, Lawrence T; Haskins, Mark; Ponder, Katherine P; Sweeney, H Lee

2011-06-01

Gene therapy is a procedure resulting in the transfer of a gene(s) into an individual's cells to treat a disease, which is designed to produce a protein or functional RNA (the gene product). Although most current gene therapy clinical trials focus on cancer and inherited diseases, multiple studies have evaluated the efficacy of gene therapy to abrogate various forms of heart disease. Indeed, human clinical trials are currently underway. One goal of gene transfer may be to express a functional gene when the endogenous gene is inactive. Alternatively, complex diseases such as end stage heart failure are characterized by a number of abnormalities at the cellular level, many of which can be targeted using gene delivery to alter myocardial protein levels. This review will discuss issues related to gene vector systems, gene delivery strategies and two cardiovascular diseases in dogs successfully treated with therapeutic gene delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparing Pharmacy Benefit Managers: Moving Well Beyond the Simple Spreadsheet Analysis

PubMed Central

Calabrese, David

2008-01-01

Unabated increases in prescription drug demands, advancing technology, and rising drug inflation rates combined with a sagging economy, continue to intensify budget pressures for payors responsible for delivering pharmacy benefits to plan members. At the same time, high levels of complexity and resource requirements in drug benefit administration have led to a state in which plan sponsors remain heavily dependent on pharmacy benefit managers to assist in these efforts. With pharmacy representing such a critical component of healthcare delivery from clinical and economic perspectives, it is essential that sponsors exercise high levels of due diligence in pharmacy benefit manager review and appraisal to ensure proper balance of quality clinical care, sufficient access, and optimal cost-efficiency in the delivery of such benefits. This review is designed to provide a comprehensive understanding of current pharmacy benefit management business practices and help equip plan sponsors with the knowledge, strategies, and safeguards to drive a well-informed pharmacy benefit selection process and, inevitably, a better-aligned pharmacy benefit management–payor relationship. PMID:25126235

Psychotherapy for PTSD: An evidence-based guide to a theranostic approach to treatment.

PubMed

Goodnight, Jessica R M; Ragsdale, Katie A; Rauch, Sheila A M; Rothbaum, Barbara O

2018-05-18

Posttraumatic stress disorder (PTSD) is often a clinically complex disorder, frequently presenting with comorbid clinical conditions. Individuals with PTSD may also present with high-risk symptoms such as substance misuse and suicidal ideation. The clinical complexity of PTSD has precluded some clinicians from providing gold-standard trauma-focused treatment due to concern of iatrogenic effects. However, evidence to date suggests that trauma-focused treatments are safe and effective for PTSD even when higher-risk comorbidity presents. Occasionally, while some patients present with clinical concerns that may benefit from modifications to standard recommended treatment protocols, research suggests there are few absolute contraindications to trauma-focused treatment. The present manuscript provides a review of evidence-based assessment and treatment recommendations for PTSD. A clinical decision-making guide for PTSD across areas of clinical complexity is provided. Copyright © 2018 Elsevier Inc. All rights reserved.

Rewards of bridging the divide between measurement and clinical theory: demonstration of a bifactor model for the Brief Symptom Inventory.

PubMed

Thomas, Michael L

2012-03-01

There is growing evidence that psychiatric disorders maintain hierarchical associations where general and domain-specific factors play prominent roles (see D. Watson, 2005). Standard, unidimensional measurement models can fail to capture the meaningful nuances of such complex latent variable structures. The present study examined the ability of the multidimensional item response theory bifactor model (see R. D. Gibbons & D. R. Hedeker, 1992) to improve construct validity by serving as a bridge between measurement and clinical theories. Archival data consisting of 688 outpatients' psychiatric diagnoses and item-level responses to the Brief Symptom Inventory (BSI; L. R. Derogatis, 1993) were extracted from files at a university mental health clinic. The bifactor model demonstrated superior fit for the internal structure of the BSI and improved overall diagnostic accuracy in the sample (73%) compared with unidimensional (61%) and oblique simple structure (65%) models. Consistent with clinical theory, multiple sources of item variance were drawn from individual test items. Test developers and clinical researchers are encouraged to consider model-based measurement in the assessment of psychiatric distress.

The third New Zealand Psychiatry of Old Age services and workforce survey.

PubMed

Cheung, Gary; Sims, Adam; Copeland, Bronwyn; Collins, Chris; Bharathan, Sires

2018-04-01

To survey the Psychiatry of Old Age (POA) services and workforce in New Zealand (NZ). The NZ branch of Faculty of POA contacted the POA lead clinician and/or service manager of the 20 district health boards (DHBs) and completed a survey based on variables used in two similar previous national surveys. Seventeen services responded. We found acute inpatient beds and clinical staff time are funded differently across DHBs. Although there has been an increase in non-medical clinical staff time in the community teams, most DHBs are not planning to increase their medical staff time in the next 3 years. Specialist services for people with intellectual disabilities and young-onset dementia, and older people with substance use disorder are generally not provided within POA services. A wider POA and non-POA services mapping is required to determine the level of services for clinical populations that have high and complex clinical needs. DHB funders should review the expected population growth in people aged 65+ and consider increasing the funding for these under-served clinical populations.

The Dreyfus model of clinical problem-solving skills acquisition: a critical perspective

PubMed Central

Peña, Adolfo

2010-01-01

Context The Dreyfus model describes how individuals progress through various levels in their acquisition of skills and subsumes ideas with regard to how individuals learn. Such a model is being accepted almost without debate from physicians to explain the ‘acquisition’ of clinical skills. Objectives This paper reviews such a model, discusses several controversial points, clarifies what kind of knowledge the model is about, and examines its coherence in terms of problem-solving skills. Dreyfus' main idea that intuition is a major aspect of expertise is also discussed in some detail. Relevant scientific evidence from cognitive science, psychology, and neuroscience is reviewed to accomplish these aims. Conclusions Although the Dreyfus model may partially explain the ‘acquisition’ of some skills, it is debatable if it can explain the acquisition of clinical skills. The complex nature of clinical problem-solving skills and the rich interplay between the implicit and explicit forms of knowledge must be taken into consideration when we want to explain ‘acquisition’ of clinical skills. The idea that experts work from intuition, not from reason, should be evaluated carefully. PMID:20563279

Addressing Low Literacy and Health Literacy in Clinical Oncology Practice

PubMed Central

Garcia, Sofia F.; Hahn, Elizabeth A.; Jacobs, Elizabeth A.

2011-01-01

Low functional literacy and low health literacy continue to be under-recognized and are associated with poorer patient health outcomes. Health literacy is a dynamic state influenced by how well a healthcare system delivers information and services that match patients’ abilities, needs and preferences. Oncology care poses considerable health literacy demands on patients who are expected to process high stakes information about complex multidisciplinary treatment over lengths of time. Much of the information provided to patients in clinical care and research is beyond their literacy levels. In this paper, we provide an overview of currently available guidelines and resources to improve how the needs of patients with diverse literacy skills are met by cancer care providers and clinics. We present recommendations for health literacy assessment in clinical practice and ways to enhance the usability of health information and services by improving written materials and verbal communication, incorporating multimedia and culturally appropriate approaches, and promoting health literacy in cancer care settings. The paper also includes a list of additional resources that can be used to develop and implement health literacy initiatives in cancer care clinics. PMID:20464884

Imagining with the body in analytical psychology. Movement as active imagination: an interdisciplinary perspective from philosophy and neuroscience.

PubMed

Deligiannis, Ana

2018-04-01

This article explores how the body and imagination operate as pathways of knowledge through the use of Movement as Active Imagination in clinical practice. This method activates the transcendent function, thus encouraging new therapeutic responses. A philosophical perspective (Spinoza, Nietzsche, Merleau-Ponty) and some concepts from neuroscience (embodied cognition, somatic markers, image schema, mirror neurons, neuronal plasticity) will accompany us throughout this work, illustrated with a clinical vignette. Three levels of integration: 1) body, 2) body-emotion, 3) body-emotion-imagination are proposed: these mark a progressive sense of articulation and complexity. Finally the relation between creativity and neuronal plasticity will be considered. © 2018, The Society of Analytical Psychology.

[Clinical pattern of epilepsy with abortive temporal lobe attacks].

PubMed

Dowzenko, A; Niedzielska-Zawadzka, K; Witkowska-Olearska, K; Jakubowska, T

1977-01-01

The purpose of the present work was to evaluate the clinical course of epilepsy with infrequent partial attacks with complex manifestations derived from the temporal lobe. Thirty patients aged 14 to 64 years treated on an outpatient basis and discovered during epidemiological investigations were followed-up. In half the cases only attacks without generalization occurred, in the remaining cases isolated generalized seizures appeared during many years of disease duration. In both groups a decrease was observed in the frequency of seizures in patients treated systematically or irregularly, as well as in those who had never been treated. Despite a long duration of the disease (above 6 years in 24 cases) the patients had normal mental level and good social adaptation.

Factoring nonviral gene therapy into a cure for hemophilia A.

PubMed

Gabrovsky, Vanessa; Calos, Michele P

2008-10-01

Gene therapy for hemophilia A has fallen short of success despite several clinical trials conducted over the past decade. Challenges to its success include vector immunogenicity, insufficient transgene expression levels of Factor VIII, and inhibitor antibody formation. Gene therapy has been dominated by the use of viral vectors, as well as the immunogenic and oncogenic concerns that accompany these strategies. Because of the complexity of viral vectors, the development of nonviral DNA delivery methods may provide an efficient and safe alternative for the treatment of hemophilia A. New types of nonviral strategies, such as DNA integrating vectors, and the success of several nonviral animal studies, suggest that nonviral gene therapy has curative potential and justifies its clinical development.

Intermittent maple syrup urine disease: two case reports.

PubMed

Axler, Olof; Holmquist, Peter

2014-02-01

The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain α-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or viral gastroenteritis triggers catabolism of muscle protein. Intermittent MSUD should be suspected in cases of common infections with a clinically atypical course, especially in children displaying ataxia or marked drowsiness.

The spectrum of psychosis in multiple sclerosis: a clinical case series

PubMed Central

Gilberthorpe, Thomas G; O’Connell, Kara E; Carolan, Alison; Silber, Eli; Brex, Peter A; Sibtain, Naomi A; David, Anthony S

2017-01-01

Psychosis in the context of multiple sclerosis (MS) has previously been reported as a rare occurrence. However, recent epidemiological studies have found prevalence rates of psychosis in MS that are two to three times higher than those in the general population. Untreated psychosis in patients with MS can adversely impact on adherence to MS medication, levels of disability, and quality of life. This retrospective case series describes the spectrum of psychotic disorders occurring in association with MS using demographic, clinical, and neuroimaging data. In the discussion, we highlight the particular diagnostic and treatment challenges that such disorders can pose for clinicians and through our case vignettes provide examples of potential interventions for this complex patient population. PMID:28203081

Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples

PubMed Central

White, James Robert; Nagarajan, Niranjan; Pop, Mihai

2009-01-01

Numerous studies are currently underway to characterize the microbial communities inhabiting our world. These studies aim to dramatically expand our understanding of the microbial biosphere and, more importantly, hope to reveal the secrets of the complex symbiotic relationship between us and our commensal bacterial microflora. An important prerequisite for such discoveries are computational tools that are able to rapidly and accurately compare large datasets generated from complex bacterial communities to identify features that distinguish them. We present a statistical method for comparing clinical metagenomic samples from two treatment populations on the basis of count data (e.g. as obtained through sequencing) to detect differentially abundant features. Our method, Metastats, employs the false discovery rate to improve specificity in high-complexity environments, and separately handles sparsely-sampled features using Fisher's exact test. Under a variety of simulations, we show that Metastats performs well compared to previously used methods, and significantly outperforms other methods for features with sparse counts. We demonstrate the utility of our method on several datasets including a 16S rRNA survey of obese and lean human gut microbiomes, COG functional profiles of infant and mature gut microbiomes, and bacterial and viral metabolic subsystem data inferred from random sequencing of 85 metagenomes. The application of our method to the obesity dataset reveals differences between obese and lean subjects not reported in the original study. For the COG and subsystem datasets, we provide the first statistically rigorous assessment of the differences between these populations. The methods described in this paper are the first to address clinical metagenomic datasets comprising samples from multiple subjects. Our methods are robust across datasets of varied complexity and sampling level. While designed for metagenomic applications, our software can also be applied to digital gene expression studies (e.g. SAGE). A web server implementation of our methods and freely available source code can be found at http://metastats.cbcb.umd.edu/. PMID:19360128

Interprofessional collaboration in the ICU: how to define?

PubMed

Rose, Louise

2011-01-01

The intensive care unit (ICU) is a dynamic, complex and, at times, highly stressful work environment that involves ongoing exposure to the complexities of interprofessional team functioning. Failures of communication, considered examples of poor collaboration among health care professionals, are the leading cause of inadvertent harm across all health care settings. Evidence suggests effective interprofessional collaboration results in improved outcomes for critically ill patients. One recent study demonstrated a link between low standardized mortality ratios and self-identified levels of collaboration. The aim of this paper is to discuss determinants and complexities of interprofessional collaboration, the evidence supporting its impact on outcomes in the ICU, and interventions designed to foster better interprofessional team functioning. Elements of effective interprofessional collaboration include shared goals and partnerships including explicit, complementary and interdependent roles; mutual respect; and power sharing. In the ICU setting, teams continually alter due to large staff numbers, shift work and staff rotations through the institution. Therefore, the ideal 'unified' team working together to provide better care and improve patient outcomes may be difficult to sustain. Power sharing is one of the most complex aspects of interprofessional collaboration. Ownership of specialized knowledge, technical skills, clinical territory, or even the patient, may produce interprofessional conflict when ownership is not acknowledged. Collaboration by definition implies interdependency as opposed to autonomy. Yet, much nursing literature focuses on achievement of autonomy in clinical decision-making, cited to improve job satisfaction, retention and patient outcomes. Autonomy of health care professionals may be an inappropriate goal when striving to foster interprofessional collaboration. Tools such as checklists, guidelines and protocols are advocated, by some, as ways for nurses to gain influence and autonomy in clinical decision-making. Protocols to guide ICU practices such as sedation and weaning reduce the duration of mechanical ventilation in some studies, while others have failed to demonstrate this advantage. Existing organizational strategies that facilitate effective collaboration between health care professionals may contribute to this lack of effect.

Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability.

PubMed

Zanchi, Davide; Cunningham, Gregory; Lädermann, Alexandre; Ozturk, Mehmet; Hoffmeyer, Pierre; Haller, Sven

2017-03-29

Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the post-operatory outcome. 13 patients with shoulder apprehension (30.03 ± 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

Circulating Plasma MicroRNA-208a as Potential Biomarker of Chronic Indeterminate Phase of Chagas Disease.

PubMed

Linhares-Lacerda, Leandra; Granato, Alessandra; Gomes-Neto, João Francisco; Conde, Luciana; Freire-de-Lima, Leonardo; de Freitas, Elisangela O; Freire-de-Lima, Celio G; Coutinho Barroso, Shana P; Jorge de Alcântara Guerra, Rodrigo; Pedrosa, Roberto C; Savino, Wilson; Morrot, Alexandre

2018-01-01

Chagas cardiomyopathy is the most severe clinical manifestation of chronic Chagas disease. The disease affects most of the Latin American countries, being considered one of the leading causes of morbidity and death in the continent. The pathogenesis of Chagas cardiomyopathy is very complex, with mechanisms involving parasite-dependent cytopathy, immune-mediated myocardial damage and neurogenic disturbances. These pathological changes eventually result in cardiac myocyte hypertrophy, arrhythmias, congestive heart failure and stroke during chronic infection phase. Herein, we show that miR-208a, a microRNA that is a key factor in promoting cardiovascular dysfunction during cardiac hypertrophy processes of heart failure, has its circulating levels increased during chronic indeterminate phase when compared to cardiac (CARD) clinical forms in patients with Chagas disease. In contrast, we have not found altered serum levels of miR-34a, a microRNA known to promote pro-apoptotic role in myocardial infarction during degenerative process of cardiac injuries thus indicating intrinsic differences in the nature of the mechanisms underlying the heart failure triggered by Trypanosoma cruzi infection. Our findings support that the chronic indeterminate phase is a progressive phase involved in the genesis of chagasic cardiopathy and point out the use of plasma levels of miR-208a as candidate biomarker in risk-prediction score for the clinical prognosis of Chagas disease.

[Necrobiotic xanthogranuloma in IgG kappa plasmacytoma and Quincke edema].

PubMed

Hafner, O; Witte, T; Schmidt, R E; Vakilzadeh, F

1994-05-01

Necrobiotic xanthogranuloma is a non-X histiocytosis with unknown pathogenesis. It is associated with paraproteinaemia, and in rare cases with multiple myeloma. A decreased level of C1 inhibitor has been found in several cases without clinical manifestations of Quincke oedema. We report on a patient with necrobiotic xanthogranuloma and myeloma, in whom we found a decreased level of C1 inhibitor and recurrent episodes of manifest Quincke oedema. The indirect detection of auto-antibodies against the paraprotein with development of immune complexes is regarded as an explanation for the consumption of the C1 inactivator and the manifestation of Quincke oedema. The possibility of a causal relationship between paraproteinaemia and necrotic xanthogranuloma is discussed.

Ionizing Radiation: The issue of radiation quality

NASA Astrophysics Data System (ADS)

Prise, Kevin; Schettino, Giuseppe

Types of Ionising radiations are differentiated from each other by fundamental characteristics of their energy deposition patterns when they interact with biological materials. At the level of the DNA these non-random patterns drive differences in the yields and distributions of DNA damage patterns and specifically the production of clustered damage or complex lesions. The complex radiation fields found in space bring significant challenges for developing a mechanistic understanding of radiation effects from the perspective of radiation quality as these consist of a diverse range of particle and energy types unique to the space environment. Linear energy transfer, energy deposited per unit track length in units of keV per micron, has long been used as a comparator for different types of radiation but has limitations in that it is an average value. Difference in primary core ionizations relative to secondary delta ray ranges vary significantly with particle mass and energy leading to complex interrelationships with damage production at the cellular level. At the cellular level a greater mechanistic understanding is necessary, linking energy deposition patterns to DNA damage patterns and cellular response, to build appropriate biophysical models that are predictive for different radiation qualities and mixed field exposures. Defined studies using monoenergetic beams delivered under controlled conditions are building quantitative data sets of both initial and long term changes in cells as a basis for a great mechanistic understanding of radiation quality effects of relevance to not only space exposures but clinical application of ion-beams.

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

PubMed Central

Gerschenson, Mariana; Chow, Dominic; Libutti, Daniel E.; Willis, John H.; Murray, James; Capaldi, Roderick A.; Marusich, Michael

2008-01-01

Abstract Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable surrogate marker in blood or other easily obtained clinical specimens as fat biopsies are invasive and mtDNA levels in peripheral blood mononuclear cells (PBMC) do not consistently correlate with the disease process. We used a simple, rapid, quantitative 2-site dipstick immunoassay to measure OXPHOS enzymes Complex I (CI) and Complex IV (CIV), and rtPCR to measure mtDNA in 26 matched SC fat and PBMC specimens previously banked from individuals on potent antiretroviral (ARV) therapy with HIV lipoatrophy, on similar ARV therapy without lipoatrophy, and in HIV seronegative controls. Significant correlations were found between the respective PBMC and fat levels for both CI (r = 0.442, p = 0.024) and for CIV (r = 0.507, p = 0.008). Both CI and CIV protein levels were also significantly reduced in both PBMCs and fat in lipoatrophic subjects compared to HIV seronegative controls (p ≤ 0.05), while a comparative reduction in mtDNA levels in lipoatrophic subjects was observed only in fat. We conclude that CI and CIV levels in PBMCs correlate to their respective levels in fat and may have utility as surrogate markers of mitochondrial dysfunction in lipoatrophy. PMID:18844460

Fractal Analysis of Visual Search Activity for Mass Detection During Mammographic Screening

DOE PAGES

Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy; ...

2017-02-21

Purpose: The objective of this study was to assess the complexity of human visual search activity during mammographic screening using fractal analysis and to investigate its relationship with case and reader characteristics. Methods: The study was performed for the task of mammographic screening with simultaneous viewing of four coordinated breast views as typically done in clinical practice. Eye-tracking data and diagnostic decisions collected for 100 mammographic cases (25 normal, 25 benign, 50 malignant) and 10 readers (three board certified radiologists and seven radiology residents), formed the corpus data for this study. The fractal dimension of the readers’ visual scanning patternsmore » was computed with the Minkowski–Bouligand box-counting method and used as a measure of gaze complexity. Individual factor and group-based interaction ANOVA analysis was performed to study the association between fractal dimension, case pathology, breast density, and reader experience level. The consistency of the observed trends depending on gaze data representation was also examined. Results: Case pathology, breast density, reader experience level, and individual reader differences are all independent predictors of the visual scanning pattern complexity when screening for breast cancer. No higher order effects were found to be significant. Conclusions: Fractal characterization of visual search behavior during mammographic screening is dependent on case properties and image reader characteristics.« less

Fractal analysis of radiologists' visual scanning pattern in screening mammography

NASA Astrophysics Data System (ADS)

Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy; Morin-Ducote, Garnetta; Tourassi, Georgia

2015-03-01

Several researchers have investigated radiologists' visual scanning patterns with respect to features such as total time examining a case, time to initially hit true lesions, number of hits, etc. The purpose of this study was to examine the complexity of the radiologists' visual scanning pattern when viewing 4-view mammographic cases, as they typically do in clinical practice. Gaze data were collected from 10 readers (3 breast imaging experts and 7 radiology residents) while reviewing 100 screening mammograms (24 normal, 26 benign, 50 malignant). The radiologists' scanpaths across the 4 mammographic views were mapped to a single 2-D image plane. Then, fractal analysis was applied on the composite 4- view scanpaths. For each case, the complexity of each radiologist's scanpath was measured using fractal dimension estimated with the box counting method. The association between the fractal dimension of the radiologists' visual scanpath, case pathology, case density, and radiologist experience was evaluated using fixed effects ANOVA. ANOVA showed that the complexity of the radiologists' visual search pattern in screening mammography is dependent on case specific attributes (breast parenchyma density and case pathology) as well as on reader attributes, namely experience level. Visual scanning patterns are significantly different for benign and malignant cases than for normal cases. There is also substantial inter-observer variability which cannot be explained only by experience level.

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

Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy

Purpose: The objective of this study was to assess the complexity of human visual search activity during mammographic screening using fractal analysis and to investigate its relationship with case and reader characteristics. Methods: The study was performed for the task of mammographic screening with simultaneous viewing of four coordinated breast views as typically done in clinical practice. Eye-tracking data and diagnostic decisions collected for 100 mammographic cases (25 normal, 25 benign, 50 malignant) and 10 readers (three board certified radiologists and seven radiology residents), formed the corpus data for this study. The fractal dimension of the readers’ visual scanning patternsmore » was computed with the Minkowski–Bouligand box-counting method and used as a measure of gaze complexity. Individual factor and group-based interaction ANOVA analysis was performed to study the association between fractal dimension, case pathology, breast density, and reader experience level. The consistency of the observed trends depending on gaze data representation was also examined. Results: Case pathology, breast density, reader experience level, and individual reader differences are all independent predictors of the visual scanning pattern complexity when screening for breast cancer. No higher order effects were found to be significant. Conclusions: Fractal characterization of visual search behavior during mammographic screening is dependent on case properties and image reader characteristics.« less

Real-World Implementation of Video Outpatient Consultations at Macro, Meso, and Micro Levels: Mixed-Method Study

PubMed Central

Wherton, Joseph; Vijayaraghavan, Shanti; Morris, Joanne; Bhattacharya, Satya; Hanson, Philippa; Campbell-Richards, Desirée; Ramoutar, Seendy; Collard, Anna; Hodkinson, Isabel

2018-01-01

Background There is much interest in virtual consultations using video technology. Randomized controlled trials have shown video consultations to be acceptable, safe, and effective in selected conditions and circumstances. However, this model has rarely been mainstreamed and sustained in real-world settings. Objective The study sought to (1) define good practice and inform implementation of video outpatient consultations and (2) generate transferable knowledge about challenges to scaling up and routinizing this service model. Methods A multilevel, mixed-method study of Skype video consultations (micro level) was embedded in an organizational case study (meso level), taking account of national context and wider influences (macro level). The study followed the introduction of video outpatient consultations in three clinical services (diabetes, diabetes antenatal, and cancer surgery) in a National Health Service trust (covering three hospitals) in London, United Kingdom. Data sources included 36 national-level stakeholders (exploratory and semistructured interviews), longitudinal organizational ethnography (300 hours of observations; 24 staff interviews), 30 videotaped remote consultations, 17 audiotaped face-to-face consultations, and national and local documents. Qualitative data, analyzed using sociotechnical change theories, addressed staff and patient experience and organizational and system drivers. Quantitative data, analyzed via descriptive statistics, included uptake of video consultations by staff and patients and microcategorization of different kinds of talk (using the Roter interaction analysis system). Results When clinical, technical, and practical preconditions were met, video consultations appeared safe and were popular with some patients and staff. Compared with face-to-face consultations for similar conditions, video consultations were very slightly shorter, patients did slightly more talking, and both parties sometimes needed to make explicit things that typically remained implicit in a traditional encounter. Video consultations appeared to work better when the clinician and patient already knew and trusted each other. Some clinicians used Skype adaptively to respond to patient requests for ad hoc encounters in a way that appeared to strengthen supported self-management. The reality of establishing video outpatient services in a busy and financially stretched acute hospital setting proved more complex and time-consuming than originally anticipated. By the end of this study, between 2% and 22% of consultations were being undertaken remotely by participating clinicians. In the remainder, clinicians chose not to participate, or video consultations were considered impractical, technically unachievable, or clinically inadvisable. Technical challenges were typically minor but potentially prohibitive. Conclusions Video outpatient consultations appear safe, effective, and convenient for patients in situations where participating clinicians judge them clinically appropriate, but such situations are a fraction of the overall clinic workload. As with other technological innovations, some clinicians will adopt readily, whereas others will need incentives and support. There are complex challenges to embedding video consultation services within routine practice in organizations that are hesitant to change, especially in times of austerity. PMID:29625956

Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis.

PubMed

Belcaro, G; Cesarone, M R; Dugall, M; Pellegrini, L; Ledda, A; Grossi, M G; Togni, S; Appendino, G

2010-06-01

A proprietary complex of curcumin with soy phosphatidylcholine (Meriva®, Indena SpA) was evaluated in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to 200 mg curcumin per diem. OA signs/symptoms were evaluated by the WOMAC scores. Mobility was studied by walking performance (treadmill), and inflammatory status was assessed by measurements of C-reactive protein (CRP). After three months of treatment, the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 +/- 12.3 to 112 +/- 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group. These results show that Meriva® is clinically effective in the management and treatment of osteoarthritis and suggest that the increased stability and better absorption of curcumin induced by complexation with phospholipids have clinical relevance, setting the stage for larger and more prolonged studies.

The nurse as bricoleur in falls prevention: learning from a case study of the implementation of fall prevention best practices.

PubMed

Kirkpatrick, Helen; Boblin, Sheryl; Ireland, Sandra; Robertson, Kim

2014-04-01

Falls prevention in "real-life" clinical practice is a complex undertaking. Nurses play an active and essential role in falls prevention. This discussion paper presents a picture of the nurse as a bricoleur in falls prevention, requiring knowledge in many areas and the ability to perform multiple diverse tasks. Building on a qualitative case study with nurses at various levels in three acute care facilities, this paper posits that the concept of nurse as bricoleur has the potential to broaden our understanding of the complexity of falls prevention. The nurse as bricoleur within the Promoting Action Research in Health Services framework as the provider of person- or patient-centered evidence-based care is conceptualized. Within this framework, the nurse uses his or her professional knowledge or clinical experience while considering research, local data, and information, and the patient's experience and preferences to provide this care, the bricolage. Each of these areas is discussed as well as the impact on the nurse when a fall does occur. Recognizing this complexity of the nurses' world has important implications for both service delivery and education, including preparation of students, and the implementation of new organizational initiatives and supports for nurses when falls do occur despite the best efforts of all involved. © 2014 Sigma Theta Tau International.

Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens* ,**

PubMed Central

Furini, Adriana Antônia da Cruz; Pedro, Heloisa da Silveira Paro; Rodrigues, Jean Francisco; Montenegro, Lilian Maria Lapa; Machado, Ricardo Luiz Dantas; Franco, Célia; Schindler, Haiana Charifker; Batista, Ida Maria Foschiani Dias; Rossit, Andrea Regina Baptista

2013-01-01

OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis. PMID:24473765

Severe polysaccharide storage myopathy in Belgian and Percheron draught horses.

PubMed

Valentine, B A; Credille, K M; Lavoie, J P; Fatone, S; Guard, C; Cummings, J F; Cooper, B J

1997-05-01

A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology of muscle from affected horses was the presence of excessive complex polysaccharide and/or glycogen, revealed by periodic acid-Schiff staining in all cases and by electron microscopy in one case. Evaluation of frozen section histochemistry performed on 2 cases indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and excessive glycogen, with little or no complex polysaccharide, was the primary compound stored in affected muscle in these young horses. Myopathic changes, including fibre size variation, fibre hypertrophy, internal nuclei, and interstitial fat infiltration, were most prominent in 5 horses age 6-21 years, and the accumulation of complex polysaccharide appeared to increase with age. Mild to moderate segmental myofibre necrosis was present in all cases.

Phenotypic interpretation of complex chromosomal rearrangements informed by nucleotide-level resolution and structural organization of chromatin.

PubMed

Zepeda-Mendoza, Cinthya J; Bardon, Alexandra; Kammin, Tammy; Harris, David J; Cox, Helen; Redin, Claire; Ordulu, Zehra; Talkowski, Michael E; Morton, Cynthia C

2018-03-01

Molecular characterization of balanced chromosomal abnormalities constitutes a powerful tool in understanding the pathogenic mechanisms of complex genetic disorders. Here we report a male with severe global developmental delay in the presence of a complex karyotype and normal microarray and exome studies. The subject, referred to as DGAP294, has two de novo apparently balanced translocations involving chromosomes 1 and 14, and chromosomes 4 and 10, disrupting several different transcripts of adhesion G protein-coupled receptor L2 (ADGRL2) and protocadherin 15 (PCDH15). In addition, a maternally inherited inversion disrupts peptidyl arginine deiminase types 3 and 4 (PADI3 and PADI4) on chromosome 1. None of these gene disruptions explain the patient's phenotype. Using genome regulatory annotations and chromosome conformation data, we predict a position effect ~370 kb upstream of a translocation breakpoint located at 14q12. The position effect involves forkhead box G1 (FOXG1), mutations in which are associated with the congenital form of Rett syndrome and FOXG1 syndrome. We believe the FOXG1 position effect largely accounts for the clinical phenotype in DGAP294, which can be classified as FOXG1 syndrome like. Our findings emphasize the significance of not only analyzing disrupted genes by chromosomal rearrangements, but also evaluating potential long-range position effects in clinical diagnoses.

Lead arthritis and lead poisoning following bullet wounds: a clinicopathologic, ultrastructural, and microanalytic study of two cases.

PubMed

Slavin, R E; Swedo, J; Cartwright, J; Viegas, S; Custer, E M

1988-02-01

Bullet wounds causing lead synovitis in the wrist and knee are reported in two patients, one of whom also developed clinical plumbism. Very high lead levels in the synovial fluid are believed to be responsible for toxicity changes that occurred in the synovium and bone. Ultrastructurally, these alterations included the formation of nuclear lead inclusions, dilation, and degranulation of the rough endoplasmic reticulum and deposition of crystalline precipitates in the matrix of the mitochondria in macrophages, osteoclasts, and synoviocytes, as well as the development of cytoplasmic lead inclusions in osteoclasts. Energy-dispersive x-ray elemental analysis (EDXEA) indicated that the nuclear inclusions contained only lead, whereas precipitates within the mitochondria and elsewhere in the cytoplasm were composed of complexes containing lead, calcium, and phosphorus. Similarly constituted extracellular complexes were incorporated into newly formed trabecular bone laid down as a physiologic response to the bullet lodged within the wrist bones. This bone subsequently exhibited defects in bone resorption, which were characterized by depressed osteoclastic function and a unique lesion termed incomplete osteocytic osteolysis. The genesis of this latter lesion is uncertain. The sequestration of the partially degraded bone fragments containing lead complexes into the marrow and eventually into the joint spaces and synovium permitted the recycling of bone lead, and this may have played an important role in inducing clinical plumbism in one of the patients in this study.

Distinct Subtypes of Microparticle-containing Immune Complexes Are Associated with Disease Activity, Damage, and Carotid Intima-media Thickness in Systemic Lupus Erythematosus.

PubMed

Fortin, Paul R; Cloutier, Nathalie; Bissonnette, Vincent; Aghdassi, Ellie; Eder, Lihi; Simonyan, David; Laflamme, Nathalie; Boilard, Eric

2016-11-01

Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP. MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage. We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use. Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

Towards a unified theory of health-disease: II. Holopathogenesis

PubMed Central

Almeida-Filho, Naomar

2014-01-01

This article presents a systematic framework for modeling several classes of illness-sickness-disease named as Holopathogenesis. Holopathogenesis is defined as processes of over-determination of diseases and related conditions taken as a whole, comprising selected facets of the complex object Health. First, a conceptual background of Holopathogenesis is presented as a series of significant interfaces (biomolecular-immunological, physiopathological-clinical, epidemiological-ecosocial). Second, propositions derived from Holopathogenesis are introduced in order to allow drawing the disease-illness-sickness complex as a hierarchical network of networks. Third, a formalization of intra- and inter-level correspondences, over-determination processes, effects and links of Holopathogenesis models is proposed. Finally, the Holopathogenesis frame is evaluated as a comprehensive theoretical pathology taken as a preliminary step towards a unified theory of health-disease. PMID:24897040

Primary Repair of Moderate Severity Rhegmatogenous Retinal Detachment: A Critical Decision-Making Algorithm.

PubMed

Velez-Montoya, Raul; Jacobo-Oceguera, Paola; Flores-Preciado, Javier; Dalma-Weiszhausz, Jose; Guerrero-Naranjo, Jose; Salcedo-Villanueva, Guillermo; Garcia-Aguirre, Gerardo; Fromow-Guerra, Jans; Morales-Canton, Virgilio

2016-01-01

We reviewed all the available data regarding the current management of non-complex rhegmatogenous retinal detachment and aimed to propose a new decision-making algorithm aimed to improve the single surgery success rate for mid-severity rhegmatogenous retinal detachment. An online review of the Pubmed database was performed. We searched for all available manuscripts about the anatomical and functional outcomes after the surgical management, by either scleral buckle or primary pars plana vitrectomy, of retinal detachment. The search was limited to articles published from January 1995 to December 2015. All articles obtained from the search were carefully screened and their references were manually reviewed for additional relevant data. Our search specifically focused on preoperative clinical data that were associated with the surgical outcomes. After categorizing the available data according to their level of evidence, with randomized-controlled clinical trials as the highest possible level of evidence, followed by retrospective studies, and retrospective case series as the lowest level of evidence, we proceeded to design a logical decision-making algorithm, enhanced by our experiences as retinal surgeons. A total of 7 randomized-controlled clinical trials, 19 retrospective studies, and 9 case series were considered. Additional articles were also included in order to support the observations further. Rhegmatogenous retinal detachment is a potentially blinding disorder. Its surgical management seems to depend more on a surgeon´s preference than solid scientific data or is based on a good clinical history and examination. The algorithms proposed herein strive to offer a more rational approach to improve both anatomical and functional outcomes after the first surgery.

Primary Repair of Moderate Severity Rhegmatogenous Retinal Detachment: A Critical Decision-Making Algorithm

PubMed Central

VELEZ-MONTOYA, Raul; JACOBO-OCEGUERA, Paola; FLORES-PRECIADO, Javier; DALMA-WEISZHAUSZ, Jose; GUERRERO-NARANJO, Jose; SALCEDO-VILLANUEVA, Guillermo; GARCIA-AGUIRRE, Gerardo; FROMOW-GUERRA, Jans; MORALES-CANTON, Virgilio

2016-01-01

We reviewed all the available data regarding the current management of non-complex rhegmatogenous retinal detachment and aimed to propose a new decision-making algorithm aimed to improve the single surgery success rate for mid-severity rhegmatogenous retinal detachment. An online review of the Pubmed database was performed. We searched for all available manuscripts about the anatomical and functional outcomes after the surgical management, by either scleral buckle or primary pars plana vitrectomy, of retinal detachment. The search was limited to articles published from January 1995 to December 2015. All articles obtained from the search were carefully screened and their references were manually reviewed for additional relevant data. Our search specifically focused on preoperative clinical data that were associated with the surgical outcomes. After categorizing the available data according to their level of evidence, with randomized-controlled clinical trials as the highest possible level of evidence, followed by retrospective studies, and retrospective case series as the lowest level of evidence, we proceeded to design a logical decision-making algorithm, enhanced by our experiences as retinal surgeons. A total of 7 randomized-controlled clinical trials, 19 retrospective studies, and 9 case series were considered. Additional articles were also included in order to support the observations further. Rhegmatogenous retinal detachment is a potentially blinding disorder. Its surgical management seems to depend more on a surgeon´s preference than solid scientific data or is based on a good clinical history and examination. The algorithms proposed herein strive to offer a more rational approach to improve both anatomical and functional outcomes after the first surgery. PMID:28289689

Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

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

Liu, Chenchen; Yue, Ben; Yuan, Chenwei

The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC)more » was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.« less

[The challenge of clinical complexity in the 21st century: Could frailty indexes be the answer?

PubMed

Amblàs-Novellas, Jordi; Espaulella-Panicot, Joan; Inzitari, Marco; Rexach, Lourdes; Fontecha, Benito; Romero-Ortuno, Roman

The number of older people with complex clinical conditions and complex care needs continues to increase in the population. This is presenting many challenges to healthcare professionals and healthcare systems. In the face of these challenges, approaches are required that are practical and feasible. The frailty paradigm may be an excellent opportunity to review and establish some of the principles of comprehensive Geriatric Assessment in specialties outside Geriatric Medicine. The assessment of frailty using Frailty Indexes provides an aid to the 'situational diagnosis' of complex clinical situations, and may help in tackling uncertainty in a person-centred approach. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Implementing electronic clinical reminders for lipid management in patients with ischemic heart disease in the veterans health administration: QUERI Series

PubMed Central

Sales, Anne; Helfrich, Christian; Ho, P Michael; Hedeen, Ashley; Plomondon, Mary E; Li, Yu-Fang; Connors, Alison; Rumsfeld, John S

2008-01-01

Background Ischemic heart disease (IHD) affects at least 150,000 veterans annually in the United States. Lowering serum cholesterol has been shown to reduce coronary events, cardiac death, and total mortality among high risk patients. Electronic clinical reminders available at the point of care delivery have been developed to improve lipid measurement and management in the Veterans Health Administration (VHA). Our objective was to report on a hospital-level intervention to implement and encourage use of the electronic clinical reminders. Methods The implementation used a quasi-experimental design with a comparison group of hospitals. In the intervention hospitals (N = 3), we used a multi-faceted intervention to encourage use of the electronic clinical reminders. We evaluated the degree of reminder use and how patient-level outcomes varied at the intervention and comparison sites (N = 3), with and without adjusting for self-reported reminder use. Results The national electronic clinical reminders were implemented in all of the intervention sites during the intervention period. A total of 5,438 patients with prior diagnosis of ischemic heart disease received care in the six hospitals (3 intervention and 3 comparison) throughout the 12-month intervention. The process evaluation showed variation in use of reminders at each site. Without controlling for provider self-report of use of the reminders, there appeared to be a significant improvement in lipid measurement in the intervention sites (OR 1.96, 95% CI 1.34, 2.88). Controlling for use of reminders, the amount of improvement in lipid measurement in the intervention sites was even greater (OR 2.35, CI 1.96, 2.81). Adjusting for reminder use demonstrated that only one of the intervention hospitals had a significant effect of the intervention. There was no significant change in management of hyperlipidemia associated with the intervention. Conclusion There may be some benefit to focused effort to implement electronic clinical reminders, although reminders designed to improve relatively simple tasks, such as ordering tests, may be more beneficial than reminders designed to improve more complex tasks, such as initiating or titrating medications, because of the less complex nature of the task. There is value in monitoring the process, as well as outcome, of an implementation effort. PMID:18510748

Effects of voice harmonic complexity on ERP responses to pitch-shifted auditory feedback.

PubMed

Behroozmand, Roozbeh; Korzyukov, Oleg; Larson, Charles R

2011-12-01

The present study investigated the neural mechanisms of voice pitch control for different levels of harmonic complexity in the auditory feedback. Event-related potentials (ERPs) were recorded in response to+200 cents pitch perturbations in the auditory feedback of self-produced natural human vocalizations, complex and pure tone stimuli during active vocalization and passive listening conditions. During active vocal production, ERP amplitudes were largest in response to pitch shifts in the natural voice, moderately large for non-voice complex stimuli and smallest for the pure tones. However, during passive listening, neural responses were equally large for pitch shifts in voice and non-voice complex stimuli but still larger than that for pure tones. These findings suggest that pitch change detection is facilitated for spectrally rich sounds such as natural human voice and non-voice complex stimuli compared with pure tones. Vocalization-induced increase in neural responses for voice feedback suggests that sensory processing of naturally-produced complex sounds such as human voice is enhanced by means of motor-driven mechanisms (e.g. efference copies) during vocal production. This enhancement may enable the audio-vocal system to more effectively detect and correct for vocal errors in the feedback of natural human vocalizations to maintain an intended vocal output for speaking. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

PubMed

Chen, Zhi-Hai; Qin, Xin-Cheng; Song, Rui; Shen, Yi; Chen, Xiao-Ping; Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C; Zhang, Yong-Zhen

2014-01-01

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

Neuroactive steroids and PTSD treatment.

PubMed

Rasmusson, Ann M; Marx, Christine E; Pineles, Suzanne L; Locci, Andrea; Scioli-Salter, Erica R; Nillni, Yael I; Liang, Jennifer J; Pinna, Graziano

2017-05-10

This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain. Nevertheless, large naturalistic studies and a small placebo-controlled interventional study have revealed generally positive effects of glucocorticoid administration in preventing PTSD after trauma, possibly mediated by glucocorticoid receptor-mediated effects on other targets that impact PTSD risk, including other neuroactive steroid systems. In addition, clinical and preclinical studies show that administration of glucocorticoids, 17β-estradiol, and GABAergic neuroactive steroids or agents that enhance their synthesis can facilitate extinction and extinction retention, depending on dose and timing of dose in relation to these complex PTSD-relevant recovery processes. This suggests that clinical trials designed to test neuroactive steroid therapeutics in PTSD may benefit from such considerations; typical continuous dosing regimens may not be optimal. In addition, validated and clinically accessible methods for identifying specific neuroactive steroid system abnormalities at the individual level are needed to optimize both clinical trial design and precision medicine based treatment targeting. Copyright © 2017. Published by Elsevier B.V.

HYPOTHYROIDISM - A SPECIAL COMORBIDITY FACTOR IN PATIENTS WITH OSTEOARTHROSIS: CLINICAL, PATHOPHYSIOLOGICAL AND PROGNOSTIC ASPECTS.

PubMed

Voloshyna, L; Doholich, О; Sithinska, I

2017-11-01

Objective - to study the features of the functional and morphological condition of the thyroid gland (TG) in patients with osteoarthrosis (OA), the incidence and forms of hypothyroidism and their effects on clinical manifestations, metabolic disorders and the results of the treatment of OA and comorbid processes. A complex examination involved 312 patients with OA aged 37-76 years. Methods used: anthropometric, clinical, ultrasonographic, biochemical, radioimmunological (levels of TSH, free thyroxine, antibodies to thyroid peroxidase). It has been established that with increasing age in patients OA phenomena are progressing, there is an increase in comorbid diseases, especially of the cardiovascular system with atherosclerotic genesis, they become more severe. Against this background, clinical hypothyroidism was found in 4.44% and subclinical one in 13.78%. Stratification of the clinical form of hypothyroidism contributed to the deterioration of the course and outcome of the treatment of OA and comorbid diseases. Both forms of hypothyroidism intensified the degrees of metabolic disorders in the blood, reduced the glomerular filtration rate, especially the clinical form. Manifestations of hypothyroidism were observed in patients with OA with its significant systemic manifestations, high comorbidity rate, in individuals aged over 50, especially 60 years, mainly in women (83,72%). In patients with OA aged over 50 years with a high comorbidity rate, it is advisable to conduct an ultrasound examination of the thyroid gland, to measure the levels of TSH, free thyroxine in order to diagnose hypothyroidism early and to treat it timely as one of the ways to improve the overall outcomes of the treatment of such patients.

Evaluation of a tissue-engineered bovine pericardial patch in paediatric patients with congenital cardiac anomalies: initial experience with the ADAPT-treated CardioCel(R) patch.

PubMed

Neethling, William M L; Strange, Geoff; Firth, Laura; Smit, Francis E

2013-10-01

This study evaluated the safety, efficacy and clinical performance of the tissue-engineered ADAPT® bovine pericardial patch (ABPP) in paediatric patients with a range of congenital cardiac anomalies. In this single-centre, prospective, non-randomized clinical study, paediatric patients underwent surgery for insertion of the ABPP. Primary efficacy measures included early (<30 day) morbidity; incidence of device-related complications; haemodynamic performance derived from echocardiography assessment at 6- and 12-month follow-up and magnetic resonance imaging findings in 10 randomly selected patients at 12 months. Secondary measures included device-handling characteristics; shape and sizing characteristics and perioperative implant complications. The Aristotle complexity scoring system was used to score the complexity level of all surgical procedures. Patients completing the 12-month study were eligible to enter a long-term evaluation study. Between April 2008 and September 2009, the ABPP was used in 30 paediatric patients. In the 30-day postoperative period, no graft-related morbidity was observed. In total, there were 5 deaths (2 in the 30-day postoperative period and 3 within the first 6 postoperative months). All deaths were deemed due to comorbid non-graft-related events. Echocardiography assessment at 6 and 12 months revealed intact anatomical and haemodynamically stable repairs without any visible calcification of the patch. Magnetic resonance imaging assessment in 10 patients at 12 months revealed no signs of calcification. Fisher's exact test demonstrated that patients undergoing more complex, higher risk surgical repairs (Aristotle complexity score >8) were significantly more likely to die (P = 0.0055, 58% survival compared with 100% survival for less complex surgical repairs). In 19 patients, echocardiographic data were available at 18-36 months with no evidence of device calcification, infection, thromboembolic events or device failure. This study demonstrates the safety and efficacy of this engineered bovine pericardial patch as a cardiovascular substitute for surgical repair of both simple and more complex congenital cardiac defects.

Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

PubMed Central

Overington, Jeff D.; Huang, Yao C.; Abramson, Michael J.; Brown, Juliet L.; Goddard, John R.; Bowman, Rayleen V.; Fong, Kwun M.

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care. PMID:25478199

Ambiguity Within Nursing Practice: An Evolutionary Concept Analysis.

PubMed

McMahon, Michelle A; Dluhy, Nancy M

2017-02-01

To analyze the concept of ambiguity in a nursing context. Ambiguity is inherent within nursing practice. As health care becomes increasingly complex, nurses must continue to successfully deal with greater amounts of clinical ambiguity. Although ambiguity is discussed in nursing, minimal concept refinement exists to capture the contextual intricacies from a nursing lens. Nurse perception of an ambiguous clinical event, in combination with nurse tolerance level for ambiguity, can impact nurse response. Yet, little is known about what constitutes ambiguity within nursing practice (AWNP). Rodgers evolutionary method was used to explore AWNP, with emphasis on nurse thinking during ambiguous clinical situations. Literature searches across multiple databases yielded 38 articles for analysis. Attributes of AWNP include (a) variations in cues/available information, (b) multiple interpretations, (c) novel/nonroutine presentations, and (d) unpredictable. Antecedents include (a) a context-specific, clinical situation with ambiguous features needing evaluation and (b) an individual to sense a knowledge gap or perceive ambiguity. Consequences include ranges of (a) emotional, (b) behavioral, and (c) cognitive clinician responses. Preliminary findings support AWNP as a distinct concept in which ambiguity perceived by the nurse likely affects judgment, decision making, and clinical interventions. AWNP is a clinically relevant concept requiring continued development.

Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache.

PubMed

Strittmatter, M; Hamann, G F; Grauer, M; Fischer, C; Blaes, F; Hoffmann, K H; Schimrigk, K

1996-05-17

Twelve patients (age 43.4 +/- 6.3 years) with episodic cluster headache (CH) were examined during the cluster period. Plasma norepinephrine levels in patients suffering from CH were significantly decreased compared with the control group (p < 0.01). There were also statistically significant correlations between norepinephrine levels and clinical features of the pain attacks including duration (r = 0.75, p < 0.05), intensity (r = 0.64, p < 0.05) and frequency (r = 0.68, p < 0.06), thereby suggesting a pathophysiological involvement of the sympathetic nervous system in CH. Increased plasma levels of plasmacortisol and ACTH in patients with CH, especially in the morning and in the evening, suggest an alteration of the feedback circuit involving the hypothalamus, the pituitary and the adrenal gland, an imbalance in the hormones related to these structures, as well as an alteration of the circadian rhythm. In addition, CH patients demonstrated significantly decreased levels of norepinephrine (p < 0.05), HVA (p < 0.01) and 5-HIAA (p < 0.01) in the cerebrospinal fluid (CSF) consistent with a central genesis of CH. These significant relationships between neurochemical parameters and the clinical patterns suggest a complex interplay between the hypothalamus, neuroendocrinological parameters, activity of the autonomic nervous system and the pain of CH.

Team Learning for Healthcare Quality Improvement

PubMed Central

Eppstein, Margaret J.; Horbar, Jeffrey D.

2014-01-01

In organized healthcare quality improvement collaboratives (QICs), teams of practitioners from different hospitals exchange information on clinical practices with the aim of improving health outcomes at their own institutions. However, what works in one hospital may not work in others with different local contexts because of nonlinear interactions among various demographics, treatments, and practices. In previous studies of collaborations where the goal is a collective problem solving, teams of diverse individuals have been shown to outperform teams of similar individuals. However, when the purpose of collaboration is knowledge diffusion in complex environments, it is not clear whether team diversity will help or hinder effective learning. In this paper, we first use an agent-based model of QICs to show that teams comprising similar individuals outperform those with more diverse individuals under nearly all conditions, and that this advantage increases with the complexity of the landscape and level of noise in assessing performance. Examination of data from a network of real hospitals provides encouraging evidence of a high degree of similarity in clinical practices, especially within teams of hospitals engaging in QIC teams. However, our model also suggests that groups of similar hospitals could benefit from larger teams and more open sharing of details on clinical outcomes than is currently the norm. To facilitate this, we propose a secure virtual collaboration system that would allow hospitals to efficiently identify potentially better practices in use at other institutions similar to theirs without any institutions having to sacrifice the privacy of their own data. Our results may also have implications for other types of data-driven diffusive learning such as in personalized medicine and evolutionary search in noisy, complex combinatorial optimization problems. PMID:25360395

Kaizen practice in healthcare: a qualitative analysis of hospital employees' suggestions for improvement

PubMed Central

Mazzocato, Pamela; Stenfors-Hayes, Terese; von Thiele Schwarz, Ulrica; Hasson, Henna

2016-01-01

Objectives Kaizen, or continuous improvement, lies at the core of lean. Kaizen is implemented through practices that enable employees to propose ideas for improvement and solve problems. The aim of this study is to describe the types of issues and improvement suggestions that hospital employees feel empowered to address through kaizen practices in order to understand when and how kaizen is used in healthcare. Methods We analysed 186 structured kaizen documents containing improvement suggestions that were produced by 165 employees at a Swedish hospital. Directed content analysis was used to categorise the suggestions into following categories: type of situation (proactive or reactive) triggering an action; type of process addressed (technical/administrative, support and clinical); complexity level (simple or complex); and type of outcomes aimed for (operational or sociotechnical). Compliance to the kaizen template was calculated. Results 72% of the improvement suggestions were reactions to a perceived problem. Support, technical and administrative, and primary clinical processes were involved in 47%, 38% and 16% of the suggestions, respectively. The majority of the kaizen documents addressed simple situations and focused on operational outcomes. The degree of compliance to the kaizen template was high for several items concerning the identification of problems and the proposed solutions, and low for items related to the test and implementation of solutions. Conclusions There is a need to combine kaizen practices with improvement and innovation practices that help staff and managers to address complex issues, such as the improvement of clinical care processes. The limited focus on sociotechnical aspects and the partial compliance to kaizen templates may indicate a limited understanding of the entire kaizen process and of how it relates to the overall organisational goals. This in turn can hamper the sustainability of kaizen practices and results. PMID:27473953

The BioIntelligence Framework: a new computational platform for biomedical knowledge computing.

PubMed

Farley, Toni; Kiefer, Jeff; Lee, Preston; Von Hoff, Daniel; Trent, Jeffrey M; Colbourn, Charles; Mousses, Spyro

2013-01-01

Breakthroughs in molecular profiling technologies are enabling a new data-intensive approach to biomedical research, with the potential to revolutionize how we study, manage, and treat complex diseases. The next great challenge for clinical applications of these innovations will be to create scalable computational solutions for intelligently linking complex biomedical patient data to clinically actionable knowledge. Traditional database management systems (DBMS) are not well suited to representing complex syntactic and semantic relationships in unstructured biomedical information, introducing barriers to realizing such solutions. We propose a scalable computational framework for addressing this need, which leverages a hypergraph-based data model and query language that may be better suited for representing complex multi-lateral, multi-scalar, and multi-dimensional relationships. We also discuss how this framework can be used to create rapid learning knowledge base systems to intelligently capture and relate complex patient data to biomedical knowledge in order to automate the recovery of clinically actionable information.

Improving outcomes of first‐episode psychosis: an overview

PubMed Central

Fusar‐Poli, Paolo; McGorry, Patrick D.; Kane, John M.

2017-01-01

Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state‐of‐the‐art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients’ satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well‐being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre‐emptive interventions to high‐risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders. PMID:28941089

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

PubMed

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

Nanoparticles speckled by ready-to-conjugate lanthanide complexes for multimodal imaging

NASA Astrophysics Data System (ADS)

Biju, Vasudevanpillai; Hamada, Morihiko; Ono, Kenji; Sugino, Sakiko; Ohnishi, Takashi; Shibu, Edakkattuparambil Sidharth; Yamamura, Shohei; Sawada, Makoto; Nakanishi, Shunsuke; Shigeri, Yasushi; Wakida, Shin-Ichi

2015-09-01

Multimodal and multifunctional contrast agents receive enormous attention in the biomedical imaging field. Such contrast agents are routinely prepared by the incorporation of organic molecules and inorganic nanoparticles (NPs) into host materials such as gold NPs, silica NPs, polymer NPs, and liposomes. Despite their non-cytotoxic nature, the large size of these NPs limits the in vivo distribution and clearance and inflames complex pharmacokinetics, which hinder the regulatory approval for clinical applications. Herein, we report a unique method that combines magnetic resonance imaging (MRI) and fluorescence imaging modalities together in nanoscale entities by the simple, direct and stable conjugation of novel biotinylated coordination complexes of gadolinium(iii) to CdSe/ZnS quantum dots (QD) and terbium(iii) to super paramagnetic iron oxide NPs (SPION) but without any host material. Subsequently, we evaluate the potentials of such lanthanide-speckled fluorescent-magnetic NPs for bioimaging at single-molecule, cell and in vivo levels. The simple preparation and small size make such fluorescent-magnetic NPs promising contrast agents for biomedical imaging.

Construction of a functional silk-based biomaterial complex with immortalized chondrocytes in vivo.

PubMed

Ni, Yusu; Jiang, Yi; Wen, Jianchuan; Shao, Zhenzhong; Chen, Xin; Sun, Shan; Yu, Huiqian; Li, Wen

2014-04-01

To explore the feasibility of constructing a functional biomaterial complex with regenerated silk fibroin membrane and immortalized chondrocytes in vivo. Rat auricular chondrocytes (RACs) were transfected with the lentivirus vector pGC-FU-hTERT-3FLAG or pGC-FU-GFP-3FLAG, encoding the human telomerase reverse transcriptase (hTERT) or GFP gene. The effects of regenerated silk fibroin film on the adhesion, growth of immortalized chondrocytes and expression of collagen II in vitro were analyzed with immunofluorescent histochemistry. Immortalized RACs were transformed. Induction by nutrient medium promoted higher expression levels of collagen II in transformed chondrocytes. The regenerated silk fibroin film was not cytotoxic to immortalized chondrocytes and had no adverse influence on their adhesion. Collagen II expression was good in the immortalized chondrocytes in vivo. The construction of a silk-based biomaterial complex with immortalized chondrocytes may provide a feasible kind of functional biomaterial for the repair of cartilage defects in clinical applications. Copyright © 2013 Wiley Periodicals, Inc.

Data Science in the Research Domain Criteria Era: Relevance of Machine Learning to the Study of Stress Pathology, Recovery, and Resilience

PubMed Central

Galatzer-Levy, Isaac R.; Ruggles, Kelly; Chen, Zhe

2017-01-01

Diverse environmental and biological systems interact to influence individual differences in response to environmental stress. Understanding the nature of these complex relationships can enhance the development of methods to: (1) identify risk, (2) classify individuals as healthy or ill, (3) understand mechanisms of change, and (4) develop effective treatments. The Research Domain Criteria (RDoC) initiative provides a theoretical framework to understand health and illness as the product of multiple inter-related systems but does not provide a framework to characterize or statistically evaluate such complex relationships. Characterizing and statistically evaluating models that integrate multiple levels (e.g. synapses, genes, environmental factors) as they relate to outcomes that a free from prior diagnostic benchmarks represents a challenge requiring new computational tools that are capable to capture complex relationships and identify clinically relevant populations. In the current review, we will summarize machine learning methods that can achieve these goals. PMID:29527592

What factors influence time-use of occupational therapists in the workplace? A systematic review.

PubMed

Summers, Bianca E; Laver, Kate E; Nicks, Rebecca J; Lannin, Natasha A

2018-06-01

Health-care expenditure is rapidly increasing in Australia with increasing pressure on health-care services to review processes, improve efficiency and ensure equity in service delivery. The nursing profession have improved efficiency and patient care by investigating time-use to describe current practice and support development of workforce planning models. There is, however, a lack of information to understand factors that impact on occupational therapists time-use in the clinical setting impacting the development of workforce planning models which adapt occupational therapy service delivery to match resources with demand. The objective of this review was to systematically identify known factors which impact on occupational therapists time-use in the clinical setting. A systematic review of Medline, PsycINFO and CINAHL databases and grey literature was completed in September 2016. Two authors independently screened studies for inclusion and quality was evaluated using the Downs and Black scale. Variables impacting on occupational therapists time-use were categorised and thematically analysed to synthesise key themes. Twenty studies met the inclusion criteria and were included in the review. Three key categories of factors influencing time-use were identified. These were: patient-related factors (e.g. level of function, therapy required, type, complexity of injury), therapist-related factors (e.g. experience, clinical vs non-clinical responsibility), and organisational-related factors (e.g. workplace characteristics, availability of staff, presence of students). Occupational therapist time-use in clinical settings is complex and difficult to quantify in research. How occupational therapists spend their time is impacted by a number of patient, clinician and service related factors reflecting the breadth of occupational therapy practice and client-centred nature of the profession. © 2018 Occupational Therapy Australia.

Species Identification and In Vitro Antifungal Susceptibility of Aspergillus terreus Species Complex Clinical Isolates from a French Multicenter Study.

PubMed

Imbert, S; Normand, A C; Ranque, S; Costa, J M; Guitard, J; Accoceberry, I; Bonnal, C; Fekkar, A; Bourgeois, N; Houzé, S; Hennequin, C; Piarroux, R; Dannaoui, E; Botterel, F

2018-05-01

Aspergillus section Terrei is a species complex currently comprised of 14 cryptic species whose prevalence in clinical samples as well as antifungal susceptibility are poorly known. The aims of this study were to investigate A. Terrei clinical isolates at the species level and to perform antifungal susceptibility analyses by reference and commercial methods. Eighty-two clinical A. Terrei isolates were collected from 8 French university hospitals. Molecular identification was performed by sequencing parts of beta-tubulin and calmodulin genes. MICs or minimum effective concentrations (MECs) were determined for 8 antifungal drugs using both EUCAST broth microdilution (BMD) methods and concentration gradient strips (CGS). Among the 79 A. Terrei isolates, A. terreus stricto sensu ( n = 61), A. citrinoterreus ( n = 13), A. hortai ( n = 3), and A. alabamensis ( n = 2) were identified. All strains had MICs of ≥1 mg/liter for amphotericin B, except for two isolates (both A. hortai ) that had MICs of 0.25 mg/liter. Four A. terreus isolates were resistant to at least one azole drug, including one with pan-azole resistance, yet no mutation in the CYP51A gene was found. All strains had low MECs for the three echinocandins. The essential agreements (EAs) between BMD and CGS were >90%, except for those of amphotericin B (79.7%) and itraconazole (73.4%). Isolates belonging to the A section Terrei identified in clinical samples show wider species diversity beyond the known A. terreus sensu stricto Azole resistance inside the section Terrei is uncommon and is not related to CYP51A mutations here. Finally, CGS is an interesting alternative for routine antifungal susceptibility testing. Copyright © 2018 American Society for Microbiology.

The weak relationship between anatomy competence and clinical skills in junior medical students.

PubMed

Schoeman, Scarpa; Chandratilake, Madawa

2012-01-01

In modern curricula, the early integration of anatomy and clinical skills education at undergraduate level is seen as important. However, the direct relationship between medical students' competence in anatomy, and their clinical proficiency during early undergraduate years, has scarcely been studied. In this study, the marks for anatomy and clinical skills of three consecutive cohorts of medical students (n = 538 in total) during their first two years were correlated. The anatomy competence was measured using a new marker, the Anatomy Competence Score (ACS) which was calculated with equal contributions from theory knowledge and its practical and clinical application. Proficiency in clinical skills was determined by OSCE performance marks for stations which examined physical examination and practical procedural skills. The possible compounding effect of students' general academic ability was investigated by using the overall performance mark for each student based on their performance in all subjects over the first two years of the medical curriculum. We found that the correlation between anatomy and clinical skills marks was weak to moderate. However, this correlation was virtually nullified once the effect of academic ability was accounted for. Although these findings suggest that anatomy education does not compliment early clinical education, the lack of complexity of clinical problems used in clinical skills assessments (OSCEs) during the early stages may well be the primary contributing factor to this finding. Copyright © 2012 American Association of Anatomists.

EQUIP Healthcare: An overview of a multi-component intervention to enhance equity-oriented care in primary health care settings.

PubMed

Browne, Annette J; Varcoe, Colleen; Ford-Gilboe, Marilyn; Wathen, C Nadine

2015-12-14

The primary health care (PHC) sector is increasingly relevant as a site for population health interventions, particularly in relation to marginalized groups, where the greatest gains in health status can be achieved. The purpose of this paper is to provide an overview of an innovative multi-component, organizational-level intervention designed to enhance the capacity of PHC clinics to provide equity-oriented care, particularly for marginalized populations. The intervention, known as EQUIP, is being implemented in Canada in four diverse PHC clinics serving populations who are impacted by structural inequities. These PHC clinics serve as case studies for the implementation and evaluation of the EQUIP intervention. We discuss the evidence and theory that provide the basis for the intervention, describe the intervention components, and discuss the methods used to evaluate the implementation and impact of the intervention in diverse contexts. Research and theory related to equity-oriented care, and complexity theory, are central to the design of the EQUIP intervention. The intervention aims to enhance capacity for equity-oriented care at the staff level, and at the organizational level (i.e., policy and operations) and is novel in its dual focus on: (a) Staff education: using standardized educational models and integration strategies to enhance staff knowledge, attitudes and practices related to equity-oriented care in general, and cultural safety, and trauma- and violence-informed care in particular, and; (b) Organizational integration and tailoring: using a participatory approach, practice facilitation, and catalyst grants to foster shifts in organizational structures, practices and policies to enhance the capacity to deliver equity-oriented care, improve processes of care, and shift key client outcomes. Using a mixed methods, multiple case-study design, we are examining the impact of the intervention in enhancing staff knowledge, attitudes and practices; improving processes of care; shifting organizational policies and structures; and improving selected client outcomes. The multiple case study design provides an ideal opportunity to study the contextual factors shaping the implementation, uptake and impact of our tailored intervention within diverse PHC settings. The EQUIP intervention illustrates the complexities involved in enhancing the PHC sector's capacity to provide equity-oriented care in real world clinical contexts.

Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction.

PubMed

Kjellqvist, Sanela; Klose, Christian; Surma, Michal A; Hindy, George; Mollet, Inês G; Johansson, Anna; Chavaux, Patrick; Gottfries, Johan; Simons, Kai; Melander, Olle; Fernandez, Céline

2016-11-29

Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmö Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18:2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18:2 (P≤0.007) and lower desaturase activity (P≤0.002). We demonstrate a possible relationship between decreased levels of C18:2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Dynamics of Concussion: Mapping Pathophysiology, Persistence, and Recovery With Causal-Loop Diagramming

PubMed Central

Kenzie, Erin S.; Parks, Elle L.; Bigler, Erin D.; Wright, David W.; Lim, Miranda M.; Chesnutt, James C.; Hawryluk, Gregory W. J.; Gordon, Wayne; Wakeland, Wayne

2018-01-01

Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury. The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits. The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences. Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication—all strides that would benefit diagnosis, prognosis, and treatment in the clinic. PMID:29670568

Toward modeling locomotion using electromyography-informed 3D models: application to cerebral palsy.

PubMed

Sartori, M; Fernandez, J W; Modenese, L; Carty, C P; Barber, L A; Oberhofer, K; Zhang, J; Handsfield, G G; Stott, N S; Besier, T F; Farina, D; Lloyd, D G

2017-03-01

This position paper proposes a modeling pipeline to develop clinically relevant neuromusculoskeletal models to understand and treat complex neurological disorders. Although applicable to a variety of neurological conditions, we provide direct pipeline applicative examples in the context of cerebral palsy (CP). This paper highlights technologies in: (1) patient-specific segmental rigid body models developed from magnetic resonance imaging for use in inverse kinematics and inverse dynamics pipelines; (2) efficient population-based approaches to derive skeletal models and muscle origins/insertions that are useful for population statistics and consistent creation of continuum models; (3) continuum muscle descriptions to account for complex muscle architecture including spatially varying material properties with muscle wrapping; (4) muscle and tendon properties specific to CP; and (5) neural-based electromyography-informed methods for muscle force prediction. This represents a novel modeling pipeline that couples for the first time electromyography extracted features of disrupted neuromuscular behavior with advanced numerical methods for modeling CP-specific musculoskeletal morphology and function. The translation of such pipeline to the clinical level will provide a new class of biomarkers that objectively describe the neuromusculoskeletal determinants of pathological locomotion and complement current clinical assessment techniques, which often rely on subjective judgment. WIREs Syst Biol Med 2017, 9:e1368. doi: 10.1002/wsbm.1368 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Osteoarthritis of the ankle and foot complex in former Greek soccer players.

PubMed

Armenis, Elias; Pefanis, Nikolaos; Tsiganos, Georgios; Karagounis, Panagiotis; Baltopoulos, Panagiotis

2011-12-01

Sports activities cause increased loads in elite athletes' joints. Current scientific knowledge highlights the importance of applied mechanical loads on the physiology and pathophysiology of the articular cartilage. Thus, it is possible that sporting activity has a role in the development of osteoarthritis (OA), a painful and damaging joint disease. The aim of the present study was to investigate and record osteoarthritic alterations in the ankle and foot complex in former Greek soccer players and also compare them with those in the general population. The study sample consisted of 170 male, former elite soccer players, aged between 42 and 55 years (mean = 49.8 years, standard deviation [SD] = 7.4). A control group of 132 men, aged between 42 and 55 years (mean, 50.7 years, SD = 9.9), with no regular athletic activity were examined. The development of osteoarthritic alterations was recorded through a questionnaire and clinical and radiological examination. Radiographic analysis of the images in former athletes group showed not only more signs of cartilage degeneration in comparison with the control group (P < .05) but also similar clinical manifestations (pain and impaired mobility; P > .05). Osteophyte formation is a frequent disease among former soccer players--with variations on radiographic images--but it does not appear in their clinical picture. However, it is likely that both spurs and subchondral sclerosis (main findings) are preclinical manifestations of OA. Prognostic, Level II.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

PubMed

Kwon, Yong-Soo; Koh, Won-Jung

2016-05-01

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies.

PubMed

Boscarino, Joseph A

2004-12-01

Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor-induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T-cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T-cell counts, hyperreactive immune responses on standardized delayed cutaneous hypersensitivity tests, clinically higher immunoglobulin-M levels, and clinically lower dehydroepiandrosterone levels. The latter clinical evidence confirms the presence of biological markers consistent with a broad range of inflammatory disorders, including both cardiovascular and autoimmune diseases.

The articulation of integration of clinical and basic sciences in concept maps: differences between experienced and resident groups.

PubMed

Vink, Sylvia; van Tartwijk, Jan; Verloop, Nico; Gosselink, Manon; Driessen, Erik; Bolk, Jan

2016-08-01

To determine the content of integrated curricula, clinical concepts and the underlying basic science concepts need to be made explicit. Preconstructed concept maps are recommended for this purpose. They are mainly constructed by experts. However, concept maps constructed by residents are hypothesized to be less complex, to reveal more tacit basic science concepts and these basic science concepts are expected to be used for the organization of the maps. These hypotheses are derived from studies about knowledge development of individuals. However, integrated curricula require a high degree of cooperation between clinicians and basic scientists. This study examined whether there are consistent variations regarding the articulation of integration when groups of experienced clinicians and basic scientists and groups of residents and basic scientists-in-training construct concept maps. Seven groups of three clinicians and basic scientists on experienced level and seven such groups on resident level constructed concept maps illuminating clinical problems. They were guided by instructions that focused them on articulation of integration. The concept maps were analysed by features that described integration. Descriptive statistics showed consistent variations between the two expertise levels. The concept maps of the resident groups exceeded those of the experienced groups in articulated integration. First, they used significantly more links between clinical and basic science concepts. Second, these links connected basic science concepts with a greater variety of clinical concepts than the experienced groups. Third, although residents did not use significantly more basic science concepts, they used them significantly more frequent to organize the clinical concepts. The conclusion was drawn that not all hypotheses could be confirmed and that the resident concept maps were more elaborate than expected. This article discusses the implications for the role that residents and basic scientists-in-training might play in the construction of preconstructed concept maps and the development of integrated curricula.

Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

2013-02-01

To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P< .001) and cortical presentations (P< .001); CASPR2 IgG was associated with peripheral motor excitability (P= .009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

PubMed Central

Klein, Christopher J.; Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; O’Toole, Orna; Quek, Amy; Pittock, Sean J.

2014-01-01

Objective: To determine, in patients identified as sero-positive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Design: Retrospective cohort study. Setting: Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. Patients: A total of 54853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. Results: From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54 853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P<.001) and cortical presentations (P<.001); CASPR2 IgG was associated with peripheral motor excitability (P=.009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. Conclusions: The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined. PMID:23407760

Comparing clinical and demographic characteristics of people with mental illness in hospital- and community-based residential rehabilitation units in Queensland.

PubMed

Meehan, Tom; Stedman, Terry; Parker, Stephen; Curtis, Bretine; Jones, Donna

2017-05-01

Objective The aim of the present study was to examine care pathways and characteristics of mental health consumers participating in both hospital- and community-based residential rehabilitation programs. Methods An audit of consumers (n=240) in all publicly funded residential rehabilitation units in Queensland was performed on the same day in 2013. Data collection focused on demographic characteristics, clinical information and measures of consumer functioning. Results Significant differences emerged for consumers in community- and hospital-based services with regard to age, length of stay, functioning, Mental Health Act status, guardianship status, family contact and risk of violence. Consumers in hospital-based programs have more severe and complex problems. Conclusions Consumers in residential rehabilitation units have high levels of disability, poor physical health and high levels of vulnerability. Nonetheless, it is likely that a sizeable proportion of consumers occupying rehabilitation beds in Queensland could be discharged if more 'step-down' options to move patients on were available. What is known about the topic? A small subgroup of people with severe and complex mental health problems is likely to require time in a residential rehabilitation program. This group is characterised by failure to respond to treatment, severe negative symptoms and some degree of cognitive impairment. What does this paper add? Patients currently occupying residential rehabilitation beds in Queensland have high levels of disability, poor physical health and high levels of vulnerability. Patients in hospital-based programs are more severely disabled than those in community-based programs. What are the implications for practitioners? It is likely that a sizeable proportion of patients occupying rehabilitation beds in Queensland could be discharged if more 'step-down' options were available. Future planning initiatives need to focus on developing a greater array of community support options to facilitate the discharge of people from residential services.

Actin-related protein 2/3 complex-based actin polymerization is critical for male fertility.

PubMed

Lee, J S; Kwon, W S; Rahman, M S; Yoon, S J; Park, Y J; Pang, M G

2015-09-01

The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of actin polymerization, which is associated with sperm motility and capacitation status. However, the function of the Arp2/3 complex in male fertility has not yet been fully elucidated. Therefore, this study was designed to investigate the role of the Arp2/3 complex in different processes in spermatozoa and its consequences on fertilization and early embryonic development. In this in vitro study, mouse spermatozoa were incubated with different concentrations (10, 100, and 500 μm) of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition of the Arp2/3 complex by high concentrations (100 and 500 μm) of CK-636 induced hyper-activated motility and acrosomal reaction, whereas intracellular calcium and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover, exposure of spermatozoa to the highest concentration of CK-636 reduced fertilization and embryo development. Interestingly, fertilization was significantly increased after treatment with 100 μm CK-636, whereas embryonic development was significantly decreased. Therefore, we conclude that the Arp2/3 complex plays a decisive role in regulation of sperm function and male fertility via actin polymerization. We anticipate that the Arp2/3 complex may have clinical application as marker for male fertility and male contraceptive targeting. © 2015 American Society of Andrology and European Academy of Andrology.

Assessing the Readability of Medical Documents: A Ranking Approach.

PubMed

Zheng, Jiaping; Yu, Hong

2018-03-23

The use of electronic health record (EHR) systems with patient engagement capabilities, including viewing, downloading, and transmitting health information, has recently grown tremendously. However, using these resources to engage patients in managing their own health remains challenging due to the complex and technical nature of the EHR narratives. Our objective was to develop a machine learning-based system to assess readability levels of complex documents such as EHR notes. We collected difficulty ratings of EHR notes and Wikipedia articles using crowdsourcing from 90 readers. We built a supervised model to assess readability based on relative orders of text difficulty using both surface text features and word embeddings. We evaluated system performance using the Kendall coefficient of concordance against human ratings. Our system achieved significantly higher concordance (.734) with human annotators than did a baseline using the Flesch-Kincaid Grade Level, a widely adopted readability formula (.531). The improvement was also consistent across different disease topics. This method's concordance with an individual human user's ratings was also higher than the concordance between different human annotators (.658). We explored methods to automatically assess the readability levels of clinical narratives. Our ranking-based system using simple textual features and easy-to-learn word embeddings outperformed a widely used readability formula. Our ranking-based method can predict relative difficulties of medical documents. It is not constrained to a predefined set of readability levels, a common design in many machine learning-based systems. Furthermore, the feature set does not rely on complex processing of the documents. One potential application of our readability ranking is personalization, allowing patients to better accommodate their own background knowledge. ©Jiaping Zheng, Hong Yu. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 23.03.2018.

The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators

PubMed Central

Johansson, Maria E.; Edström-Hägerwall, Anneli; Larsson, Irene; Jälmby, Maya; Hansson, Stefan R.; Åkerström, Bo

2015-01-01

Preeclampsia (PE) complicates 3–8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), α1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems. PMID:26368565

Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression.

PubMed

Mello-Andrade, Francyelli; da Costa, Wanderson Lucas; Pires, Wanessa Carvalho; Pereira, Flávia de Castro; Cardoso, Clever Gomes; Lino-Junior, Ruy de Souza; Irusta, Vicente Raul Chavarria; Carneiro, Cristiene Costa; de Melo-Reis, Paulo Roberto; Castro, Carlos Henrique; Almeida, Marcio Aurélio Pinheiro; Batista, Alzir Azevedo; Silveira-Lacerda, Elisângela de Paula

2017-10-01

Peritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited. The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF 6 (1) and the [Ru(l-Trp)(bipy)(dppb)]PF 6 (2) complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma-bearing Swiss mice. This is the first study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and 6 mg kg -1 ) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites carcinoma-bearing mice with complexes 1 and 2 increased the number of Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro-which suggests that the LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.

Clinical quality needs complex adaptive systems and machine learning.

PubMed

Marsland, Stephen; Buchan, Iain

2004-01-01

The vast increase in clinical data has the potential to bring about large improvements in clinical quality and other aspects of healthcare delivery. However, such benefits do not come without cost. The analysis of such large datasets, particularly where the data may have to be merged from several sources and may be noisy and incomplete, is a challenging task. Furthermore, the introduction of clinical changes is a cyclical task, meaning that the processes under examination operate in an environment that is not static. We suggest that traditional methods of analysis are unsuitable for the task, and identify complexity theory and machine learning as areas that have the potential to facilitate the examination of clinical quality. By its nature the field of complex adaptive systems deals with environments that change because of the interactions that have occurred in the past. We draw parallels between health informatics and bioinformatics, which has already started to successfully use machine learning methods.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

A diffusion of innovations model of physician order entry.

PubMed

Ash, J S; Lyman, J; Carpenter, J; Fournier, L

2001-01-01

To interpret the results of a cross-site study of physician order entry (POE) in hospitals using a diffusion of innovations theory framework. Qualitative study using observation, focus groups, and interviews. Data were analyzed by an interdisciplinary team of researchers using a grounded approach to identify themes. Themes were then interpreted using classical Diffusion of Innovations (DOI) theory as described by Rogers [1]. Four high level themes were identified: organizational issues; clinical and professional issues; technology implementation issues; and issues related to the organization of information and knowledge. Further analysis using the DOI framework indicated that POE is an especially complex information technology innovation when one considers communication, time, and social system issues in addition to attributes of the innovation itself. Implementation strategies for POE should be designed to account for its complex nature. The ideal would be a system that is both customizable and integrated with other parts of the information system, is implemented with maximum involvement of users and high levels of support, and is surrounded by an atmosphere of trust and collaboration.

42 CFR 493.1415 - Condition: Laboratories performing moderate complexity testing; clinical consultant.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Laboratories performing moderate complexity testing; clinical consultant. 493.1415 Section 493.1415 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION...

A systems approach to bone pathophysiology.

PubMed

Weiss, Aaron J; Lipshtat, Azi; Mechanick, Jeffrey I

2010-11-01

With evolving interest in multiscalar biological systems one could assume that reductionist approaches may not fully describe biological complexity. Instead, tools such as mathematical modeling, network analysis, and other multiplexed clinical- and research-oriented tests enable rapid analyses of high-throughput data parsed at the genomic, proteomic, metabolomic, and physiomic levels. A physiomic-level approach allows for recursive horizontal and vertical integration of subsystem coupling across and within spatiotemporal scales. Additionally, this methodology recognizes previously ignored subsystems and the strong, nonintuitively obvious and indirect connections among physiological events that potentially account for the uncertainties in medicine. In this review, we flip the reductionist research paradigm and review the concept of systems biology and its applications to bone pathophysiology. Specifically, a bone-centric physiome model is presented that incorporates systemic-level processes with their respective therapeutic implications. © 2010 New York Academy of Sciences.

Protein and peptide-based therapeutics in periodontal regeneration.

PubMed

Reynolds, Mark A; Aichelmann-Reidy, Mary E

2012-09-01

Protein and peptide-based therapeutics provide a unique strategy for controlling highly specific and complex biologic actions that cannot be accomplished by simple devices or chemical compounds. This article reviews some of the key characteristics and summarizes the clinical effectiveness of protein and peptide-based therapeutics targeting periodontal regeneration. A literature search was conducted of randomized clinical trials and systematic reviews evaluating protein and peptide-based therapeutics for the regeneration of periodontal tissues of at least 6 months duration. Data sources included PubMed and Embase electronic databases, hand-searched journals, and the ClinicalTrials.gov registry. Commercially marketed protein and peptide-based therapeutics for periodontal regeneration provide gains in clinical attachment level and bone formation that are comparable or superior to other regenerative approaches. Results from several clinical trials indicate that protein and peptide-based therapies can accelerate repair and regeneration when compared with other treatments and that improvements in clinical parameters continue beyond 12 months. Protein and peptide-based therapies also exhibit the capacity to increase the predictability of treatment outcomes. Clinical and histologic studies support the effectiveness of protein- and peptide-based therapeutics for periodontal regeneration. Emerging evidence suggests that the delivery devices/scaffolds play a critical role in determining the effectiveness of this class of therapeutics. Copyright © 2012 Elsevier Inc. All rights reserved.

Excellence in clinical teaching: knowledge transformation and development required.

PubMed

Irby, David M

2014-08-01

Clinical teachers in medicine face the daunting task of mastering the many domains of knowledge needed for practice and teaching. The breadth and complexity of this knowledge continue to increase, as does the difficulty of transforming the knowledge into concepts that are understandable to learners. Properly targeted faculty development has the potential to expedite the knowledge transformation process for clinical teachers. Based on my own research in clinical teaching and faculty development, as well as the work of others, I describe the unique forms of clinical teacher knowledge, the transformation of that knowledge for teaching purposes and implications for faculty development. The following forms of knowledge for clinical teaching in medicine need to be mastered and transformed: (i) knowledge of medicine and patients; (ii) knowledge of context; (iii) knowledge of pedagogy and learners, and (iv) knowledge integrated into teaching scripts. This knowledge is employed and conveyed through the parallel processes of clinical reasoning and clinical instructional reasoning. Faculty development can facilitate this knowledge transformation process by: (i) examining, deconstructing and practising new teaching scripts; (ii) focusing on foundational concepts; (iii) demonstrating knowledge-in-use, and (iv) creating a supportive organisational climate for clinical teaching. To become an excellent clinical teacher in medicine requires the transformation of multiple forms of knowledge for teaching purposes. These domains of knowledge allow clinical teachers to provide tailored instruction to learners at varying levels in the context of fast-paced and demanding clinical practice. Faculty development can facilitate this knowledge transformation process. © 2014 John Wiley & Sons Ltd.

The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines.

PubMed

Malhi, Gin S; Gessler, Danielle; Outhred, Tim

2017-08-01

Lithium is an effective mood stabilizer that is used principally for the management of bipolar disorder (BD). Its administration is complex and often requires sophisticated management and assiduous monitoring. When considering the use of lithium therapy for bipolar disorder, clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs); but because of varying emphases placed by different international CPGs, recommendations addressing the practical use of lithium lack consistency. In order to inform clinicians of optimal lithium therapy for bipolar disorder, we compared and synthesized recommendations for the treatment of bipolar disorder made by recognized CPGs internationally. We conducted a search of the literature and extracted guidance across multiple clinical issues, including clinical indications, disorder subtypes, additional uses, special populations, practical aspects, and side effects. Collectively, CPGs consider lithium most robustly as a first-line intervention for maintenance treatment of bipolar disorder and strongly for the treatment of mania, with relatively modest support for the management of acute bipolar depression. Additionally, there is consensus across the CPGs that lithium tangibly reduces the risk of suicide. Generally, CPGs provide guidance on the many facets of initiating and maintaining patients on lithium therapy, but individually the CPGs varied in terms of depth and practical guidance they provide across these areas. However, consensus was established across many key areas of practice such as the ideal lithium plasma concentration for maintenance and monitoring (0.6-0.8mmol/L), along with the need for regular monitoring of renal and endocrine function. However, with more complex aspects (e.g., atypical presentations) and in special populations (e.g., youth; pregnancy and post-partum; older adults), guidance varied considerably and clear consensus recommendations were more difficult to achieve. In younger adults desirable plasma lithium levels of 0.6-0.8mmol/L can perhaps be achieved with comparatively lower doses and in the very elderly it may be prudent to target lower plasma levels in the first instance. These are important practical points for consideration that, along with many others offered throughout the article, should assist clinicians in dissecting the more complex aspects of management with greater precision. This review was limited to CPGs written in English. CPGs are themselves limited by reliance on evidence that often has little resemblance to real-world presentations. An important area that is not sufficiently addressed in the CPGs is clear guidance on the cessation of lithium therapy. Further research is needed on many aspects of lithium therapy and this alongside existing knowledge needs to be used more consistently to inform CPGs, which should also incorporate empirical evidence and clinical experience. The recommendations in this paper provide a useful synthesis of guidance available currently. Copyright © 2017 Elsevier B.V. All rights reserved.

Pre- and postoperative evaluation of patients with lumbosacral disc herniation by neurophysiological and clinical assessment.

PubMed

Wojtysiak, Magdalena; Huber, Juliusz; Wiertel-Krawczuk, Agnieszka; Szymankiewicz-Szukała, Agnieszka; Moskal, Jakub; Janicki, Jacek

2014-10-01

The application of complex neurophysiological examination including motor evoked potentials (MEP) for pre- and postoperative evaluation of patients experiencing acute sciatica. The assessment of sensitivity and specificity of needle electromyography, MEP, and H-reflex examinations. The comparative analysis of preoperative and postoperative neurophysiological examination. In spite of the fact that complex neurophysiological diagnostic tools seem to be important for interpretation of incompatible results of neuroimaging and clinical examination, especially in the patients qualified for surgical treatment, their application has never been completely analyzed and documented. Pre- and postoperative electromyography, electroneurography, F-waves, H-reflex, and MEP examination were performed in 23 patients with confirmed disc-root conflict at lumbosacral spine. Clinical evaluation included examination of sensory perception for L5-S1 dermatomes, muscles strength with Lovett's scale, deep tendon reflexes, pain intensity with visual analogue scale, and straight leg raising test. Sensitivity of electromyography at rest and MEP examination for evaluation of L5-S1 roots injury was 22% to 63% and 31% to 56% whereas specificity was 71% to 83% and 57% to 86%, respectively. H-reflex sensitivity and specificity for evaluation of S1 root injury were 56% and 67%, respectively. A significant improvement of root latency parameter in postoperative MEP studies as compared with preoperative was recorded for L5 (P = 0.039) and S1 root's levels (P = 0.05). The analysis of the results from neurophysiological tests together with neuroimaging and clinical examination allow for a precise preoperative indication of the lumbosacral roots injury and accurate postoperative evaluation of patients experiencing sciatica. 3.

[Clinical practice guidelines for systemic lupus erythematosus: Recommendations for general clinical management].

PubMed

Trujillo-Martín, María M; Rúa-Figueroa Fernández de Larrinoa, Iñigo; Ruíz-Irastorza, Guillermo; Pego-Reigosa, José María; Sabio Sánchez, José Mario; Serrano-Aguilar, Pedro

2016-05-06

Systemic lupus erythematosus (SLE) is a complex rheumatic multisystemic disease of autoimmune origin with significant potential morbidity and mortality. It is one of the most common autoimmune diseases with an estimated prevalence of 20-150 cases per 100,000 inhabitants. The clinical spectrum of SLE is wide and variable both in clinical manifestations and severity. This prompted the Spanish Ministry of Health, Social Services and Equality to promote and fund the development of a clinical practice guideline (CPG) for the clinical care of SLE patients within the Programme of CPG in the National Health System which coordinates GuiaSalud. This CPG is is intended as the reference tool in the Spanish National Health System in order to support the comprehensive clinical management of people with SLE by all health professionals involved, regardless of specialty and level of care, helping to standardize and improve the quality of clinical decisions in our context in order to improve the health outcomes of the people affected. The purpose of this document is to present and discuss the rationale of the recommendations on the general management of SLE, specifically, clinical follow-up, general therapeutic approach, healthy lifestyles, photoprotection, and training programmes for patients. These recommendations are based on the best available scientific evidence, on discussion and the consensus of expert groups. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

A personal reflection on social media in medicine: I stand, no wiser than before.

PubMed

Weiner, John

2015-04-01

Social media has enabled information, communication and reach for health professionals. There are clear benefits to patients and consumers when health information is broadcast. But there are unanswered questions on professionalism, education, and the complex mentoring relationship between doctor and student. This personal perspective raises a number of questions: What is online medical professionalism? Can online medical professionalism be taught? Can online medical professionalism be enforced? Is an online presence necessary to achieve the highest level of clinical excellence? Is there evidence that social media is superior to traditional methods of teaching in medical education? Does social media encourage multitasking and impairment of the learning process? Are there downsides to the perfunctory laconic nature of social media? Does social media waste time that is better spent attaining clinical skills?

Professional socialization of students in clinical nurse specialist programs.

PubMed

Ares, Terri L

2014-11-01

Graduate nursing programs facilitate the transition of RNs to advanced roles through a complex process of professional socialization. The purpose of this study was to explore the professional socialization of clinical nurse specialist (CNS) students. Two hundred twenty-five students, representing 73 CNS programs, responded to an online survey. Both preprogram variables and educational experiences contributed to an adequate level of CNS socialization. Students' self-concept was strong, and they felt prepared to practice in the role, which was highly correlated with their perceptions of how well the program prepared them academically and experientially. Having a CNS mentor was positively associated with readiness to practice. Outcomes did not vary with cohort status, and online instruction did not impede socialization. These findings provide implications for CNS program advisement and design. Copyright 2014, SLACK Incorporated.

In the margins of the mind: development of a projective research methodology for the study of nursing practice.

PubMed

Regan, Mary; Liaschenko, Joan

2008-01-01

This article presents an original research method derived from the Thematic Apperception Test used in clinical psychology to understand human motivation and action. The research method is derived from the theory of projection, which states that humans will perceive stimuli in terms of their own expectations and motives and will credit others with their own attitudes, beliefs, traits, and dispositions. Projective techniques are one of a handful of methods that provide access to this type of knowledge since it resides below the level of consciousness. Use of this type of method in nursing research may be fruitful because of its capacity to make apparent the complex interplay between a clinician's beliefs and the interpretation of meaning that motivates clinical action.

A Hybrid Methodology for Modeling Risk of Adverse Events in Complex Health-Care Settings.

PubMed

Kazemi, Reza; Mosleh, Ali; Dierks, Meghan

2017-03-01

In spite of increased attention to quality and efforts to provide safe medical care, adverse events (AEs) are still frequent in clinical practice. Reports from various sources indicate that a substantial number of hospitalized patients suffer treatment-caused injuries while in the hospital. While risk cannot be entirely eliminated from health-care activities, an important goal is to develop effective and durable mitigation strategies to render the system "safer." In order to do this, though, we must develop models that comprehensively and realistically characterize the risk. In the health-care domain, this can be extremely challenging due to the wide variability in the way that health-care processes and interventions are executed and also due to the dynamic nature of risk in this particular domain. In this study, we have developed a generic methodology for evaluating dynamic changes in AE risk in acute care hospitals as a function of organizational and nonorganizational factors, using a combination of modeling formalisms. First, a system dynamics (SD) framework is used to demonstrate how organizational-level and policy-level contributions to risk evolve over time, and how policies and decisions may affect the general system-level contribution to AE risk. It also captures the feedback of organizational factors and decisions over time and the nonlinearities in these feedback effects. SD is a popular approach to understanding the behavior of complex social and economic systems. It is a simulation-based, differential equation modeling tool that is widely used in situations where the formal model is complex and an analytical solution is very difficult to obtain. Second, a Bayesian belief network (BBN) framework is used to represent patient-level factors and also physician-level decisions and factors in the management of an individual patient, which contribute to the risk of hospital-acquired AE. BBNs are networks of probabilities that can capture probabilistic relations between variables and contain historical information about their relationship, and are powerful tools for modeling causes and effects in many domains. The model is intended to support hospital decisions with regard to staffing, length of stay, and investments in safety, which evolve dynamically over time. The methodology has been applied in modeling the two types of common AEs: pressure ulcers and vascular-catheter-associated infection, and the models have been validated with eight years of clinical data and use of expert opinion. © 2017 Society for Risk Analysis.

Clinical Uncertainties, Health Service Challenges, and Ethical Complexities of HIV “Test-and-Treat”: A Systematic Review

PubMed Central

Shah, Kavita R.; Sarma, Karthik V.; Mahajan, Anish P.

2013-01-01

Despite the HIV “test-and-treat” strategy’s promise, questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous debate in the global HIV community. We performed a systematic review of the literature published between January 2009 and May 2012 using PubMed, SCOPUS, Global Health, Web of Science, BIOSIS, Cochrane CENTRAL, EBSCO Africa-Wide Information, and EBSCO CINAHL Plus databases to summarize clinical uncertainties, health service challenges, and ethical complexities that may affect the test-and-treat strategy’s success. A thoughtful approach to research and implementation to address clinical and health service questions and meaningful community engagement regarding ethical complexities may bring us closer to safe, feasible, and effective test-and-treat implementation. PMID:23597344