The antigenic evolution of influenza: drift or thrift?

PubMed Central

Wikramaratna, Paul S.; Sandeman, Michi; Recker, Mario; Gupta, Sunetra

2013-01-01

It is commonly assumed that antibody responses against the influenza virus are polarized in the following manner: strong antibody responses are directed at highly variable antigenic epitopes, which consequently undergo ‘antigenic drift’, while weak antibody responses develop against conserved epitopes. As the highly variable epitopes are in a constant state of flux, current antibody-based vaccine strategies are focused on the conserved epitopes in the expectation that they will provide some level of clinical protection after appropriate boosting. Here, we use a theoretical model to suggest the existence of epitopes of low variability, which elicit a high degree of both clinical and transmission-blocking immunity. We show that several epidemiological features of influenza and its serological and molecular profiles are consistent with this model of ‘antigenic thrift’, and that identifying the protective epitopes of low variability predicted by this model could offer a more viable alternative to regularly update the influenza vaccine than exploiting responses to weakly immunogenic conserved regions. PMID:23382423

High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients

PubMed Central

Goodall, Dawn L.; Willicombe, Michelle; McLean, Adam G.; Taube, David

2017-01-01

Background Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol. Methods We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance. Results Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005). Conclusions This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes. PMID:28795143

A diagnostic model for chronic hypersensitivity pneumonitis.

PubMed

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2016-10-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. 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/

Service and Education: The Association Between Workload, Patient Complexity, and Teaching on Internal Medicine Inpatient Services.

PubMed

Ratcliffe, Temple A; Crabtree, Meghan A; Palmer, Raymond F; Pugh, Jacqueline A; Lanham, Holly J; Leykum, Luci K

2018-04-01

Attending rounds remain the primary venue for formal teaching and learning at academic medical centers. Little is known about the effect of increasing clinical demands on teaching during attending rounds. To explore the relationships among teaching time, teaching topics, clinical workload, and patient complexity variables. Observational study of medicine teaching teams from September 2008 through August 2014. Teams at two large teaching hospitals associated with a single medical school were observed for periods of 2 to 4 weeks. Twelve medicine teaching teams consisting of one attending, one second- or third-year resident, two to three interns, and two to three medical students. The study examined relationships between patient complexity (comorbidities, complications) and clinical workload variables (census, turnover) with educational measures. Teams were clustered based on clinical workload and patient complexity. Educational measures of interest were time spent teaching and number of teaching topics. Data were analyzed both at the daily observation level and across a given patient's admission. We observed 12 teams, 1994 discussions (approximately 373 h of rounds) of 563 patients over 244 observation days. Teams clustered into three groups: low patient complexity/high clinical workload, average patient complexity/low clinical workload, and high patient complexity/high clinical workload. Modest associations for team, patient complexity, and clinical workload variables were noted with total time spent teaching (9.1% of the variance in time spent teaching during a patient's admission; F[8,549] = 6.90, p < 0.001) and number of teaching topics (16% of the variance in the total number of teaching topics during a patient's admission; F[8,548] = 14.18, p < 0.001). Clinical workload and patient complexity characteristics among teams were only modestly associated with total teaching time and teaching topics.

Symbolic dynamics marker of heart rate variability combined with clinical variables enhance obstructive sleep apnea screening

NASA Astrophysics Data System (ADS)

Ravelo-García, A. G.; Saavedra-Santana, P.; Juliá-Serdá, G.; Navarro-Mesa, J. L.; Navarro-Esteva, J.; Álvarez-López, X.; Gapelyuk, A.; Penzel, T.; Wessel, N.

2014-06-01

Many sleep centres try to perform a reduced portable test in order to decrease the number of overnight polysomnographies that are expensive, time-consuming, and disturbing. With some limitations, heart rate variability (HRV) has been useful in this task. The aim of this investigation was to evaluate if inclusion of symbolic dynamics variables to a logistic regression model integrating clinical and physical variables, can improve the detection of subjects for further polysomnographies. To our knowledge, this is the first contribution that innovates in that strategy. A group of 133 patients has been referred to the sleep center for suspected sleep apnea. Clinical assessment of the patients consisted of a sleep related questionnaire and a physical examination. The clinical variables related to apnea and selected in the statistical model were age (p < 10-3), neck circumference (p < 10-3), score on a questionnaire scale intended to quantify daytime sleepiness (p < 10-3), and intensity of snoring (p < 10-3). The validation of this model demonstrated an increase in classification performance when a variable based on non-linear dynamics of HRV (p < 0.01) was used additionally to the other variables. For diagnostic rule based only on clinical and physical variables, the corresponding area under the receiver operating characteristic (ROC) curve was 0.907 (95% confidence interval (CI) = 0.848, 0.967), (sensitivity 87.10% and specificity 80%). For the model including the average of a symbolic dynamic variable, the area under the ROC curve was increased to 0.941 (95% = 0.897, 0.985), (sensitivity 88.71% and specificity 82.86%). In conclusion, symbolic dynamics, coupled with significant clinical and physical variables can help to prioritize polysomnographies in patients with a high probability of apnea. In addition, the processing of the HRV is a well established low cost and robust technique.

Patient-Centered Research

PubMed Central

Wicki, J; Perneger, TV; Junod, AF; Bounameaux, H; Perrier, A

2000-01-01

PURPOSE We aimed to develop a simple standardized clinical score to stratify emergency ward patients with clinically suspected PE into groups with a high, intermediate, or low probability of PE, in order to improve and simplify the diagnostic approach. METHODS Analysis of a database of 1090 consecutive patients admitted to the emergency ward for suspected PE, in whom diagnosis of PE was ruled in or out by a standard diagnostic algorithm. Logistic regression was used to predict clinical parameters associated with PE. RESULTS 296 out of 1090 patients (27%) were found to have PE. The optimal estimate of clinical probability was based on eight variables: recent surgery, previous thromboembolic event, older age, hypocapnia, hypoxemia, tachycardia, band atelectasis or elevation of a hemidiaphragm on chest X-ray. A probability score was calculated by adding points assigned to these variables. A cut-off score of 4 best identified patients with low probability of PE. 486 patients (49%) had a low clinical probability of PE (score < 4), of which 50 (10.3%) had a proven PE. The prevalence of PE was 38% in the 437 patients with an intermediate probability (score 5–8, n = 437) and 81% in the 63 patients with a high probability (score>9). CONCLUSION This clinical score, based on easily available and objective variables, provides a standardized assessment of the clinical probability of PE. Applying this score to emergency ward patients suspected of PE could allow a more efficient diagnostic process.

Improved modeling of clinical data with kernel methods.

PubMed

Daemen, Anneleen; Timmerman, Dirk; Van den Bosch, Thierry; Bottomley, Cecilia; Kirk, Emma; Van Holsbeke, Caroline; Valentin, Lil; Bourne, Tom; De Moor, Bart

2012-02-01

Despite the rise of high-throughput technologies, clinical data such as age, gender and medical history guide clinical management for most diseases and examinations. To improve clinical management, available patient information should be fully exploited. This requires appropriate modeling of relevant parameters. When kernel methods are used, traditional kernel functions such as the linear kernel are often applied to the set of clinical parameters. These kernel functions, however, have their disadvantages due to the specific characteristics of clinical data, being a mix of variable types with each variable its own range. We propose a new kernel function specifically adapted to the characteristics of clinical data. The clinical kernel function provides a better representation of patients' similarity by equalizing the influence of all variables and taking into account the range r of the variables. Moreover, it is robust with respect to changes in r. Incorporated in a least squares support vector machine, the new kernel function results in significantly improved diagnosis, prognosis and prediction of therapy response. This is illustrated on four clinical data sets within gynecology, with an average increase in test area under the ROC curve (AUC) of 0.023, 0.021, 0.122 and 0.019, respectively. Moreover, when combining clinical parameters and expression data in three case studies on breast cancer, results improved overall with use of the new kernel function and when considering both data types in a weighted fashion, with a larger weight assigned to the clinical parameters. The increase in AUC with respect to a standard kernel function and/or unweighted data combination was maximum 0.127, 0.042 and 0.118 for the three case studies. For clinical data consisting of variables of different types, the proposed kernel function--which takes into account the type and range of each variable--has shown to be a better alternative for linear and non-linear classification problems. Copyright © 2011 Elsevier B.V. All rights reserved.

Exploring heterogeneity in clinical trials with latent class analysis

PubMed Central

Abarda, Abdallah; Contractor, Ateka A.; Wang, Juan; Dayton, C. Mitchell

2018-01-01

Case-mix is common in clinical trials and treatment effect can vary across different subgroups. Conventionally, a subgroup analysis is performed by dividing the overall study population by one or two grouping variables. It is usually impossible to explore complex high-order intersections among confounding variables. Latent class analysis (LCA) provides a framework to identify latent classes by observed manifest variables. Distal clinical outcomes and treatment effect can be different across these classes. This paper provides a step-by-step tutorial on how to perform LCA with R. A simulated dataset is generated to illustrate the process. In the example, the classify-analyze approach is employed to explore the differential treatment effects on distal outcomes across latent classes. PMID:29955579

Why aren’t they happy? An analysis of end-user satisfaction with Electronic health records

PubMed Central

Unni, Prasad; Staes, Catherine; Weeks, Howard; Kramer, Heidi; Borbolla, Damion; Slager, Stacey; Taft, Teresa; Chidambaram, Valliammai; Weir, Charlene

2016-01-01

Introduction. Implementations of electronic health records (EHR) have been met with mixed outcome reviews. Complaints about these systems have led to many attempts to have useful measures of end-user satisfaction. However, most user satisfaction assessments do not focus on high-level reasoning, despite the complaints of many physicians. Our study attempts to identify some of these determinants. Method. We developed a user satisfaction survey instrument, based on pre-identified and important clinical and non-clinical clinician tasks. We surveyed a sample of in-patient physicians and focused on using exploratory factor analyses to identify underlying high-level cognitive tasks. We used the results to create unique, orthogonal variables representative of latent structure predictive of user satisfaction. Results. Our findings identified 3 latent high-level tasks that were associated with end-user satisfaction: a) High- level clinical reasoning b) Communicate/coordinate care and c) Follow the rules/compliance. Conclusion: We were able to successfully identify latent variables associated with satisfaction. Identification of communicability and high-level clinical reasoning as important factors determining user satisfaction can lead to development and design of more usable electronic health records with higher user satisfaction. PMID:28269962

A comparison of technologies used for estimation of body temperature.

PubMed

Mangat, Jasdip; Standley, Thomas; Prevost, Andrew; Vasconcelos, Joana; White, Paul

2010-09-01

Body temperature measurement is an important clinical parameter. The performance of a number of non-invasive thermometers was measured by comparing intra- and inter-operator variability (n = 100) and clinical accuracy (n = 61). Variability was elevated in febrile compared to normothermic subjects for axillary and oral electronic contact thermometer measures and a temporal artery thermometer (p < 0.001 for both). Temporal artery thermometry and one mode of an infrared tympanic thermometer demonstrated significant clinical inaccuracy (p < 0.001 for both). Electronic contact thermometer repeatability and reproducibility are highly variable in febrile adults both in the axilla and oral cavity. Infrared thermometry of the skin over the superficial temporal artery is unreliable for measuring core body temperature, particularly in febrile subjects and patients in theatre. The infrared tympanic thermometers tested are acceptable for clinical practice; however, care should be exercised with the different modes of operation offered.

Personality-based subtypes of anorexia nervosa: examining validity and utility using baseline clinical variables and ecological momentary assessment.

PubMed

Lavender, Jason M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Crow, Scott J; Peterson, Carol B; Le Grange, Daniel

2013-08-01

This study sought to empirically derive and validate clinically relevant personality-based subtypes of anorexia nervosa (AN). Women (N = 116) with full or subthreshold AN completed baseline measures of personality, clinical variables, and eating disorder (ED) symptoms, followed by two weeks of ecological momentary assessment (EMA). A latent profile analysis was conducted to identify personality subtypes, which were compared on baseline clinical variables and EMA variables. The best-fitting model supported three subtypes: underregulated, overregulated, and low psychopathology. The underregulated subtype (characterized by high Stimulus Seeking, Self-Harm, and Oppositionality) displayed greater baseline ED symptoms, as well as lower positive affect and greater negative affect, self-discrepancy, and binge eating in the natural environment. The overregulated subtype (characterized by high Compulsivity and low Stimulus Seeking) was more likely to have a lifetime obsessive-compulsive disorder diagnosis and exhibited greater perfectionism; levels of negative affect, positive affect, and self-discrepancy in this group were intermediate between the other subtypes. The low psychopathology subtype (characterized by normative personality) displayed the lowest levels of baseline ED symptoms, co-occurring disorders, and ED behaviors measured via EMA. Findings support the validity of these personality-based subtypes, suggesting the potential utility of addressing within-diagnosis heterogeneity in the treatment of AN. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Does the Youth Psychopathic Traits Inventory (YPI) identify a clinically relevant subgroup among young offenders?].

PubMed

Mingers, Daniel; Köhler, Denis; Huchzermeier, Christian; Hinrichs, Günter

2017-01-01

Does the Youth Psychopathic Traits Inventory identify one or more high-risk subgroups among young offenders? Which recommendations for possible courses of action can be derived for individual clinical or forensic cases? Method: Model-based cluster analysis (Raftery, 1995) was conducted on a sample of young offenders (N = 445, age 14–22 years, M = 18.5, SD = 1.65). The resulting model was then tested for differences between clusters with relevant context variables of psychopathy. The variables included measures of intelligence, social competence, drug use, and antisocial behavior. Results: Three clusters were found (Low Trait, Impulsive/Irresponsible, Psychopathy) that differ highly significantly concerning YPI scores and the variables mentioned above. The YPI Scores Δ Low = 4.28 (Low Trait – Impulsive/Irresponsible) and Δ High = 6.86 (Impulsive/Irresponsible – Psychopathy) were determined to be thresholds between the clusters. The allocation of a person to be assessed within the calculated clusters allows for an orientation of consequent tests beyond the diagnosis of psychopathy. We conclude that the YPI is a valuable instrument for the assessment of young offenders, as it yields clinically and forensically relevant information concerning the cause and expected development of psychopathological behavior.

Recent developments in clopidogrel pharmacology and their relation to clinical outcomes.

PubMed

Gurbel, Paul A; Antonino, Mark J; Tantry, Udaya S

2009-08-01

Oral antiplatelet therapy with clopidogrel and aspirin is an important and widely prescribed strategy to prevent ischemic events in patients with cardiovascular diseases. However, the occurrence of thrombotic events including stent thrombosis is still high (> 10%). Current practice guidelines are mainly based on large-scale trials focusing on clinical endpoints and 'one size fits all' strategies of treating all patients with the same clopidogrel doses. Pharmacodynamic studies have demonstrated that the latter strategy is associated with wide response variability where a substantial percentage of patients show nonresponsivenes. Translational research studies have established the relation between clopidogrel nonresponsivenes or high on-treatment platelet reactivity to adverse clinical events, thereby establishing clopidogrel nonresponsivenes as an important emerging clinical entity. Clopidogrel response variability is primarily a pharmacokinetic phenomenon associated with insufficient active metabolite generation that is secondary to i) limited intestinal absorption affected by an ABCB1 gene polymorphism; ii) functional variability in P450 isoenzyme activity; and iii) a genetic polymorphism of CYP450 isoenzymes. Personalized antiplatelet treatment with higher clopidogrel doses in selected patients or with newer more potent P2Y(12) receptor blockers based on individual platelet function measurement can overcome some of the limitations of current clopidogrel treatment.

Characteristics of dental clinics in US children's hospitals.

PubMed

Ciesla, David; Kerins, Carolyn A; Seale, N Sue; Casamassimo, Paul S

2011-01-01

This study's purpose was to describe the workforce, patient, and service characteristics of dental clinics affiliated with US children's hospitals belonging to the National Association of Children's Hospital and Related Institutions (NACHRI). A 2-stage survey mechanism using ad hoc questionnaires sought responses from hospital administrators and dental clinic administrators. Questionnaires asked about: (1) clinic purpose; (2) workforce; (3) patient population; (4) dental services provided; (5) community professional relations; and (5) relationships with medical services. Of the 222 NACHRI-affiliated hospitals, 87 reported comprehensive dental clinics (CDCs) and 64 (74%) of CDCs provided data. Provision of tertiary medical services was significantly related to presence of a CDC. Most CDCs were clustered east of the Mississippi River. Size, workload, and patient characteristics were variable across CDCs. Most were not profitable. Medical diagnosis was the primary criterion for eligibility, with all but 1 clinic treating special needs children. Most clinics (74%) had dental residencies. Over 75% reported providing dental care prior to major medical care (cardiac, oncology, transplantation), but follow-up care was variable. Many children's hospitals reported comprehensive dental clinics, but the characteristics were highly variable, suggesting this element of the pediatric oral health care safety net may be fragile.

Changes in patellofemoral alignment do not cause clinical impact after open-wedge high tibial osteotomy.

PubMed

Lee, Yong Seuk; Lee, Sang Bok; Oh, Won Seok; Kwon, Yong Eok; Lee, Beom Koo

2016-01-01

The objectives of this study were (1) to evaluate the clinical and radiologic outcomes of open-wedge high tibial osteotomy focusing on patellofemoral alignment and (2) to search for correlation between variables and patellofemoral malalignment. A total of 46 knees (46 patients) from 32 females and 14 males who underwent open-wedge high tibial osteotomy were included in this retrospective case series. Outcomes were evaluated using clinical scales and radiologic parameters at the last follow-up. Pre-operative and final follow-up values were compared for the outcome analysis. For the focused analysis of the patellofemoral joint, correlation analyses between patellofemoral variables and pre- and post-operative weight-bearing line (WBL), clinical score, posterior slope, Blackburn Peel ratio, lateral patellar tilt, lateral patellar shift, and congruence angle were performed. The minimum follow-up period was 2 years and median follow-up period was 44 months (range 24-88 months). The percentage of weight-bearing line was shifted from 17.2 ± 11.1 to 56.7 ± 12.7%, and it was statistically significant (p < 0.01). Regarding the clinical results, statistical significance was observed using all scores (p < 0.01). In the radiologic evaluation, patellar descent was observed with statistical significance (p < 0.01). Last follow-up lateral patellar tilt was decreased with statistical significance (p < 0.01). In correlation analysis between variables of patellofemoral malalignment, the pre-operative weight-bearing line showed an association with the change in lateral patellar tilt and lateral patellar shift (correlation coefficient: 0.3). After open-wedge high tibial osteotomy, clinical results showed improvement, compared to pre-operative values. The patellar tilt and lateral patellar shift were not changed; however, descent of the patella was observed. Therefore, mild patellofemoral problems should not be a contraindication of the open-wedge high tibial osteotomy. Case series, Level IV.

Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high-sensitivity immunoassays.

PubMed

Winter, Randolph L; Saunders, Ashley B; Gordon, Sonya G; Miller, Matthew W; Fosgate, Geoffrey T; Suchodolski, Jan S; Steiner, Jörg M

2017-06-01

Biologic variability (BV) is one aspect of interpreting changes in biomarker concentrations known to be clinically important in people with cardiac disease, but it has not been adequately addressed in dogs so far. The purpose of the study was to determine BV of cardiac troponin I (cTnI) in healthy dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD). Healthy dogs and dogs with 3 stages of MMVD were prospectively assigned to groups based on comprehensive clinical evaluation using current guidelines. Concentrations of cTnI were measured hourly, daily, and weekly using standard and high-sensitivity immunoassays. Within- (CV I ) and between-subject (CV G ) coefficients of variability, percent reference change value (RCV), and index of individuality (IoI) were calculated. All 10 healthy dogs and 76/112 (68%) of samples from 28 MMVD dogs had cTnI concentrations below the limit of detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of healthy dog samples and no MMVD samples had cTnI below the high-sensitivity immunoassay LOD. Data analysis for the high-sensitivity immunoassay revealed CV I of 48.1%, CV G of 60.1%, RCV of 134.0%, and IoI of 0.804 in healthy dogs. In MMVD dogs, CV I was 39.6%, CV G was 80.7%, RCV was 110%, and IoI was 0.494. Of all MMVD dogs, those with Stage B2 had the lowest RCV of 91%. Biologic variability affects cTnI concentrations in healthy dogs and dogs with MMVD. Consideration of BV may be clinically relevant when monitoring individual changes in cTnI values, using high-sensitivity immunoassays. © 2017 American Society for Veterinary Clinical Pathology.

Clinical periodontal variables in patients with and without dementia-a systematic review and meta-analysis.

PubMed

Maldonado, Alejandra; Laugisch, Oliver; Bürgin, Walter; Sculean, Anton; Eick, Sigrun

2018-06-22

Considering the increasing number of elderly people, dementia has gained an important role in today's society. Although the contributing factors for dementia have not been fully understood, chronic periodontitis (CP) seems to have a possible link to dementia. To conduct a systematic review including meta-analysis in order to assess potential differences in clinical periodontal variables between patients with dementia and non-demented individuals. The following focused question was evaluated: is periodontitis associated with dementia? Electronic searches in two databases, MEDLINE and EMBASE, were conducted. Meta-analysis was performed with the collected data in order to find a statistically significant difference in clinical periodontal variables between the group of dementia and the cognitive normal controls. Forty-two articles remained for full text reading. Finally, seven articles met the inclusion criteria and only five studies provided data suitable for meta-analysis. Periodontal probing depth (PPD), bleeding on probing (BOP), gingival bleeding index (GBI), clinical attachment level (CAL), and plaque index (PI) were included as periodontal variables in the meta-analysis. Each variable revealed a statistically significant difference between the groups. In an attempt to reveal an overall difference between the periodontal variables in dementia patients and non-demented individuals, the chosen variables were transformed into units that resulted in a statistically significant overall difference (p < 0.00001). The current findings indicate that compared to systemically healthy individuals, demented patients show significantly worse clinical periodontal variables. However, further epidemiological studies including a high numbers of participants, the use of exact definitions both for dementia and chronic periodontitis and adjusted for cofounders is warranted. These findings appear to support the putative link between CP and dementia. Consequently, the need for periodontal screening and treatment of elderly demented people should be emphasized.

Impact of advanced monitoring variables on intraoperative clinical decision-making: an international survey.

PubMed

Joosten, Alexandre; Desebbe, Olivier; Suehiro, Koichi; Essiet, Mfonobong; Alexander, Brenton; Ricks, Cameron; Rinehart, Joseph; Faraoni, David; Cecconi, Maurizio; Van der Linden, Philippe; Cannesson, Maxime

2017-02-01

To assess the relationship between the addition of advanced monitoring variables and changes in clinical decision-making. A 15-questions survey was anonymously emailed to international experts and physician members of five anesthesia societies which focused on assessing treatment decisions of clinicians during three realistic clinical scenarios measured at two distinct time points. The first is when typical case information and basic monitoring (T1) were provided, and then once again after the addition of advanced monitoring variables (T2). We hypothesized that the addition of advanced variables would increase the incidence of an optimal therapeutic decision (a priori defined as the answer with the highest percentage of expert agreement) and decrease the variability among the physician's suggested treatments. The survey was completed by 18 experts and 839 physicians. Overall, adding advanced monitoring did not significantly increase physician response accuracy, with the least substantial changes noted on questions related to volume expansion or vasopressor administration. Moreover, advanced monitoring data did not significantly decrease the high level of initial practice variability in physician suggested treatments (P = 0.13), in contrast to the low variability observed within the expert group (P = 0.039). Additionally, 5-10 years of practice (P < 0.0001) and a cardiovascular subspecialty (P = 0.048) were both physician characteristics associated with a higher rate of optimal therapeutic decisions. The addition of advanced variables was of limited benefit for most physicians, further indicating the need for more in depth education on the clinical value and technical understanding of such variables.

Internalized stigma and its psychosocial correlates in Korean patients with serious mental illness.

PubMed

Kim, Woo Jung; Song, Youn Joo; Ryu, Hyun-Sook; Ryu, Vin; Kim, Jae Min; Ha, Ra Yeon; Lee, Su Jin; Namkoong, Kee; Ha, Kyooseob; Cho, Hyun-Sang

2015-02-28

We aimed to examine internalized stigma of patients with mental illness in Korea and identify the contributing factors to internalized stigma among socio-demographic, clinical, and psychosocial variables using a cross-sectional study design. A total of 160 patients were recruited from a university mental hospital. We collected socio-demographic data, clinical variables and administered self-report scales to measure internalized stigma and levels of self-esteem, hopelessness, social support, and social conflict. Internalized stigma was identified in 8.1% of patients in our sample. High internalized stigma was independently predicted by low self-esteem, high hopelessness, and high social conflict among the psychosocial variables. Our finding suggests that simple psychoeducation only for insight gaining cannot improve internalized stigma. To manage internalized stigma in mentally ill patients, it is needed to promote hope and self-esteem. We also suggest that a relevant psychosocial intervention, such as developing coping skills for social conflict with family, can help patients overcome their internalized stigma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Variability in objective and subjective measures affects baseline values in studies of patients with COPD

PubMed Central

Ha, Jae Wook; Couper, David J.; O’Neal, Wanda K.; Barr, R. Graham; Bleecker, Eugene R.; Carretta, Elizabeth E.; Cooper, Christopher B.; Doerschuk, Claire M.; Drummond, M Bradley; Han, MeiLan K.; Hansel, Nadia N.; Kim, Victor; Kleerup, Eric C.; Martinez, Fernando J.; Rennard, Stephen I.; Tashkin, Donald; Woodruff, Prescott G.; Paine, Robert; Curtis, Jeffrey L.; Kanner, Richard E.

2017-01-01

Rationale Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety. Objectives Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes. Methods Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same period. We utilized SPIROMICS participants (n = 98) that returned to their clinical center within 6 weeks of their baseline visit to repeat complete baseline assessments. Demographics, spirometry, questionnaires, complete blood cell counts (CBC), medical history, and emphysema status by computerized tomography (CT) imaging were obtained. Results Pulmonary function tests (PFTs) were highly repeatable (ICC’s >0.9) but the 6 minute walk (6MW) was less so (ICC = 0.79). Among questionnaires, the Saint George’s Respiratory Questionnaire (SGRQ) was most repeatable. Self-reported clinical features, such as exacerbation history, and features of chronic bronchitis, often produced kappa values <0.6. Reported age at starting smoking and average number of cigarettes smoked were modestly repeatable (kappa = 0.76 and 0.79). Complete blood counts (CBC) variables produced intraclass correlation coefficients (ICC) values between 0.6 and 0.8. Conclusions PFTs were highly repeatable, while subjective measures and subject recall were more variable. Analyses using features with poor repeatability could lead to misclassification and outcome errors. Hence, care should be taken when interpreting change in clinical features based on measures with low repeatability. Efforts to improve repeatability of key clinical features such as exacerbation history and chronic bronchitis are warranted. PMID:28934249

Low-Dimensional Statistics of Anatomical Variability via Compact Representation of Image Deformations.

PubMed

Zhang, Miaomiao; Wells, William M; Golland, Polina

2016-10-01

Using image-based descriptors to investigate clinical hypotheses and therapeutic implications is challenging due to the notorious "curse of dimensionality" coupled with a small sample size. In this paper, we present a low-dimensional analysis of anatomical shape variability in the space of diffeomorphisms and demonstrate its benefits for clinical studies. To combat the high dimensionality of the deformation descriptors, we develop a probabilistic model of principal geodesic analysis in a bandlimited low-dimensional space that still captures the underlying variability of image data. We demonstrate the performance of our model on a set of 3D brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our model yields a more compact representation of group variation at substantially lower computational cost than models based on the high-dimensional state-of-the-art approaches such as tangent space PCA (TPCA) and probabilistic principal geodesic analysis (PPGA).

How temperament and personality contribute to the maladjustment of children with autism.

PubMed

De Pauw, Sarah S W; Mervielde, Ivan; Van Leeuwen, Karla G; De Clercq, Barbara J

2011-02-01

To test the spectrum hypothesis--postulating that clinical and non-clinical samples are primarily differentiated by mean-level differences--, this study evaluates differences in parent-rated temperament, personality and maladjustment among a low-symptom (N = 81), a high-symptom (N = 94) ASD-group, and a comparison group (N = 500). These classic spectrum hypothesis tests are extended by adding tests for similarity in variances, reliabilities and patterns of covariation between relevant variables. Children with ASD exhibit more extreme means, except for dominance. The low- and high-symptom ASD-groups are primarily differentiated by mean sociability and internal distress. Striking similarities in reliability and pattern of covariation of variables suggest that comparable processes link traits to maladaptation in low- and high-symptom children with ASD and in children with and without autism.

PRIM versus CART in subgroup discovery: when patience is harmful.

PubMed

Abu-Hanna, Ameen; Nannings, Barry; Dongelmans, Dave; Hasman, Arie

2010-10-01

We systematically compare the established algorithms CART (Classification and Regression Trees) and PRIM (Patient Rule Induction Method) in a subgroup discovery task on a large real-world high-dimensional clinical database. Contrary to current conjectures, PRIM's performance was generally inferior to CART's. PRIM often considered "peeling of" a large chunk of data at a value of a relevant discrete ordinal variable unattractive, ultimately missing an important subgroup. This finding has considerable significance in clinical medicine where ordinal scores are ubiquitous. PRIM's utility in clinical databases would increase when global information about (ordinal) variables is better put to use and when the search algorithm keeps track of alternative solutions.

Otofaciocervical syndrome and metachondromatosis in a girl: Presentation of a novel association and remarks on clinical variability of branchial-arch disorders.

PubMed

Salinas-Torres, Victor M; Salinas-Torres, Rafael A

2016-06-01

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial, ear, branchial, and musculoskeletal anomalies, along with hearing loss and mild intellectual disability. Clinically, its distinction from branchiootorenal syndrome can be difficult. To date, the coexistence of OFCS and metachondromatosis has not been reported. Here, we describe a sporadic patient with both OFCS and metachondromatosis. This novel association prompts us to do some remarks on the clinical variability of branchial-arch disorders; in fact, our observations are consistent with the highly variable expressivity of OFCS and illustrate the need of a more accurate characterization of these branchial-arch disorders. In the meantime, involvement of clavicles, scapulae and shoulders remains a distinctive feature of OFCS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the Environmental Bias on Accelerometer-Measured Total Daily Activity Counts and Owner Survey Responses in Dogs with Osteoarthritis.

PubMed

Katz, Erin M; Scott, Ruth M; Thomson, Christopher B; Mesa, Eileen; Evans, Richard; Conzemius, Michael G

2017-11-01

Objective  To determine if environmental variables affect the average daily activity counts (AC) of dogs with osteoarthritis (OA) and/or owners' perception of their dog's clinical signs or quality of life. Methods  The AC and Canine Brief Pain Inventory (CBPI) owner questionnaires of 62 dogs with OA were compared with daily environmental variables including the following: average temperature (°C), high temperature (°C), low temperature (°C), relative humidity (%), total precipitation (mm), average barometric pressure (hPa) and total daylight hours. Results  Daily AC significantly correlated with average temperature and total daylight hours, but average temperature and total daylight hours accounted for less than 1% of variation in AC. No other significant relationships were found between daily AC and daily high temperature, low temperature, relative humidity, total precipitation or average barometric pressure. No statistical relationship was found between daily AC and the CBPI, nor between environmental variables and the CBPI. Canine Brief Pain Inventory scores for pain severity and pain interference decreased significantly over the test period. Clinical Significance  The relationship between daily AC and average temperature and total daylight hours was significant, but unlikely to be clinically significant. Thus, environmental variables do not appear to have a clinically relevant bias on AC or owner CBPI questionnaires. The decrease over time in CBPI pain severity and pain interference values suggests owners completing the CBPI in this study were influenced by a caregiver placebo effect. Schattauer GmbH Stuttgart.

Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov.

PubMed

Cahan, Amos; Anand, Vibha

2017-01-01

ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants' baseline measures. The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). "Age" as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted.

Variability of carotid artery measurements on 3-Tesla MRI and its impact on sample size calculation for clinical research.

PubMed

Syed, Mushabbar A; Oshinski, John N; Kitchen, Charles; Ali, Arshad; Charnigo, Richard J; Quyyumi, Arshed A

2009-08-01

Carotid MRI measurements are increasingly being employed in research studies for atherosclerosis imaging. The majority of carotid imaging studies use 1.5 T MRI. Our objective was to investigate intra-observer and inter-observer variability in carotid measurements using high resolution 3 T MRI. We performed 3 T carotid MRI on 10 patients (age 56 +/- 8 years, 7 male) with atherosclerosis risk factors and ultrasound intima-media thickness > or =0.6 mm. A total of 20 transverse images of both right and left carotid arteries were acquired using T2 weighted black-blood sequence. The lumen and outer wall of the common carotid and internal carotid arteries were manually traced; vessel wall area, vessel wall volume, and average wall thickness measurements were then assessed for intra-observer and inter-observer variability. Pearson and intraclass correlations were used in these assessments, along with Bland-Altman plots. For inter-observer variability, Pearson correlations ranged from 0.936 to 0.996 and intraclass correlations from 0.927 to 0.991. For intra-observer variability, Pearson correlations ranged from 0.934 to 0.954 and intraclass correlations from 0.831 to 0.948. Calculations showed that inter-observer variability and other sources of error would inflate sample size requirements for a clinical trial by no more than 7.9%, indicating that 3 T MRI is nearly optimal in this respect. In patients with subclinical atherosclerosis, 3 T carotid MRI measurements are highly reproducible and have important implications for clinical trial design.

Harmonization of blood-based indicators of iron status: making the hard work matter.

PubMed

Hoofnagle, Andrew N

2017-12-01

Blood-based indicators that are used in the assessment of iron status are assumed to be accurate. In practice, inaccuracies in these measurements exist and stem from bias and variability. For example, the analytic variability of serum ferritin measurements across laboratories is very high (>15%), which increases the rate of misclassification in clinical and epidemiologic studies. The procedures that are used in laboratory medicine to minimize bias and variability could be used effectively in clinical research studies, particularly in the evaluation of iron deficiency and its associated anemia in pregnancy and early childhood and in characterizing states of iron repletion and excess. The harmonization and standardization of traditional and novel bioindicators of iron status will allow results from clinical studies to be more meaningfully translated into clinical practice by providing a firm foundation for clinical laboratories to set appropriate cutoffs. In addition, proficiency testing monitors the performance of the methods over time. It is important that measures of iron status be evaluated, validated, and performed in a manner that is consistent with standard procedures in laboratory medicine. © 2017 American Society for Nutrition.

Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.

PubMed

Lindholm, Daniel; Lindbäck, Johan; Armstrong, Paul W; Budaj, Andrzej; Cannon, Christopher P; Granger, Christopher B; Hagström, Emil; Held, Claes; Koenig, Wolfgang; Östlund, Ollie; Stewart, Ralph A H; Soffer, Joseph; White, Harvey D; de Winter, Robbert J; Steg, Philippe Gabriel; Siegbahn, Agneta; Kleber, Marcus E; Dressel, Alexander; Grammer, Tanja B; März, Winfried; Wallentin, Lars

2017-08-15

Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Monoclonal protein reference change value as determined by gel-based serum protein electrophoresis.

PubMed

Salamatmanesh, Mina; McCudden, Christopher R; McCurdy, Arleigh; Booth, Ronald A

2018-01-01

The International Myeloma Working Group recommendations for monitoring disease progression or response include quantitation of the involved monoclonal immunoglobulin. They have defined the minimum change criteria of ≧25% with an absolute change of no <5g/L for either minimal response or progression. Limited evidence is available to accurately determine the magnitude of change in a monoclonal protein to reflect a true change in clinical status. Here we determined the analytical and biological variability of monoclonal proteins in stable monoclonal gammopathy of undetermined significance (MGUS) patients. Analytical variability (CVa) of normal protein fractions and monoclonal proteins were assessed agarose gel-based serum protein electrophoresis. Sixteen clinically stable MGUS patients were identified from our clinical hematology database. Individual biological variability (CVi) was determined and used to calculate a monoclonal protein reference change value (RCV). Analytical variability of the normal protein fractions (albumin, alpha-1, alpha-2, beta, total gamma) ranged from 1.3% for albumin to 5.8% for the alpha-1 globulins. CVa of low (5.6g/L) and high (32.2g/L) concentration monoclonal proteins were 3.1% and 22.2%, respectively. Individual CVi of stable patients ranged from 3.5% to 24.5% with a CVi of 12.9%. The reference change value (RCV) at a 95% probability was determined to be 36.7% (low) 39.6% (high) using our CVa and CVi. Serial monitoring of monoclonal protein concentration is important for MGUS and multiple myeloma patients. Accurate criteria for interpreting a change in monoclonal protein concentration are required for appropriate decision making. We used QC results and real-world conditions to assess imprecision of serum protein fractions including low and high monoclonal protein fractions and clinically stable MGUS patients to determine CVi and RCV. The calculated RCVs of 36.7% (low) and 39.6% (high) in this study were greater that reported previously and greater than the established criteria for relapse. Response criteria may be reassessed to increase sensitivity and specificity for detection of response. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Proposed clinical pathway for nonoperative management of high-grade pediatric pancreatic injuries based on a multicenter analysis: A pediatric trauma society collaborative.

PubMed

Naik-Mathuria, Bindi J; Rosenfeld, Eric H; Gosain, Ankush; Burd, Randall; Falcone, Richard A; Thakkar, Rajan; Gaines, Barbara; Mooney, David; Escobar, Mauricio; Jafri, Mubeen; Stallion, Anthony; Klinkner, Denise B; Russell, Robert; Campbell, Brendan; Burke, Rita V; Upperman, Jeffrey; Juang, David; St Peter, Shawn; Fenton, Stephon J; Beaudin, Marianne; Wills, Hale; Vogel, Adam; Polites, Stephanie; Pattyn, Adam; Leeper, Christine; Veras, Laura V; Maizlin, Ilan; Thaker, Shefali; Smith, Alexis; Waddell, Megan; Drews, Joseph; Gilmore, James; Armstrong, Lindsey; Sandler, Alexis; Moody, Suzanne; Behrens, Brandon; Carmant, Laurence

2017-10-01

Guidelines for nonoperative management (NOM) of high-grade pancreatic injuries in children have not been established, and wide practice variability exists. The purpose of this study was to evaluate common clinical strategies across multiple pediatric trauma centers to develop a consensus-based standard clinical pathway. A multicenter, retrospective review was conducted of children with high-grade (American Association of Surgeons for Trauma grade III-V) pancreatic injuries treated with NOM between 2010 and 2015. Data were collected on demographics, clinical management, and outcomes. Eighty-six patients were treated at 20 pediatric trauma centers. Median age was 9 years (range, 1-18 years). The majority (73%) of injuries were American Association of Surgeons for Trauma grade III, 24% were grade IV, and 3% were grade V. Median time from injury to presentation was 12 hours and median ISS was 16 (range, 4-66). All patients had computed tomography scan and serum pancreatic enzyme levels at presentation, but serial enzyme level monitoring was variable. Pancreatic enzyme levels did not correlate with injury grade or pseudocyst development. Parenteral nutrition was used in 68% and jejunal feeds in 31%. 3Endoscopic retrograde cholangiopancreatogram was obtained in 25%. An organized peripancreatic fluid collection present for at least 7 days after injury was identified in 59% (42 of 71). Initial management of these included: observation 64%, percutaneous drain 24%, and endoscopic drainage 10% and needle aspiration 2%. Clear liquids were started at a median of 6 days (IQR, 3-13 days) and regular diet at a median of 8 days (IQR 4-20 days). Median hospitalization length was 13 days (IQR, 7-24 days). Injury grade did not account for prolonged time to initiating oral diet or hospital length; indicating that the variability in these outcomes was largely due to different surgeon preferences. High-grade pancreatic injuries in children are rare and significant variability exists in NOM strategies, which may affect outcomes and effective resource utilization. A standard clinical pathway is proposed. Therapeutic/care management, level V (case series).

The impact of glycaemic variability on wound healing in the diabetic foot - A retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic.

PubMed

Dhatariya, Ketan K; Li Ping Wah-Pun Sin, Edwin; Cheng, Joyce Oi Suet; Li, Francesca Yan Nok; Yue, Anson Wei Yue; Gooday, Catherine; Nunney, Ian

2018-01-01

Glycaemic variability - the visit-to-visit variation in HbA1c - plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. A retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. 629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8-102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2-101.2) vs 126.9 days (102.0-158.0) in the high Hb1Ac variability group (p = .032). Those with low HbA1c (<58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5-90.8] vs 111.0 days [92.0-134.0], p = .007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p = .007). Our data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

[Predictive ability of clinical parameters of bacteremia in hemodialysed patients].

PubMed

Egea, Ana L; Vilaró, Mario; De la Fuente, Jorge; Cuestas, Eduardo; Bongiovanni, María E

2012-01-01

No clinical events to differentiate bacteteremia from other pathologies in hemodialysis patients therefore the physicians makes diagnosis and treatment decisions based on clinical evidence an local epidemiology. the aim of this work was to study the frequency of microorganism isolated from blood culture of hemodialysis patients with suspected bacteraemia and evaluate Sensitivity (S) and Specificity (E) of medical diagnostic orientation in this cases of suspected Materials and methods: we performed an observational and prospective study for one year in hemodialysis patient with suspected bacteremia. We evaluated blood pressure, temperature (Tº), altered conscious state (AEC), respiratory frequency (FR), chills (ESC),diarrhea (DIARR), blood culture results and microbiological identification. We work with the mean ± standar desviation for continuous variables and frequencies for categorical variables We analyzed S, E, negative predictive value (VPN), positive predictive value (VPP) RESULTADOS: a total of 87 events with suspected bacteremia 34 (39%) were confirmed with positive blood culture the most common microorganisms were cocci Gram positive (CGP) 65%, Most relevant clinical variables were PCP ≥ 2 (VPN 81%), Tº ≥ 38 (VPN 76%) and AEC (E 98% y VPP 80%). CGP were the most prevalent microorganisms None of the clinical variables shows high S and E indicating low usefulness as a predictive tool of bacteremia Excepting AEC with E98% and VPP 80% but it would be necessary to evaluate this variable with a more number patient. Results justify to routine HC use like diagnostic tool.

Molar Functional Relations and Clinical Behavior Analysis: Implications for Assessment and Treatment

ERIC Educational Resources Information Center

Waltz, Thomas J.; Follette, William C.

2009-01-01

The experimental analysis of behavior has identified several molar functional relations that are highly relevant to clinical behavior analysis. These include matching, discounting, momentum, and variability. Matching provides a broader analysis of how multiple sources of reinforcement influence how individuals choose to allocate their time and…

Prediction of Osteopathic Medical School Performance on the basis of MCAT score, GPA, sex, undergraduate major, and undergraduate institution.

PubMed

Dixon, Donna

2012-04-01

The relationships of students' preadmission academic variables, sex, undergraduate major, and undergraduate institution to academic performance in medical school have not been thoroughly examined. To determine the ability of students' preadmission academic variables to predict osteopathic medical school performance and whether students' sex, undergraduate major, or undergraduate institution influence osteopathic medical school performance. The study followed students who graduated from New York College of Osteopathic Medicine of New York Institute of Technology in Old Westbury between 2003 and 2006. Student preadmission data were Medical College Admission Test (MCAT) scores, undergraduate grade point averages (GPAs), sex, undergraduate major, and undergraduate institutional selectivity. Medical school performance variables were GPAs, clinical performance (ie, clinical subject examinations and clerkship evaluations), and scores on the Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) Level 1 and Level 2-Clinical Evaluation (CE). Data were analyzed with Pearson product moment correlation coefficients and multivariate linear regression analyses. Differences between student groups were compared with the independent-samples, 2-tailed t test. A total of 737 students were included. All preadmission academic variables, except nonscience undergraduate GPA, were statistically significant predictors of performance on COMLEX-USA Level 1, and all preadmission academic variables were statistically significant predictors of performance on COMLEX-USA Level 2-CE. The MCAT score for biological sciences had the highest correlation among all variables with COMLEX-USA Level 1 performance (Pearson r=0.304; P<.001) and Level 2-CE performance (Pearson r=0.272; P<.001). All preadmission variables were moderately correlated with the mean clinical subject examination scores. The mean clerkship evaluation score was moderately correlated with mean clinical examination results (Pearson r=0.267; P<.001) and COMLEX-USA Level 2-CE performance (Pearson r=0.301; P<.001). Clinical subject examination scores were highly correlated with COMLEX-USA Level 2-CE scores (Pearson r=0.817; P<.001). No statistically significant difference in medical school performance was found between students with science and nonscience undergraduate majors, nor was undergraduate institutional selectivity a factor influencing performance. Students' preadmission academic variables were predictive of osteopathic medical school performance, including GPAs, clinical performance, and COMLEX-USA Level 1 and Level 2-CE results. Clinical performance was predictive of COMLEX-USA Level 2-CE performance.

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

PubMed

Gong, Xiajing; Hu, Meng; Zhao, Liang

2018-05-01

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Factors related to clinical pregnancy after vitrified-warmed embryo transfer: a retrospective and multivariate logistic regression analysis of 2313 transfer cycles.

PubMed

Shi, Wenhao; Zhang, Silin; Zhao, Wanqiu; Xia, Xue; Wang, Min; Wang, Hui; Bai, Haiyan; Shi, Juanzi

2013-07-01

What factors does multivariate logistic regression show to be significantly associated with the likelihood of clinical pregnancy in vitrified-warmed embryo transfer (VET) cycles? Assisted hatching (AH) and if the reason to freeze embryos was to avoid the risk of ovarian hyperstimulation syndrome (OHSS) were significantly positively associated with a greater likelihood of clinical pregnancy. Single factor analysis has shown AH, number of embryos transferred and the reason of freezing for OHSS to be positively and damaged blastomere to be negatively significantly associated with the chance of clinical pregnancy after VET. It remains unclear what factors would be significant after multivariate analysis. The study was a retrospective analysis of 2313 VET cycles from 1481 patients performed between January 2008 and April 2012. A multivariate logistic regression analysis was performed to identify the factors to affect clinical pregnancy outcome of VET. There were 22 candidate variables selected based on clinical experiences and the literature. With the thresholds of α entry = α removal= 0.05 for both variable entry and variable removal, eight variables were chosen to contribute the multivariable model by the bootstrap stepwise variable selection algorithm (n = 1000). Eight variables were age at controlled ovarian hyperstimulation (COH), reason for freezing, AH, endometrial thickness, damaged blastomere, number of embryos transferred, number of good-quality embryos, and blood presence on transfer catheter. A descriptive comparison of the relative importance was accomplished by the proportion of explained variation (PEV). Among the reasons for freezing, the OHSS group showed a higher OR than the surplus embryo group when compared with other reasons for VET groups (OHSS versus Other, OR: 2.145; CI: 1.4-3.286; Surplus embryos versus Other, OR: 1.152; CI: 0.761-1.743) and high PEV (marginal 2.77%, P = 0.2911; partial 1.68%; CI of area under receptor operator characteristic curve (ROC): 0.5576-0.6000). AH also showed a high OR (OR: 2.105, CI: 1.554-2.85) and high PEV (marginal 1.97%; partial 1.02%; CI of area under ROC: 0.5344-0.5647). The number of good-quality embryos showed the highest marginal PEV and partial PEV (marginal 3.91%, partial 2.28%; CI of area under ROC: 0.5886-0.6343). This was a retrospective multivariate analysis of the data obtained in 5 years from a single IVF center. Repeated cycles in the same woman were treated as independent observations, which could introduce bias. Results are based on clinical pregnancy and not live births. Prospective analysis of a larger data set from a multicenter study based on live births is necessary to confirm the findings. Paying attention to the quality of embryos, the number of good embryos, AH and the reasons for freezing that are associated with clinical pregnancy after VET will assist the improvement of success rates.

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

PubMed

Barazzoni, R; Deutz, N E P; Biolo, G; Bischoff, S; Boirie, Y; Cederholm, T; Cuerda, C; Delzenne, N; Leon Sanz, M; Ljungqvist, O; Muscaritoli, M; Pichard, C; Preiser, J C; Sbraccia, P; Singer, P; Tappy, L; Thorens, B; Van Gossum, A; Vettor, R; Calder, P C

2017-04-01

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The many ways sputum flows - Dealing with high within-subject variability in cystic fibrosis sputum rheology.

PubMed

Radtke, Thomas; Böni, Lukas; Bohnacker, Peter; Fischer, Peter; Benden, Christian; Dressel, Holger

2018-04-21

We evaluated test-retest reliability of sputum viscoelastic properties in clinically stable patients with cystic fibrosis (CF). Data from a prospective, randomized crossover study was used to determine within-subject variability of sputum viscoelasticity (G', storage modulus and G", loss modulus at 1 and 10 rad s -1 ) and solids content over three consecutive visits. Precision of sputum properties was quantified by within-subject standard deviation (SD ws ), coefficient of variation (CV) and intraclass correlation coefficients (ICC). Fifteen clinically stable adults with CF (FEV 1 range 24-94% predicted) were included. No differences between study visits (mean ± SD 8 ± 2 days) were observed for any sputum rheology measure. CV's for G', G" and solids content ranged between 40.3-45.3% and ICC's between 0.21-0.42 indicating poor to fair test-retest reliability. Short-term within-subject variability of sputum properties is high in clinically stable adults with CF. Investigators applying shear rheology experiments in future prospective studies should consider using multiple measurements aiming to increase precision of sputum rheological outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.

PubMed

Graul-Neumann, Luitgard M; Hausser, Ingrid; Essayie, Maximilian; Rauch, Anita; Kraus, Cornelia

2008-04-15

Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. Only seven ADCL families with mutations in the elastin gene (ELN) have been described previously. We present morphological and molecular genetic studies in a cutis laxa kindred with a previously undescribed highly variable phenotype caused by a novel ELN mutation c.1621 C > T. The proband presented with severe cutis laxa, severe congenital lung disease previously undescribed in ADCL and pulmonary artery disease, which is often seen in ARCL but rare in ADCL. He also developed infantile spasms (OMIM 308350; West syndrome), which we consider a coincidental association although recessive cutis laxa or even digenic inheritance cannot be excluded. Electron microscopy of the proband's dermis revealed only mild rarefication of elastic fibers (in contrast to most recessive cutis laxa types). Apart from mild elastic fiber fragmentation, dermal morphology of the proband's father was within normal range. Molecular analysis of the ELN gene using genomic DNA from blood and RNA from cultured skin fibroblasts indicated a novel splice site mutation in the proband and his clinically healthy father. Analysis of ELN expression in fibroblasts provided evidence for a dominant-negative effect in the child, while due to an unknown mechanism, the father showed haploinsufficiency which might explain the significant clinical variability. Copyright 2008 Wiley-Liss, Inc.

Frequent hospital admissions in Singapore: clinical risk factors and impact of socioeconomic status.

PubMed

Low, Lian Leng; Tay, Wei Yi; Ng, Matthew Joo Ming; Tan, Shu Yun; Liu, Nan; Lee, Kheng Hock

2018-01-01

Frequent admitters to hospitals are high-cost patients who strain finite healthcare resources. However, the exact risk factors for frequent admissions, which can be used to guide risk stratification and design effective interventions locally, remain unknown. Our study aimed to identify the clinical and sociodemographic risk factors associated with frequent hospital admissions in Singapore. An observational study was conducted using retrospective 2014 data from the administrative database at Singapore General Hospital, Singapore. Variables were identified a priori and included patient demographics, comorbidities, prior healthcare utilisation, and clinical and laboratory variables during the index admission. Multivariate logistic regression analysis was used to identify independent risk factors for frequent admissions. A total of 16,306 unique patients were analysed and 1,640 (10.1%) patients were classified as frequent admitters. On multivariate logistic regression, 16 variables were independently associated with frequent hospital admissions, including age, cerebrovascular disease, history of malignancy, haemoglobin, serum creatinine, serum albumin, and number of specialist outpatient clinic visits, emergency department visits, admissions preceding index admission and medications dispensed at discharge. Patients staying in public rental housing had a 30% higher risk of being a frequent admitter after adjusting for demographics and clinical conditions. Our study, the first in our knowledge to examine the clinical risk factors for frequent admissions in Singapore, validated the use of public rental housing as a sensitive indicator of area-level socioeconomic status in Singapore. These risk factors can be used to identify high-risk patients in the hospital so that they can receive interventions that reduce readmission risk. Copyright: © Singapore Medical Association

External Validation of the HERNIAscore: An Observational Study.

PubMed

Cherla, Deepa V; Moses, Maya L; Mueck, Krislynn M; Hannon, Craig; Ko, Tien C; Kao, Lillian S; Liang, Mike K

2017-09-01

The HERNIAscore is a ventral incisional hernia (VIH) risk assessment tool that uses only preoperative variables and predictable intraoperative variables. The aim of this study was to validate and modify, if needed, the HERNIAscore in an external dataset. This was a retrospective observational study of all patients undergoing resection for gastrointestinal malignancy from 2011 through 2015 at a safety-net hospital. The primary end point was clinical postoperative VIH. Patients were stratified into low-risk, medium-risk, and high-risk groups based on HERNIAscore. A revised HERNIAscore was calculated with the addition of earlier abdominal operation as a categorical variable. Cox regression of incisional hernia with stratification by risk class was performed. Incidence rates of clinical VIH formation within each risk class were also calculated. Two hundred and forty-seven patents were enrolled. On Cox regression, in addition to the 3 variables of the HERNIAscore (BMI, COPD, and incision length), earlier abdominal operation was also predictive of VIH. The revised HERNIAscore demonstrated improved predictive accuracy for clinical VIH. Although the original HERNIAscore effectively stratified the risk of an incisional radiographic VIH developing, the revised HERNIAscore provided a statistically significant stratification for both clinical and radiographic VIHs in this patient cohort. We have externally validated and improved the HERNIAscore. The revised HERNIAscore uses BMI, incision length, COPD, and earlier abdominal operation to predict risk of postoperative incisional hernia. Future research should assess methods to prevent incisional hernias in moderate-to-high risk patients. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of trotting speed on kinematic variables measured by use of extremity-mounted inertial measurement units in nonlame horses performing controlled treadmill exercise.

PubMed

Cruz, Antonio M; Vidondo, Beatriz; Ramseyer, Alessandra A; Maninchedda, Ugo E

2018-02-01

OBJECTIVE To assess effects of speed on kinematic variables measured by use of extremity-mounted inertial measurement units (IMUs) in nonlame horses performing controlled exercise on a treadmill. ANIMALS 10 nonlame horses. PROCEDURES 6 IMUs were attached at predetermined locations on 10 nonlame Franches Montagnes horses. Data were collected in triplicate during trotting at 3.33 and 3.88 m/s on a high-speed treadmill. Thirty-three selected kinematic variables were analyzed. Repeated-measures ANOVA was used to assess the effect of speed. RESULTS Significant differences between the 2 speeds were detected for most temporal (11/14) and spatial (12/19) variables. The observed spatial and temporal changes would translate into a gait for the higher speed characterized by increased stride length, protraction and retraction, flexion and extension, mediolateral movement of the tibia, and symmetry, but with similar temporal variables and a reduction in stride duration. However, even though the tibia coronal range of motion was significantly different between speeds, the high degree of variability raised concerns about whether these changes were clinically relevant. For some variables, the lower trotting speed apparently was associated with more variability than was the higher trotting speed. CONCLUSIONS AND CLINICAL RELEVANCE At a higher trotting speed, horses moved in the same manner (eg, the temporal events investigated occurred at the same relative time within the stride). However, from a spatial perspective, horses moved with greater action of the segments evaluated. The detected changes in kinematic variables indicated that trotting speed should be controlled or kept constant during gait evaluation.

Multilevel Predictors of Clinic Adoption of State-Supported Trainings in Children’s Services

PubMed Central

Olin, Su-chin Serene; Chor, Ka Ho Brian; Weaver, James; Duan, Naihua; Kerker, Bonnie D.; Clark, Lisa J.; Cleek, Andrew F.; Hoagwood, Kimberly Eaton; Horwitz, Sarah McCue

2015-01-01

Objective Characteristics associated with participation in training in evidence-informed business and clinical practices by 346 outpatient mental health clinics licensed to treat youths in New York State were examined. Methods Clinic characteristics extracted from state administrative data were used as proxies for variables that have been linked with adoption of innovation (extraorganizational factors, agency factors, clinic provider-level profiles, and clinic client-level profiles). Multiple logistic regression models were used to assess the independent effects of theoretical variables on the clinics’ participation in state-supported business and clinical trainings between September 2011 and August 2013 and on the intensity of participation (low or high). Interaction effects between clinic characteristics and outcomes were explored. Results Clinic characteristics were predictive of any participation in trainings but were less useful in predicting intensity of participation. Clinics affiliated with larger (adjusted odds ratio [AOR]=.65, p<.01), more efficient agencies (AOR=.62, p<.05) and clinics that outsourced more clinical services (AOR=.60, p<.001) had lower odds of participating in any business-practice trainings. Participation in business trainings was associated with interaction effects between agency affiliation (hospital or community) and clinical staff capacity. Clinics with more full-time-equivalent clinical staff (AOR=1.52, p<.01) and a higher proportion of clients under age 18 (AOR=1.90, p<.001) had higher odds of participating in any clinical trainings. Participating clinics with larger proportions of youth clients had greater odds of being high adopters of clinical trainings (odds ratio=1.54, p<.01). Conclusions Clinic characteristics associated with uptake of business and clinical training could be used to target state technical assistance efforts. PMID:25686815

Episiotomy increases perineal laceration length in primiparous women.

PubMed

Nager, C W; Helliwell, J P

2001-08-01

The aim of this study was to determine the clinical factors that contribute to posterior perineal laceration length. A prospective observational study was performed in 80 consenting, mostly primiparous women with term pregnancies. Posterior perineal lacerations were measured immediately after delivery. Numerous maternal, fetal, and operator variables were evaluated against laceration length and degree of tear. Univariate and multivariate regression analyses were performed to evaluate laceration length and parametric clinical variables. Nonparametric clinical variables were evaluated against laceration length by the Mann-Whitney U test. A multivariate stepwise linear regression equation revealed that episiotomy adds nearly 3 cm to perineal lacerations. Tear length was highly associated with the degree of tear (R = 0.86, R(2) = 0.73) and the risk of recognized anal sphincter disruption. None of 35 patients without an episiotomy had a recognized anal sphincter disruption, but 6 of 27 patients with an episiotomy did (P <.001). Body mass index was the only maternal or fetal variable that showed even a slight correlation with laceration length (R = 0.30, P =.04). Episiotomy is the overriding determinant of perineal laceration length and recognized anal sphincter disruption.

Forms of work organization and associations with shoulder disorders: Results from a French working population.

PubMed

Bodin, Julie; Garlantézec, Ronan; Costet, Nathalie; Descatha, Alexis; Fouquet, Natacha; Caroly, Sandrine; Roquelaure, Yves

2017-03-01

The aim of this study was to identify forms of work organization in a French region and to study associations with the occurrence of symptomatic and clinically diagnosed shoulder disorders in workers. Workers were randomly included in this cross-sectional study from 2002 to 2005. Sixteen organizational variables were assessed by a self-administered questionnaire: i.e. shift work, job rotation, repetitiveness of tasks, paced work/automatic rate, work pace dependent on quantified targets, permanent controls or surveillance, colleagues' work and customer demand, and eight variables measuring decision latitude. Five forms of work organization were identified using hierarchical cluster analysis (HCA) of variables and HCA of workers: low decision latitude with pace constraints, medium decision latitude with pace constraints, low decision latitude with low pace constraints, high decision latitude with pace constraints and high decision latitude with low pace constraints. There were significant associations between forms of work organization and symptomatic and clinically-diagnosed shoulder disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding data requirements of retrospective studies.

PubMed

Shenvi, Edna C; Meeker, Daniella; Boxwala, Aziz A

2015-01-01

Usage of data from electronic health records (EHRs) in clinical research is increasing, but there is little empirical knowledge of the data needed to support multiple types of research these sources support. This study seeks to characterize the types and patterns of data usage from EHRs for clinical research. We analyzed the data requirements of over 100 retrospective studies by mapping the selection criteria and study variables to data elements of two standard data dictionaries, one from the healthcare domain and the other from the clinical research domain. We also contacted study authors to validate our results. The majority of variables mapped to one or to both of the two dictionaries. Studies used an average of 4.46 (range 1-12) data element types in the selection criteria and 6.44 (range 1-15) in the study variables. The most frequently used items (e.g., procedure, condition, medication) are often available in coded form in EHRs. Study criteria were frequently complex, with 49 of 104 studies involving relationships between data elements and 22 of the studies using aggregate operations for data variables. Author responses supported these findings. The high proportion of mapped data elements demonstrates the significant potential for clinical data warehousing to facilitate clinical research. Unmapped data elements illustrate the difficulty in developing a complete data dictionary. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

PubMed Central

Khoury, Nabil T.; Hossain, Md Monir; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2012-01-01

Objective To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and Methods We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. Conclusion Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation. PMID:23218086

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

PubMed Central

Blanco-Calvo, Moisés; Concha, Ángel; Figueroa, Angélica; Garrido, Federico; Valladares-Ayerbes, Manuel

2015-01-01

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. PMID:26084042

Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.

PubMed

Dell'Isola, A; Allan, R; Smith, S L; Marreiros, S S P; Steultjens, M

2016-10-12

Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

PubMed

Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

2008-07-01

To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

Clinical and genetic characterization of a founder PKHD1 mutation in Afrikaners with ARPKD.

PubMed

Lambie, Lindsay; Amin, Rasheda; Essop, Fahmida; Cnaan, Avital; Krause, Amanda; Guay-Woodford, Lisa M

2015-02-01

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) occurs in 1:20,000 live births. Disease expression is widely variable, with approximately 30 % of affected neonates dying perinatally, while others survive to adulthood. Mutations at the PKHD1 locus are responsible for all typical presentations. The objectives of this study were to define the clinical and genetic characteristics in a cohort of South African patients of Afrikaner origin, a population with a high prevalence of ARPKD. DNA from the cohort was analyzed for background haplotypes and the p.M627K mutation previously identified in two unrelated Afrikaner patients. The clinical phenotype of the homozygous group was characterized. Analysis of 36 Afrikaner families revealed that 27 patients, from 24 (67 %) families, were homozygous for the p.M627K substitution, occurring on a common haplotype. The clinical phenotype of the homozygous individuals was variable. Our data provide strong evidence that the p.M627K substitution is a founder mutation in the Afrikaner population and can be used for streamlined diagnostic testing for at-risk pregnancies. The observed clinical variability suggests that disease expression is modulated by other genetic loci or by gene-environment interactions.

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study.

PubMed

Porcino, Antony J; Boon, Heather S; Page, Stacey A; Verhoef, Marja J

2011-09-20

Therapeutic massage and bodywork (TMB) practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Of the 5242 distributed surveys, 791 were returned (15.1%). Practitioners were predominantly female (91.7%), worked in a range of environments, primarily private (44.4%) and home clinics (35.4%), and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%), with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient's treatment through a highly adaptive process. Therefore, treatment provision is likely unique to each practitioner. These results may be of interest to researchers considering similar practice issues in other professions. The use of a combined-methods design effectively captured this complexity of TMB practice. TMB research needs to consider research approaches that can capture or adapt to the individualized nature of practice.

Molecular method for the characterization of Coxiella burnetii from clinical and environmental samples: variability of genotypes in Spain

PubMed Central

2012-01-01

Background Coxiella burnetii is a highly clonal microorganism which is difficult to culture, requiring BSL3 conditions for its propagation. This leads to a scarce availability of isolates worldwide. On the other hand, published methods of characterization have delineated up to 8 different genomic groups and 36 genotypes. However, all these methodologies, with the exception of one that exhibited limited discriminatory power (3 genotypes), rely on performing between 10 and 20 PCR amplifications or sequencing long fragments of DNA, which make their direct application to clinical samples impracticable and leads to a scarce accessibility of data on the circulation of C. burnetii genotypes. Results To assess the variability of this organism in Spain, we have developed a novel method that consists of a multiplex (8 targets) PCR and hybridization with specific probes that reproduce the previous classification of this organism into 8 genomic groups, and up to 16 genotypes. It allows for a direct characterization from clinical and environmental samples in a single run, which will help in the study of the different genotypes circulating in wild and domestic cycles as well as from sporadic human cases and outbreaks. The method has been validated with reference isolates. A high variability of C. burnetii has been found in Spain among 90 samples tested, detecting 10 different genotypes, being those adaA negative associated with acute Q fever cases presenting as fever of intermediate duration with liver involvement and with chronic cases. Genotypes infecting humans are also found in sheep, goats, rats, wild boar and ticks, and the only genotype found in cattle has never been found among our clinical samples. Conclusions This newly developed methodology has permitted to demonstrate that C. burnetii is highly variable in Spain. With the data presented here, cattle seem not to participate in the transmission of C. burnetii to humans in the samples studied, while sheep, goats, wild boar, rats and ticks share genotypes with the human population. PMID:22656068

Pharmacokinetic variability, efficacy and tolerability of eslicarbazepine acetate-A national approach to the evaluation of therapeutic drug monitoring data and clinical outcome.

PubMed

Svendsen, Torleiv; Brodtkorb, Eylert; Reimers, Arne; Molden, Espen; Sætre, Erik; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-01-01

Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory epilepsy. This retrospective observational study included TDM-data from the main laboratories and population data from the Norwegian Prescription Database in Norway, in addition to clinical data from medical records of adult patients using ESL for up to three years, whenever possible. TDM-data from 168 patients were utilized for assessment of pharmacokinetic variability, consisting of 71% of the total number of patients in Norway using ESL, 2011-14. Median daily dose of ESL was 800mg (range 400-1600mg), and median serum concentration of ESL was 53μmol/L (range 13-132μmol/L). Inter-patient variability of ESL was extensive, with 25-fold variability in concentration/dose ratios. Additional clinical data were available from 104 adult patients out of the 168, all with drug resistant focal epilepsy. After 1, 2 and 3 years follow-up, the retention rate of ESL was 83%, 72% and 64%, respectively. ESL was generally well tolerated as add-on treatment, but sedation, cognitive impairment and hyponatremia were reported. Hyponatremia (sodium <137mmol/L) was present in 36% of the patients, and lead to discontinuation in three. Pharmacokinetic variability of ESL was extensive and the demonstration of usefulness of TDM requires further studies. In patients with drug resistant focal Epilepsy, the high retention rate indicated good efficacy and tolerability. Hyponatremia was observed in one third of the patients. The present results point to a need for individualization of treatment and TDM may be useful. Copyright © 2016 Elsevier B.V. All rights reserved.

Heart rate variability alterations in late life depression: A meta-analysis.

PubMed

Brown, Lydia; Karmakar, Chandan; Gray, Richard; Jindal, Ripu; Lim, Terrence; Bryant, Christina

2018-08-01

There is strong evidence for a bi-directional relationship between heart-health and depression in later life, but the physiological mechanisms underlying this relationship remain unclear. Heart rate variability is one promising factor that might help explain this relationship. We present results of a meta-analysis that considers heart rate variability alterations in older adults with depression. Literature search of Embase, PsychInfo and Medline revealed five clinical studies and six observational studies that examined the relationship between heart rate variability and depression in adults with a mean age over 60. These studies were included in this meta-analysis. Heart rate variability was reduced among older adults with clinical depression (N = 550), relative to healthy controls (Hedges' g = -0.334, 95%CI [-0.579, -0.090], p = .007). When high-frequency and low-frequency heart rate variability were investigated separately, only low-frequency heart rate variability was significantly reduced in depressed patients (Hedges' g = -0.626, 95%CI [-1.083, -0.169], p = .007). A similar but weaker pattern of results was found in the observational studies. Most findings remained significant among unmedicated depressed older adults. Evidence of effect-size heterogeneity was found in the clinical studies, indicating the need for more well-designed research in the area. Heart rate variability is reduced among older adults with depression, and this effect is not fully attributable to antidepressant medication use. Specifically, low-frequency heart rate variability may be reduced in depressed older adults. Heart rate variability warrants further attention, as it could help inform research into the prevention and treatment of depression in later life. Copyright © 2018 Elsevier B.V. All rights reserved.

[Application of variable magnetic fields in medicine--15 years experience].

PubMed

Sieroń, Aleksander; Cieślar, Grzegorz

2003-01-01

The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson's disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.

The Computer Book of the Internal Medicine Resident: competence acquisition and achievement of learning objectives.

PubMed

Oristrell, J; Oliva, J C; Casanovas, A; Comet, R; Jordana, R; Navarro, M

2014-01-01

The Computer Book of the Internal Medicine resident (CBIMR) is a computer program that was validated to analyze the acquisition of competences in teams of Internal Medicine residents. To analyze the characteristics of the rotations during the Internal Medicine residency and to identify the variables associated with the acquisition of clinical and communication skills, the achievement of learning objectives and resident satisfaction. All residents of our service (n=20) participated in the study during a period of 40 months. The CBIMR consisted of 22 self-assessment questionnaires specific for each rotation, with items on services (clinical workload, disease protocolization, resident responsibilities, learning environment, service organization and teamwork) and items on educational outcomes (acquisition of clinical and communication skills, achievement of learning objectives, overall satisfaction). Associations between services features and learning outcomes were analyzed using bivariate and multivariate analysis. An intense clinical workload, high resident responsibilities and disease protocolization were associated with the acquisition of clinical skills. High clinical competence and teamwork were both associated with better communication skills. Finally, an adequate learning environment was associated with increased clinical competence, the achievement of educational goals and resident satisfaction. Potentially modifiable variables related with the operation of clinical services had a significant impact on the acquisition of clinical and communication skills, the achievement of educational goals, and resident satisfaction during the specialized training in Internal Medicine. Copyright © 2013 Elsevier España, S.L. All rights reserved.

IDENTIFYING GENETIC ASSOCIATIONS WITH VARIABILITY IN METABOLIC HEALTH AND BLOOD COUNT LABORATORY VALUES: DIVING INTO THE QUANTITATIVE TRAITS BY LEVERAGING LONGITUDINAL DATA FROM AN EHR.

PubMed

Verma, Shefali S; Lucas, Anastasia M; Lavage, Daniel R; Leader, Joseph B; Metpally, Raghu; Krishnamurthy, Sarathbabu; Dewey, Frederick; Borecki, Ingrid; Lopez, Alexander; Overton, John; Penn, John; Reid, Jeffrey; Pendergrass, Sarah A; Breitwieser, Gerda; Ritchie, Marylyn D

2017-01-01

A wide range of patient health data is recorded in Electronic Health Records (EHR). This data includes diagnosis, surgical procedures, clinical laboratory measurements, and medication information. Together this information reflects the patient's medical history. Many studies have efficiently used this data from the EHR to find associations that are clinically relevant, either by utilizing International Classification of Diseases, version 9 (ICD-9) codes or laboratory measurements, or by designing phenotype algorithms to extract case and control status with accuracy from the EHR. Here we developed a strategy to utilize longitudinal quantitative trait data from the EHR at Geisinger Health System focusing on outpatient metabolic and complete blood panel data as a starting point. Comprehensive Metabolic Panel (CMP) as well as Complete Blood Counts (CBC) are parts of routine care and provide a comprehensive picture from high level screening of patients' overall health and disease. We randomly split our data into two datasets to allow for discovery and replication. We first conducted a genome-wide association study (GWAS) with median values of 25 different clinical laboratory measurements to identify variants from Human Omni Express Exome beadchip data that are associated with these measurements. We identified 687 variants that associated and replicated with the tested clinical measurements at p<5×10-08. Since longitudinal data from the EHR provides a record of a patient's medical history, we utilized this information to further investigate the ICD-9 codes that might be associated with differences in variability of the measurements in the longitudinal dataset. We identified low and high variance patients by looking at changes within their individual longitudinal EHR laboratory results for each of the 25 clinical lab values (thus creating 50 groups - a high variance and a low variance for each lab variable). We then performed a PheWAS analysis with ICD-9 diagnosis codes, separately in the high variance group and the low variance group for each lab variable. We found 717 PheWAS associations that replicated at a p-value less than 0.001. Next, we evaluated the results of this study by comparing the association results between the high and low variance groups. For example, we found 39 SNPs (in multiple genes) associated with ICD-9 250.01 (Type-I diabetes) in patients with high variance of plasma glucose levels, but not in patients with low variance in plasma glucose levels. Another example is the association of 4 SNPs in UMOD with chronic kidney disease in patients with high variance for aspartate aminotransferase (discovery p-value: 8.71×10-09 and replication p-value: 2.03×10-06). In general, we see a pattern of many more statistically significant associations from patients with high variance in the quantitative lab variables, in comparison with the low variance group across all of the 25 laboratory measurements. This study is one of the first of its kind to utilize quantitative trait variance from longitudinal laboratory data to find associations among genetic variants and clinical phenotypes obtained from an EHR, integrating laboratory values and diagnosis codes to understand the genetic complexities of common diseases.

Classification of Suicide Attempts through a Machine Learning Algorithm Based on Multiple Systemic Psychiatric Scales.

PubMed

Oh, Jihoon; Yun, Kyongsik; Hwang, Ji-Hyun; Chae, Jeong-Ho

2017-01-01

Classification and prediction of suicide attempts in high-risk groups is important for preventing suicide. The purpose of this study was to investigate whether the information from multiple clinical scales has classification power for identifying actual suicide attempts. Patients with depression and anxiety disorders ( N  = 573) were included, and each participant completed 31 self-report psychiatric scales and questionnaires about their history of suicide attempts. We then trained an artificial neural network classifier with 41 variables (31 psychiatric scales and 10 sociodemographic elements) and ranked the contribution of each variable for the classification of suicide attempts. To evaluate the clinical applicability of our model, we measured classification performance with top-ranked predictors. Our model had an overall accuracy of 93.7% in 1-month, 90.8% in 1-year, and 87.4% in lifetime suicide attempts detection. The area under the receiver operating characteristic curve (AUROC) was the highest for 1-month suicide attempts detection (0.93), followed by lifetime (0.89), and 1-year detection (0.87). Among all variables, the Emotion Regulation Questionnaire had the highest contribution, and the positive and negative characteristics of the scales similarly contributed to classification performance. Performance on suicide attempts classification was largely maintained when we only used the top five ranked variables for training (AUROC; 1-month, 0.75, 1-year, 0.85, lifetime suicide attempts detection, 0.87). Our findings indicate that information from self-report clinical scales can be useful for the classification of suicide attempts. Based on the reliable performance of the top five predictors alone, this machine learning approach could help clinicians identify high-risk patients in clinical settings.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

PubMed

Smid, Jerusa; Studart, Adalberto; Landemberger, Michele Christine; Machado, Cleiton Fagundes; Nóbrega, Paulo Ribeiro; Canedo, Nathalie Henriques Silva; Schultz, Rodrigo Rizek; Naslavsky, Michel Satya; Rosemberg, Sérgio; Kok, Fernando; Chimelli, Leila; Martins, Vilma Regina; Nitrini, Ricardo

2017-06-01

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

Dropout revisited: patient- and therapist-initiated discontinuation of psychotherapy as a function of organizational instability.

PubMed

Werbart, Andrzej; Andersson, Håkan; Sandell, Rolf

2014-01-01

To explore the association between the stability or instability of services' organizational structure and patient- and therapist-initiated discontinuation of therapy in routine mental health. Three groups, comprising altogether 750 cases in routine mental health care in eight different clinics, were included: cases with patient-initiated discontinuation, therapist-initiated discontinuation, and patients remaining in treatment. Multilevel multinomial regression was used to estimate three models: An initial, unconditional intercept-only model, another one including patient variables, and a final model with significant patient and therapist variables including the organizational stability of the therapists' clinic. High between-therapist variability was noted. Odds ratios and significance tests indicated a strong association of organizational instability with patient-initiated premature termination in particular. The question of how organizational factors influence the treatment results needs further research. Future studies have to be designed in ways that permit clinically meaningful subdivision of the patients' and the therapists' decisions for premature termination.

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

PubMed

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

Predicting Survival From Large Echocardiography and Electronic Health Record Datasets: Optimization With Machine Learning.

PubMed

Samad, Manar D; Ulloa, Alvaro; Wehner, Gregory J; Jing, Linyuan; Hartzel, Dustin; Good, Christopher W; Williams, Brent A; Haggerty, Christopher M; Fornwalt, Brandon K

2018-06-09

The goal of this study was to use machine learning to more accurately predict survival after echocardiography. Predicting patient outcomes (e.g., survival) following echocardiography is primarily based on ejection fraction (EF) and comorbidities. However, there may be significant predictive information within additional echocardiography-derived measurements combined with clinical electronic health record data. Mortality was studied in 171,510 unselected patients who underwent 331,317 echocardiograms in a large regional health system. We investigated the predictive performance of nonlinear machine learning models compared with that of linear logistic regression models using 3 different inputs: 1) clinical variables, including 90 cardiovascular-relevant International Classification of Diseases, Tenth Revision, codes, and age, sex, height, weight, heart rate, blood pressures, low-density lipoprotein, high-density lipoprotein, and smoking; 2) clinical variables plus physician-reported EF; and 3) clinical variables and EF, plus 57 additional echocardiographic measurements. Missing data were imputed with a multivariate imputation by using a chained equations algorithm (MICE). We compared models versus each other and baseline clinical scoring systems by using a mean area under the curve (AUC) over 10 cross-validation folds and across 10 survival durations (6 to 60 months). Machine learning models achieved significantly higher prediction accuracy (all AUC >0.82) over common clinical risk scores (AUC = 0.61 to 0.79), with the nonlinear random forest models outperforming logistic regression (p < 0.01). The random forest model including all echocardiographic measurements yielded the highest prediction accuracy (p < 0.01 across all models and survival durations). Only 10 variables were needed to achieve 96% of the maximum prediction accuracy, with 6 of these variables being derived from echocardiography. Tricuspid regurgitation velocity was more predictive of survival than LVEF. In a subset of studies with complete data for the top 10 variables, multivariate imputation by chained equations yielded slightly reduced predictive accuracies (difference in AUC of 0.003) compared with the original data. Machine learning can fully utilize large combinations of disparate input variables to predict survival after echocardiography with superior accuracy. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Probabilistic Gait Classification in Children with Cerebral Palsy: A Bayesian Approach

ERIC Educational Resources Information Center

Van Gestel, Leen; De Laet, Tinne; Di Lello, Enrico; Bruyninckx, Herman; Molenaers, Guy; Van Campenhout, Anja; Aertbelien, Erwin; Schwartz, Mike; Wambacq, Hans; De Cock, Paul; Desloovere, Kaat

2011-01-01

Three-dimensional gait analysis (3DGA) generates a wealth of highly variable data. Gait classifications help to reduce, simplify and interpret this vast amount of 3DGA data and thereby assist and facilitate clinical decision making in the treatment of CP. CP gait is often a mix of several clinically accepted distinct gait patterns. Therefore,…

[Prevalence and factors associated with peripheral artery disease in patients with type 2 diabetes mellitus in Primary Care].

PubMed

Montero-Monterroso, J L; Gascón-Jiménez, J A; Vargas-Rubio, M D; Quero-Salado, C; Villalba-Marín, P; Pérula-de Torres, L A

2015-01-01

Peripheral artery disease in the lower limbs (PAD) is a prevalent condition that entails high morbidity in diabetic patients; this study assesses PAD in these patients and its socio-demographic and clinic associated variables. Descriptive study in a systematic sample of diabetic patients (DM2) aged 50-80 years, in Primary Care settings. The dependent variable was the presence of PAD diagnosed by ankle-brachial index (ABI) ≤ 0.9; independent variables: socio-demographic, clinical and laboratory. bivariate and multiple logistic regression analyses were performed to determine the variables associated with low ABI. A sample of 251 patients, 52.6% women; mean age: 68.5 ±8.5. A low ABI was detected in 18.3% (95% Confidence Interval (95% CI):13.3-23.3%), with 6 subjets (2.4%) previously diagnosed as suffering PAD. Age (OR=1.07; 95% CI: 1.02-1.12) and retinopathy (OR=2.69; 95% CI: 1.06-6.81) were associated (multiple logistic regression analysis) with ABI. The percentage of patients diagnosed with PAD is very low, although PAD prevalence is high among DM2 patients attending Primary Care clinics, especially in older patients and those with retinopathy. We emphasize the recommendation of performing the ABI test in this population at risk. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid.

PubMed

Altman, Roy D; Schemitsch, Emil; Bedi, Asheesh

2015-10-01

Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who are utilizing these guidelines are making their clinical decisions on the best available evidence. At present, the inconsistent recommendations provided for intra-articular hyaluronic acid treatment make it difficult for clinical professionals to determine its appropriateness when treating patients with knee osteoarthritis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR.

PubMed

Sandén, Per; Renlund, Henrik; Svensson, Peter J; Själander, Anders

2017-01-05

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

Aligning clinical compensation with clinical productivity: design and implementation of the financial value unit (FVU) system in an academic department of internal medicine.

PubMed

Stites, Steven; Steffen, Patrick; Turner, Scott; Pingleton, Susan

2013-07-01

A new metric was developed and implemented at the University of Kansas School of Medicine Department of Internal Medicine, the financial value unit (FVU). This metric analyzes faculty clinical compensation compared with clinical work productivity as a transparent means to decrease the physician compensation variability and compensate faculty equitably for clinical work.The FVU is the ratio of individual faculty clinical compensation compared with their total work relative value units (wRVUs) generated divided by Medical Group Management Association (MGMA) salary to wRVUs of a similar MGMA physician.The closer the FVU ratio is to 1.0, the closer clinical compensation is to that of an MGMA physician with similar clinical productivity. Using FVU metrics to calculate a faculty salary gap compared with MGMA median salary and wRVU productivity, a divisional production payment was established annually.From FY 2006 to FY 2011, both total faculty numbers and overall clinical activity increased. With the implementation of the FVU, both clinical productivity and compensation increased while, at the same time, physician retention rates remained high. Variability in physician compensation decreased. Dramatic clinical growth was associated with the alignment of clinical work and clinical compensation in a transparent and equable process.

Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.

PubMed

Clark, S R; Baune, B T; Schubert, K O; Lavoie, S; Smesny, S; Rice, S M; Schäfer, M R; Benninger, F; Feucht, M; Klier, C M; McGorry, P D; Amminger, G P

2016-09-20

Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview.

Closed treatment of unilateral mandibular condyle fractures in adults: a systematic review.

PubMed

Rozeboom, A V J; Dubois, L; Bos, R R M; Spijker, R; de Lange, J

2017-04-01

Of all mandibular fractures, 25-35% are condylar. Many studies have focused on whether to treat such fractures via open or closed modalities. A uniform protocol for closed treatment is lacking, but such a protocol could ensure good clinical practice. The aims of this systematic review were to provide an overview of the published studies exclusively pertaining to closed treatment and to summarize the existing modalities for closed treatment and their clinical outcomes. Sixteen studies were selected for detailed analysis. The treatments given were highly variable, ranging from doing nothing to applying maxillomandibular fixation with stainless steel wires. The results of the different studies and the treatment modalities used were difficult to interpret; however no clear differences in the outcome measures were seen between the treatment modalities applied. Complications encountered after closed treatment included malocclusion, limited mouth opening, reduced range of motion, and persistent pain. Due to the heterogeneity between groups, high loss-to-follow-up, poor descriptions of the treatments given, and variability in outcome measurement methods, no clear associations between adverse outcomes and the treatments applied could be determined. This review suggests that due to the high level of methodological variability in the relevant studies published to date, there are currently no uniform standards for the closed treatment of condylar fractures that can be expected to yield good clinical results. The establishment of such standards could potentially improve treatment outcomes. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Young, Julia M; Morgan, Benjamin R; Mišić, Bratislav; Schweizer, Tom A; Ibrahim, George M; Macdonald, R Loch

2015-12-01

Individuals who have aneurysmal subarachnoid hemorrhages (SAHs) experience decreased health-related qualities of life (HRQoLs) that persist after the primary insult. To identify clinical variables that concurrently associate with HRQoL outcomes by using a partial least-squares approach, which has the distinct advantage of explaining multidimensional variance where predictor variables may be highly collinear. Data collected from the CONSCIOUS-1 trial was used to extract 29 clinical variables including SAH presentation, hospital procedures, and demographic information in addition to 5 HRQoL outcome variables for 256 individuals. A partial least-squares analysis was performed by calculating a heterogeneous correlation matrix and applying singular value decomposition to determine components that best represent the correlations between the 2 sets of variables. Bootstrapping was used to estimate statistical significance. The first 2 components accounting for 81.6% and 7.8% of the total variance revealed significant associations between clinical predictors and HRQoL outcomes. The first component identified associations between disability in self-care with longer durations of critical care stay, invasive intracranial monitoring, ventricular drain time, poorer clinical grade on presentation, greater amounts of cerebral spinal fluid drainage, and a history of hypertension. The second component identified associations between disability due to pain and discomfort as well as anxiety and depression with greater body mass index, abnormal heart rate, longer durations of deep sedation and critical care, and higher World Federation of Neurosurgical Societies and Hijdra scores. By applying a data-driven, multivariate approach, we identified robust associations between SAH clinical presentations and HRQoL outcomes. EQ-VAS, EuroQoL visual analog scaleHRQoL, health-related quality of lifeICU, intensive care unitIVH, intraventricular hemorrhagePLS, partial least squaresSAH, subarachnoid hemorrhageSVD, singular value decompositionWFNS, World Federation of Neurosurgical Societies.

HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

PubMed

Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

2015-10-01

INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and transmission or clinical progression, although the proportion of deaths was higher for subtype B. Among those who died during the study period, there were no differences between subtypes in the mean time from HIV or AIDS diagnosis to death. CONCLUSIONS Our results suggest that B and non-B HIV-1 subtypes found in Cuba do not differ in transmissibility and in clinical disease progression. KEYWORDS HIV-1, AIDS, molecular epidemiology, transmissibility, clinical progression, subtypes, circulating recombinant forms, pathogenesis, Cuba.

High-resolution copy number variation analysis of schizophrenia in Japan.

PubMed

Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

2017-03-01

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10 -9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

PubMed

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

The distribution of outcomes research papers across clinical journals.

PubMed

Goldsack, Jennifer; McLaughlin, Chris; Bristol, Mirar N; Loeb, Alex; Bergey, Meredith; Sonnad, Seema S

2011-06-01

This study examines the distribution of health outcomes research (HOR) studies in the clinical literature by clinical areas and journal impact factor. The authors reviewed 535 journals and divided the sample into higher and lower impact journals across four clinical area. Mann-Whitney and Kruskal-Wallis tests were used to examine differences across four categories of outcomes research articles published, specifically the incidence of articles in higher versus lower impact journals and differences across clinical areas. All high-impact journals published more safety and quality articles than process assessment, quality of life, or cost analysis studies. The number of each type of outcomes research study published was highly variable across all clinical areas. Only arthritis and outcomes research journals showed statistically significant differences between higher versus lower impact journals. Authors may benefit from considering these differences in their clinical specialty area when deciding where to submit HOR studies.

Team clinician variability in return-to-play decisions.

PubMed

Shultz, Rebecca; Bido, Jennifer; Shrier, Ian; Meeuwisse, Willem H; Garza, Daniel; Matheson, Gordon O

2013-11-01

To describe the variability in the return-to-play (RTP) decisions of experienced team clinicians and to assess their clinical opinion as to the relevance of 19 factors described in a RTP decision-making model. Survey questionnaire. Advanced Team Physician Course. Sixty-seven of 101 sports medicine clinicians completed the questionnaire. Results were analyzed using descriptive statistics. For categorical variables, we report percentage and frequency. For continuous variables, we report mean (SD) if data were approximately normally distributed and frequencies for clinically relevant categories for skewed data. The average number of years of clinical sports medicine experience was 13.6 (9.8). Of the 62 clinicians who responded fully, 35% (n = 22) would "clear" (vs "not clear") an athlete to participate in sport even if the risk of an acute reinjury or long-term sequelae is increased. When respondents were given 6 different RTP options rather than binary choices, there were increased discrepancies across some injury risk scenarios. For example, 8.1% to 16.1% of respondents who chose to clear an athlete when presented with binary choices, later chose to "not clear" an athlete when given 6 graded RTP options. The respondents often considered factors of potential importance to athletes as nonimportant to the RTP decision process if risk of reinjury was unaffected (range, n = 4 [10%] to n = 19 [45%]). There is a high degree of variability in how different clinicians weight the different factors related to RTP decision making. More precise definitions decrease but do not eliminate this variability.

Night-to-Night Sleep Variability in Older Adults With Chronic Insomnia: Mediators and Moderators in a Randomized Controlled Trial of Brief Behavioral Therapy (BBT-I)

PubMed Central

Chan, Wai Sze; Williams, Jacob; Dautovich, Natalie D.; McNamara, Joseph P.H.; Stripling, Ashley; Dzierzewski, Joseph M.; Berry, Richard B.; McCoy, Karin J.M.; McCrae, Christina S.

2017-01-01

Study Objectives: Sleep variability is a clinically significant variable in understanding and treating insomnia in older adults. The current study examined changes in sleep variability in the course of brief behavioral therapy for insomnia (BBT-I) in older adults who had chronic insomnia. Additionally, the current study examined the mediating mechanisms underlying reductions of sleep variability and the moderating effects of baseline sleep variability on treatment responsiveness. Methods: Sixty-two elderly participants were randomly assigned to either BBT-I or self-monitoring and attention control (SMAC). Sleep was assessed by sleep diaries and actigraphy from baseline to posttreatment and at 3-month follow-up. Mixed models were used to examine changes in sleep variability (within-person standard deviations of weekly sleep parameters) and the hypothesized mediation and moderation effects. Results: Variabilities in sleep diary-assessed sleep onset latency (SOL) and actigraphy-assessed total sleep time (TST) significantly decreased in BBT-I compared to SMAC (Pseudo R2 = .12, .27; P = .018, .008). These effects were mediated by reductions in bedtime and wake time variability and time in bed. Significant time × group × baseline sleep variability interactions on sleep outcomes indicated that participants who had higher baseline sleep variability were more responsive to BBT-I; their actigraphy-assessed TST, SOL, and sleep efficiency improved to a greater degree (Pseudo R2 = .15 to .66; P < .001 to .044). Conclusions: BBT-I is effective in reducing sleep variability in older adults who have chronic insomnia. Increased consistency in bedtime and wake time and decreased time in bed mediate reductions of sleep variability. Baseline sleep variability may serve as a marker of high treatment responsiveness to BBT-I. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT02967185 Citation: Chan WS, Williams J, Dautovich ND, McNamara JP, Stripling A, Dzierzewski JM, Berry RB, McCoy KJ, McCrae CS. Night-to-night sleep variability in older adults with chronic insomnia: mediators and moderators in a randomized controlled trial of brief behavioral therapy (BBT-I). J Clin Sleep Med. 2017;13(11):1243–1254. PMID:28992829

A population-based study of demographical variables and ability to perform activities of daily living in adults with osteogenesis imperfecta.

PubMed

Wekre, Lena Lande; Frøslie, Kathrine Frey; Haugen, Lena; Falch, Jan A

2010-01-01

To describe demographical variables, and to study functional ability to perform activities of daily life in adults with osteogenesis imperfecta (OI). Population-based study. Ninety-seven patients aged 25 years and older, 41 men and 56 women, were included. For the demographical variables, comparison was made to a matched control-group (475 persons) from the Norwegian general population. Structured interviews concerning social conditions, employment and educational issues and clinical examination were performed. The Sunnaas Activities of Daily Living (ADL) Index was used to assess the ability to perform ADL. The prevalence of clinical manifestations according to Sillence was in accordance with other studies. Demographical variables showed that most adults with OI are married and have children. They had a higher educational level than the control group, but the employment rate was significantly lower. However, the rate of employed men was similar in both groups. Adult persons with OI achieved a high score when tested for ADL. Adults with OI are well educated compared with the general population, and most of them are employed. High scores when tested for ADL indicate that most of them are able to live their lives independently, even though there are some differences according to the severity of the disorder.

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

Low heart rate variability in patients with clinical burnout.

PubMed

Lennartsson, Anna-Karin; Jonsdottir, Ingibjörg; Sjörs, Anna

2016-12-01

Several studies have shown that acute psychosocial stress and chronic psychosocial stress reduce heart rate variability (HRV). It is likely that individuals suffering from burnout have reduced HRV, as a consequence of the long-term stress exposure. This study investigated HRV in 54 patients with clinical burnout (40 women and 14 men) and in 55 individuals reporting low burnout scores (healthy; 24 women and 31 men) and 52 individuals reporting high burnout scores (non-clinical burnout; 33 women and 19 men). The participants underwent a 300s ECG recording in the supine position. Standard deviation of normal R-R intervals (SDNN) and the root mean square of successive normal interval differences (RMSSD) were derived from time domain HRV analysis. Frequency domain HRV measures; total power (TP), low frequency power (LF), high frequency power (HF), and LF/HF ratio were calculated. All HRV measures, except LF/HF ratio, were lower in the clinical burnout patients compared to both the non-clinical burnout group and the healthy group. The difference was larger between the patients and the healthy group than between the patients and the non-clinical burnout group. HRV did not differ significantly between the non-clinical burnout group and the healthy group. Low HRV in burnout patients may constitute one of the links to associated adverse health, since low HRV reflects low parasympathetic activity - and accordingly low anabolic/regenerative activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Stress-based animal models of depression: Do we actually know what we are doing?

PubMed

Yin, Xin; Guven, Nuri; Dietis, Nikolas

2016-12-01

Depression is one of the leading causes of disability and a significant health-concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them. Only few studies have reported how minor modifications of these parameters affect the model phenotype. Thus, the existing variability in how these models are used has been a strong barrier for drug development as well as benchmark and evaluation of these pre-clinical models of depression. It also has been the source of confusing variability in the experimental outcomes between research groups using the same models. In this review, we summarize the known variability in the experimental protocols, identify the main and relevant parameters for each model and describe the variable values using characteristic examples. Our view of depression and our efforts to discover novel and effective antidepressants is largely based on our detailed knowledge of these testing paradigms, and requires a sound understanding around the importance of individual parameters to optimize and improve these pre-clinical models. Copyright © 2016 Elsevier B.V. All rights reserved.

VTE Risk assessment - a prognostic Model: BATER Cohort Study of young women.

PubMed

Heinemann, Lothar Aj; Dominh, Thai; Assmann, Anita; Schramm, Wolfgang; Schürmann, Rolf; Hilpert, Jan; Spannagl, Michael

2005-04-18

BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18-55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 104 WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool - containing clinical information (and if available also genetic data) - seems to be worthwhile testing in medical practice in order to confirm or refute the positive findings of this study. Our cohort study will be continued to include more VTE cases and to increase predictive value of the model.

Pseudomonas aeruginosa clinical and environmental isolates constitute a single population with high phenotypic diversity

PubMed Central

2014-01-01

Background Pseudomonas aeruginosa is an opportunistic pathogen with a high incidence of hospital infections that represents a threat to immune compromised patients. Genomic studies have shown that, in contrast to other pathogenic bacteria, clinical and environmental isolates do not show particular genomic differences. In addition, genetic variability of all the P. aeruginosa strains whose genomes have been sequenced is extremely low. This low genomic variability might be explained if clinical strains constitute a subpopulation of this bacterial species present in environments that are close to human populations, which preferentially produce virulence associated traits. Results In this work, we sequenced the genomes and performed phenotypic descriptions for four non-human P. aeruginosa isolates collected from a plant, the ocean, a water-spring, and from dolphin stomach. We show that the four strains are phenotypically diverse and that this is not reflected in genomic variability, since their genomes are almost identical. Furthermore, we performed a detailed comparative genomic analysis of the four strains studied in this work with the thirteen previously reported P. aeruginosa genomes by means of describing their core and pan-genomes. Conclusions Contrary to what has been described for other bacteria we have found that the P. aeruginosa core genome is constituted by a high proportion of genes and that its pan-genome is thus relatively small. Considering the high degree of genomic conservation between isolates of P. aeruginosa from diverse environments, including human tissues, some implications for the treatment of infections are discussed. This work also represents a methodological contribution for the genomic study of P. aeruginosa, since we provide a database of the comparison of all the proteins encoded by the seventeen strains analyzed. PMID:24773920

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

The Relationship of Clinical Nurses' Perceptions of Structural and Psychological Empowerment and Engagement on Their Unit.

PubMed

DiNapoli, Jean Marie; O'Flaherty, Deirdre; Musil, Carol; Clavelle, Joanne T; Fitzpatrick, Joyce J

2016-02-01

The purpose of this study was to describe relationships between structural empowerment, psychological empowerment, and engagement among clinical nurses. Empowerment and engagement are key drivers of retention and quality in healthcare. Creating an empowering culture and an engaged staff supports initiatives that are essential for positive work environments. A survey of 280 nurses in a national conference was conducted using the Conditions of Work Effectiveness, Psychological Empowerment Instrument, and the Utrecht Work Engagement Scale. Pearson correlation coefficients and multiple regression analysis were used to determine relationships between demographic data and study variables. Overall, nurses had high perceptions of structural empowerment and psychological empowerment and were moderately engaged. Also, significant positive relationships were found between the key study variables. Results show positive correlations between empowerment and perceived engagement among clinical nurses.

[Pulmonary involvement in connective tissue disease].

PubMed

Bartosiewicz, Małgorzata

2016-01-01

The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

Effect of task-oriented training and high-variability practice on gross motor performance and activities of daily living in children with spastic diplegia.

PubMed

Kwon, Hae-Yeon; Ahn, So-Yoon

2016-10-01

[Purpose] This study investigates how a task-oriented training and high-variability practice program can affect the gross motor performance and activities of daily living for children with spastic diplegia and provides an effective and reliable clinical database for future improvement of motor performances skills. [Subjects and Methods] This study randomly assigned seven children with spastic diplegia to each intervention group including that of a control group, task-oriented training group, and a high-variability practice group. The control group only received neurodevelopmental treatment for 40 minutes, while the other two intervention groups additionally implemented a task-oriented training and high-variability practice program for 8 weeks (twice a week, 60 min per session). To compare intra and inter-relationships of the three intervention groups, this study measured gross motor performance measure (GMPM) and functional independence measure for children (WeeFIM) before and after 8 weeks of training. [Results] There were statistically significant differences in the amount of change before and after the training among the three intervention groups for the gross motor performance measure and functional independence measure. [Conclusion] Applying high-variability practice in a task-oriented training course may be considered an efficient intervention method to improve motor performance skills that can tune to movement necessary for daily livelihood through motor experience and learning of new skills as well as change of tasks learned in a complex environment or similar situations to high-variability practice.

Understanding the role of argininosuccinate lyase transcript variants in the clinical and biochemical variability of the urea cycle disorder argininosuccinic aciduria.

PubMed

Hu, Liyan; Pandey, Amit V; Eggimann, Sandra; Rüfenacht, Véronique; Möslinger, Dorothea; Nuoffer, Jean-Marc; Häberle, Johannes

2013-11-29

Argininosuccinic aciduria (ASA) is an autosomal recessive urea cycle disorder caused by deficiency of argininosuccinate lyase (ASL) with a wide clinical spectrum from asymptomatic to severe hyperammonemic neonatal onset life-threatening courses. We investigated the role of ASL transcript variants in the clinical and biochemical variability of ASA. Recombinant proteins for ASL wild type, mutant p.E189G, and the frequently occurring transcript variants with exon 2 or 7 deletions were (co-)expressed in human embryonic kidney 293T cells. We found that exon 2-deleted ASL forms a stable truncated protein with no relevant activity but a dose-dependent dominant negative effect on enzymatic activity after co-expression with wild type or mutant ASL, whereas exon 7-deleted ASL is unstable but seems to have, nevertheless, a dominant negative effect on mutant ASL. These findings were supported by structural modeling predictions for ASL heterotetramer/homotetramer formation. Illustrating the physiological relevance, the predominant occurrence of exon 7-deleted ASL was found in two patients who were both heterozygous for the ASL mutant p.E189G. Our results suggest that ASL transcripts can contribute to the highly variable phenotype in ASA patients if expressed at high levels. Especially, the exon 2-deleted ASL variant may form a heterotetramer with wild type or mutant ASL, causing markedly reduced ASL activity.

Social gradients in periodontal diseases among adolescents.

PubMed

López, Rodrigo; Fernández, Olaya; Baelum, Vibeke

2006-06-01

To investigate the association between socioeconomic position and periodontal diseases among adolescents. Data were obtained from 9203 Chilean high school students. Clinical examinations included direct recordings of clinical attachment level and the necrotizing ulcerative gingival lesions. Students answered a questionnaire on various dimensions of socioeconomic position. Seven periodontal outcomes were analyzed. Logistic regression analyses were used to identify socioeconomic variables associated with the periodontal outcomes. The occurrence of all periodontal outcomes investigated followed social gradients, and paternal income and parental education were the most influential variables. The study demonstrates the existence of significant social gradients in periodontal diseases already among adolescents. This is worrying, and indicates a new potential for further insight into the mechanisms of periodontal disease causation.

Explaining variability in first grazing season heifer growth combining individually measured parasitological and clinical indicators with exposure to gastrointestinal nematode infection based on grazing management practice.

PubMed

Merlin, Aurélie; Chauvin, Alain; Madouasse, Aurélien; Froger, Sébastien; Bareille, Nathalie; Chartier, Christophe

2016-07-30

The objective of our study was to explain the variability of average daily weight gain (ADWG) due to gastrointestinal nematode (GIN) infection for 291 non treated first grazing season (FGS) heifers, from 12 independent groups in the western part of France, by combining parasitological and clinical indicators at individual level and grazing management indicators at group level. Parasitological indicators were faecal egg count (FEC), anti Ostertagia ostertagi antibody level (Ostertagia ODR), and pepsinogen level. Clinical indicators were diarrhea score (DISCO) and breech soiling score (BSS). At group level, grazing management practice (GMP), based on three variables (supplementation, month of turnout, grazing season duration), was clustered into three categories reflecting low, medium or high exposure (EXP) to GIN. Depending on the groups, turnout was from mid-March to early July and housing was from mid-October to late November, with a FGS duration ranging from 4 to 8.4 months. At turnout, the mean age of heifers was 8 months (range: 6-16 months) and they weighed between 175 and 268kg. In each GMP category, FEC significantly decreased between the mid-season and the housing, while Ostertagia ODR and pepsinogen level increased gradually throughout the grazing season. In contrast, clinical indicators did not show any seasonal variation. In a multivariate linear model, 22% of the ADWG variability was significantly explained by two individual indicators (Ostertagia ODR: 12.6%, DISCO: 4.8%) and by the group indicator (GMP category: 4.8%). ADWG losses due to GIN exposure (Ostertagia ODR) were estimated up to 39kg per heifer for the overall grazing season. For groups within the low EXP category the difference between animals with low (<697g/day) or high (>697g/day) ADWG was explained by the clinical indicator DISCO. In contrast, for groups within the medium and high EXP categories this difference was explained by a parasitological indicator (Ostertagia ODR). This study highlighted the value of combining both grazing management (group level) and parasitological (individual level) indicators to assess the impact of GIN on ADWG of FGS heifers. As a result, this combination might allow a better discrimination of animals or groups that may be in need of treatment in a targeting selective treatment approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Variability of the institutional review board process within a national research network.

PubMed

Khan, Muhammad A; Barratt, Michelle S; Krugman, Scott D; Serwint, Janet R; Dumont-Driscoll, Marilyn

2014-06-01

To determine the variability of the institutional review board (IRB) process for a minimal risk multicenter study. Participants included 24 Continuity Research Network (CORNET) sites of the Academic Pediatric Association that participated in a cross-sectional study. Each site obtained individual institutional IRB approval. An anonymous questionnaire went to site investigators about the IRB process at their institution. Twenty-two of 24 sites (92%) responded. Preparation time ranged from 1 to 20 hours, mean of 7.1 hours. Individuals submitting ≤3 IRB applications/year required more time for completion than those submitting >3/year (P < .05). Thirteen of 22 (59%) study sites received approval with "exempt" status, and 6 (27%) approved as "expedited" studies. IRB experiences were highly variable across study sites. These findings indicate that multicenter research projects should anticipate barriers to timely study implementation. Improved IRB standardization or centralization for multicenter clinical studies would facilitate this type of practice-based clinical research.

Mental models of audit and feedback in primary care settings.

PubMed

Hysong, Sylvia J; Smitham, Kristen; SoRelle, Richard; Amspoker, Amber; Hughes, Ashley M; Haidet, Paul

2018-05-30

Audit and feedback has been shown to be instrumental in improving quality of care, particularly in outpatient settings. The mental model individuals and organizations hold regarding audit and feedback can moderate its effectiveness, yet this has received limited study in the quality improvement literature. In this study we sought to uncover patterns in mental models of current feedback practices within high- and low-performing healthcare facilities. We purposively sampled 16 geographically dispersed VA hospitals based on high and low performance on a set of chronic and preventive care measures. We interviewed up to 4 personnel from each location (n = 48) to determine the facility's receptivity to audit and feedback practices. Interview transcripts were analyzed via content and framework analysis to identify emergent themes. We found high variability in the mental models of audit and feedback, which we organized into positive and negative themes. We were unable to associate mental models of audit and feedback with clinical performance due to high variance in facility performance over time. Positive mental models exhibit perceived utility of audit and feedback practices in improving performance; whereas, negative mental models did not. Results speak to the variability of mental models of feedback, highlighting how facilities perceive current audit and feedback practices. Findings are consistent with prior research  in that variability in feedback mental models is associated with lower performance.; Future research should seek to empirically link mental models revealed in this paper to high and low levels of clinical performance.

High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves

PubMed Central

Angstman, Nicholas B.; Kiessling, Maren C.; Frank, Hans-Georg; Schmitz, Christoph

2015-01-01

In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI. PMID:25705183

PCR-RFLP of ribosomal internal transcribed spacers highlights inter and intra-species variation among Leishmania strains native to La Paz, Bolivia.

PubMed

Buitrago, Rosio; Cupolillo, Elisa; Bastrenta, Brigitte; Le Pont, Francois; Martinez, Eddy; Barnabé, Christian; Brenière, Simone Frédérique

2011-04-01

Human leishmaniasis is highly endemic in Bolivia and shows a growing incidence. This report reveals the genetic variability of 35 isolates mainly belonging to Leishmania braziliensis and Leishmania amazonensis species. Among them, 31 were from human patients with different clinical presentations, 3 strains from Lutzomya nuneztovari anglesi (the proven vector of L. amazonensis) and 1 strain of a mammal (Conepatus chinga). The isolates were analyzed by isoenzyme electrophoresis (MLEE) and PCR-RFLP of ITS rRNA genes, a genetic marker highly polymorphic and better adapted to sub-structuring of populations. MLEE and RFLP-ITS were in agreement to discriminate the species, 12 belong to L. (V.) braziliensis, 21 to L. (L.) amazonensis, 1 to Leishmania (V.) lainsoni and 1 to Leishmania (L.) chagasi. Among L. (V.) braziliensis the RFLP-ITS only highlights variability. Ten isolates from either cutaneous or mucocutaneous clinical forms, were grouped together (bootstrap value of 99.8%) apart from two others, one from a mammal (C. chinga), the other from a patient with a cutaneous form. Among L. (L.) amazonensis both markers detect variability but no significant sub-division was identified including isolates from different clinical forms. Moreover, the high frequency of several isolates from cutaneous forms occurred during an outbreak, with putative hybrid character (multiloci heterozygous patterns depicted by MLEE) could be linked to better fitness of these parasites. However, in the absence of observation of hypothetical parents, their hybrid status remains a question. Copyright © 2010. Published by Elsevier B.V.

Anxiety, Depression and Hopelessness in Adolescents: A Structural Equation Model

PubMed Central

Cunningham, Shaylyn; Gunn, Thelma; Alladin, Assen; Cawthorpe, David

2008-01-01

Objective This study tested a structural model, examining the relationship between a latent variable termed demoralization and measured variables (anxiety, depression and hopelessness) in a community sample of Canadian youth. Methods The combined sample consisted of data collected from four independent studies from 2001 to 2005. Nine hundred and seventy one (n=971) participants were high school students (grades 10–12) from three geographic locations: Calgary, Saskatchewan and Lethbridge. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory-Revised (BDI-II), Beck Hopelessness Scale (BHS), and demographic survey. Structural equation modeling was used for statistical analysis. Results The analysis revealed that the final model, including depression, anxiety and hopelessness and one latent variable demoralization, fit the data (chi-square value, X2 (2) = 7.25, p< .001, goodness of fit indices (CFI=0.99, NFI=0.98) and standardized error (0.05). Overall, the findings suggest that close relationships exist among depression, anxiety, hopelessness and demoralization that is stable across demographic variables. Further, the model explains the relationship between sub-clinical anxiety, depression and hopelessness. Conclusion These findings contribute to a theoretical framework, which has implications for educational and clinical intervention. The present findings will help guide further preventative research on examining demoralization as a precursor to sub-clinical anxiety and depression. PMID:18769644

Retrospective cohort study of the clinical performance of 1-stage dental implants.

PubMed

Carr, Alan B; Choi, Yong-Geun; Eckert, Steven E; Desjardins, Ronald P

2003-01-01

To evaluate long-term clinical performance of 1-stage dental implant prostheses at a single clinic, emphasizing clinical and demographic characteristics that affect implant survival. Dental records of all 308 patients (674 implants) treated with 1-stage implants at Mayo Clinic from October 1993 through May 2000 were reviewed from implant placement to last visit. Exposure and outcome variables affecting performance were collected separately to control bias in the data collection process. Additional confounding factors (age and sex) were adjusted with the stratified Cox proportional hazards model. Implant survival was determined by means of a Kaplan-Meier survival estimate. The log-rank test was used to determine the role of clinical and demographic variables in implant survival. The relative risk associated with the possible effect of clinical and demographic variables on implant survival was estimated with the Cox proportional hazards model. The implant survival rate (n = 654 implants) was 97% (mean +/- SD follow-up, 21.0 +/- 18.8 months; range, 1 to 78 months). Performance bias was limited because nearly all patients were treated by 1 prosthodontist. Two implants failed after loading (6 and 9 months). The incidence of complications was less than 4%. Among the implant failures, use of heterogeneous bone graft was associated with 4.8 times more failures than was use of autogenous bone graft (P = .04). After augmentation, delaying implant placement for 5 to 6 months resulted in 8.6 times more failures than the rate after earlier placement (P < .001). Retrospective review of the clinical performance of a 1-stage dental implant system yielded a 97% survival rate, with no failures noted after 13 months. Prosthetic complications were low, especially for fixed implant prostheses. Clinical performance of 1-stage dental implant prostheses between 1993 and 2000 demonstrated a high level of predictability.

Assessing data quality and the variability of source data verification auditing methods in clinical research settings.

PubMed

Houston, Lauren; Probst, Yasmine; Martin, Allison

2018-05-18

Data audits within clinical settings are extensively used as a major strategy to identify errors, monitor study operations and ensure high-quality data. However, clinical trial guidelines are non-specific in regards to recommended frequency, timing and nature of data audits. The absence of a well-defined data quality definition and method to measure error undermines the reliability of data quality assessment. This review aimed to assess the variability of source data verification (SDV) auditing methods to monitor data quality in a clinical research setting. The scientific databases MEDLINE, Scopus and Science Direct were searched for English language publications, with no date limits applied. Studies were considered if they included data from a clinical trial or clinical research setting and measured and/or reported data quality using a SDV auditing method. In total 15 publications were included. The nature and extent of SDV audit methods in the articles varied widely, depending upon the complexity of the source document, type of study, variables measured (primary or secondary), data audit proportion (3-100%) and collection frequency (6-24 months). Methods for coding, classifying and calculating error were also inconsistent. Transcription errors and inexperienced personnel were the main source of reported error. Repeated SDV audits using the same dataset demonstrated ∼40% improvement in data accuracy and completeness over time. No description was given in regards to what determines poor data quality in clinical trials. A wide range of SDV auditing methods are reported in the published literature though no uniform SDV auditing method could be determined for "best practice" in clinical trials. Published audit methodology articles are warranted for the development of a standardised SDV auditing method to monitor data quality in clinical research settings. Copyright © 2018. Published by Elsevier Inc.

Relations between mental health team characteristics and work role performance.

PubMed

Fleury, Marie-Josée; Grenier, Guy; Bamvita, Jean-Marie; Farand, Lambert

2017-01-01

Effective mental health care requires a high performing, interprofessional team. Among 79 mental health teams in Quebec (Canada), this exploratory study aims to 1) determine the association between work role performance and a wide range of variables related to team effectiveness according to the literature, and to 2) using structural equation modelling, assess the covariance between each of these variables as well as the correlation with other exogenous variables. Work role performance was measured with an adapted version of a work role questionnaire. Various independent variables including team manager characteristics, user characteristics, team profiles, clinical activities, organizational culture, network integration strategies and frequency/satisfaction of interactions with other teams or services were analyzed under the structural equation model. The later provided a good fit with the data. Frequent use of standardized procedures and evaluation tools (e.g. screening and assessment tools for mental health disorders) and team manager seniority exerted the most direct effect on work role performance. While network integration strategies had little effect on work role performance, there was a high covariance between this variable and those directly affecting work role performance among mental health teams. The results suggest that the mental healthcare system should apply standardized procedures and evaluation tools and, to a lesser extent, clinical approaches to improve work role performance in mental health teams. Overall, a more systematic implementation of network integration strategies may contribute to improved work role performance in mental health care.

Teaching a Machine to Feel Postoperative Pain: Combining High-Dimensional Clinical Data with Machine Learning Algorithms to Forecast Acute Postoperative Pain

PubMed Central

Tighe, Patrick J.; Harle, Christopher A.; Hurley, Robert W.; Aytug, Haldun; Boezaart, Andre P.; Fillingim, Roger B.

2015-01-01

Background Given their ability to process highly dimensional datasets with hundreds of variables, machine learning algorithms may offer one solution to the vexing challenge of predicting postoperative pain. Methods Here, we report on the application of machine learning algorithms to predict postoperative pain outcomes in a retrospective cohort of 8071 surgical patients using 796 clinical variables. Five algorithms were compared in terms of their ability to forecast moderate to severe postoperative pain: Least Absolute Shrinkage and Selection Operator (LASSO), gradient-boosted decision tree, support vector machine, neural network, and k-nearest neighbor, with logistic regression included for baseline comparison. Results In forecasting moderate to severe postoperative pain for postoperative day (POD) 1, the LASSO algorithm, using all 796 variables, had the highest accuracy with an area under the receiver-operating curve (ROC) of 0.704. Next, the gradient-boosted decision tree had an ROC of 0.665 and the k-nearest neighbor algorithm had an ROC of 0.643. For POD 3, the LASSO algorithm, using all variables, again had the highest accuracy, with an ROC of 0.727. Logistic regression had a lower ROC of 0.5 for predicting pain outcomes on POD 1 and 3. Conclusions Machine learning algorithms, when combined with complex and heterogeneous data from electronic medical record systems, can forecast acute postoperative pain outcomes with accuracies similar to methods that rely only on variables specifically collected for pain outcome prediction. PMID:26031220

Relations between mental health team characteristics and work role performance

PubMed Central

Grenier, Guy; Bamvita, Jean-Marie; Farand, Lambert

2017-01-01

Effective mental health care requires a high performing, interprofessional team. Among 79 mental health teams in Quebec (Canada), this exploratory study aims to 1) determine the association between work role performance and a wide range of variables related to team effectiveness according to the literature, and to 2) using structural equation modelling, assess the covariance between each of these variables as well as the correlation with other exogenous variables. Work role performance was measured with an adapted version of a work role questionnaire. Various independent variables including team manager characteristics, user characteristics, team profiles, clinical activities, organizational culture, network integration strategies and frequency/satisfaction of interactions with other teams or services were analyzed under the structural equation model. The later provided a good fit with the data. Frequent use of standardized procedures and evaluation tools (e.g. screening and assessment tools for mental health disorders) and team manager seniority exerted the most direct effect on work role performance. While network integration strategies had little effect on work role performance, there was a high covariance between this variable and those directly affecting work role performance among mental health teams. The results suggest that the mental healthcare system should apply standardized procedures and evaluation tools and, to a lesser extent, clinical approaches to improve work role performance in mental health teams. Overall, a more systematic implementation of network integration strategies may contribute to improved work role performance in mental health care. PMID:28991923

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

PubMed Central

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-01-01

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

Manipulating measurement scales in medical statistical analysis and data mining: A review of methodologies

PubMed Central

Marateb, Hamid Reza; Mansourian, Marjan; Adibi, Peyman; Farina, Dario

2014-01-01

Background: selecting the correct statistical test and data mining method depends highly on the measurement scale of data, type of variables, and purpose of the analysis. Different measurement scales are studied in details and statistical comparison, modeling, and data mining methods are studied based upon using several medical examples. We have presented two ordinal–variables clustering examples, as more challenging variable in analysis, using Wisconsin Breast Cancer Data (WBCD). Ordinal-to-Interval scale conversion example: a breast cancer database of nine 10-level ordinal variables for 683 patients was analyzed by two ordinal-scale clustering methods. The performance of the clustering methods was assessed by comparison with the gold standard groups of malignant and benign cases that had been identified by clinical tests. Results: the sensitivity and accuracy of the two clustering methods were 98% and 96%, respectively. Their specificity was comparable. Conclusion: by using appropriate clustering algorithm based on the measurement scale of the variables in the study, high performance is granted. Moreover, descriptive and inferential statistics in addition to modeling approach must be selected based on the scale of the variables. PMID:24672565

What makes patients with fibromyalgia feel better? Correlations between Patient Global Impression of Improvement and changes in clinical symptoms and function: a pooled analysis of 4 randomized placebo-controlled trials of duloxetine.

PubMed

Hudson, James I; Arnold, Lesley M; Bradley, Laurence A; Choy, Ernest H S; Mease, Philip J; Wang, Fujun; Ahl, Jonna; Wohlreich, Madelaine M

2009-11-01

To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I). Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings. Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r >or= 0.5 or r

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Do team processes really have an effect on clinical performance? A systematic literature review.

PubMed

Schmutz, J; Manser, T

2013-04-01

There is a growing literature on the relationship between team processes and clinical performance. The purpose of this review is to summarize these articles and examine the impact of team process behaviours on clinical performance. We conducted a literature search in five major databases. Inclusion criteria were: English peer-reviewed papers published between January 2001 and May 2012, which showed or tried to show (i) a statistical relationship of a team process variable and clinical performance or (ii) an improvement of a performance variable through a team process intervention. Study quality was assessed using predefined quality indicators. For every study, we calculated the relevant effect sizes. We included 28 studies in the review, seven of which were intervention studies. Every study reported at least one significant relationship between team processes or an intervention and performance. Also, some non-significant effects were reported. Most of the reported effect sizes were large or medium. The study quality ranged from medium to high. The studies are highly diverse regarding the specific team process behaviours investigated and also regarding the methods used. However, they suggest that team process behaviours do influence clinical performance and that training results in increased performance. Future research should rely on existing theoretical frameworks, valid, and reliable methods to assess processes such as teamwork or coordination and focus on the development of adequate tools to assess process performance, linking them with outcomes in the clinical setting.

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

PubMed Central

Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C.

2013-01-01

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results. PMID:23613961

A simple, rapid and validated high-performance liquid chromatography method suitable for clinical measurements of human mercaptalbumin and non-mercaptalbumin.

PubMed

Yasukawa, Keiko; Shimosawa, Tatsuo; Okubo, Shigeo; Yatomi, Yutaka

2018-01-01

Background Human mercaptalbumin and human non-mercaptalbumin have been reported as markers for various pathological conditions, such as kidney and liver diseases. These markers play important roles in redox regulations throughout the body. Despite the recognition of these markers in various pathophysiologic conditions, the measurements of human mercaptalbumin and non-mercaptalbumin have not been popular because of the technical complexity and long measurement time of conventional methods. Methods Based on previous reports, we explored the optimal analytical conditions for a high-performance liquid chromatography method using an anion-exchange column packed with a hydrophilic polyvinyl alcohol gel. The method was then validated using performance tests as well as measurements of various patients' serum samples. Results We successfully established a reliable high-performance liquid chromatography method with an analytical time of only 12 min per test. The repeatability (within-day variability) and reproducibility (day-to-day variability) were 0.30% and 0.27% (CV), respectively. A very good correlation was obtained with the results of the conventional method. Conclusions A practical method for the clinical measurement of human mercaptalbumin and non-mercaptalbumin was established. This high-performance liquid chromatography method is expected to be a powerful tool enabling the expansion of clinical usefulness and ensuring the elucidation of the roles of albumin in redox reactions throughout the human body.

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders.

PubMed

Clark, Sarah V; Mittal, Vijay A; Bernard, Jessica A; Ahmadi, Aral; King, Tricia Z; Turner, Jessica A

2018-03-01

Impaired clinical insight (CI) is a common symptom of psychotic disorders and a promising treatment target. However, to date, our understanding of how variability in CI is tied to underlying brain dysfunction in the clinical high-risk period is limited. Developing a stronger conception of this link will be a vital first step for efforts to determine if CI can serve as a useful prognostic indicator. The current study investigated whether variability in CI is related to major brain networks in adolescents and young adults at ultra high-risk (UHR) of developing psychosis. Thirty-five UHR youth were administered structured clinical interviews as well as an assessment for CI and underwent resting-state magnetic resonance imaging scans. Functional connectivity was calculated in the default mode network (DMN) and fronto-parietal network (FPN), two major networks that are dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN connectivity between the posterior cingulate/precuneus and ventromedial prefrontal cortex (DMN) was related to poorer CI (R 2 =0.399). There were no significant relationships between insight and the FPN. This is the first study to relate a major brain network to clinical insight before the onset of psychosis. Findings are consistent with evidence if a hyperconnected DMN in schizophrenia and UHR, and similar to a previous study of insight and connectivity in schizophrenia. Results suggest that a strongly connected DMN may be related to poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and young adults. Copyright © 2017 Elsevier B.V. All rights reserved.

On Becoming Trauma-Informed: Role of the Adverse Childhood Experiences Survey in Tertiary Child and Adolescent Mental Health Services and the Association with Standard Measures of Impairment and Severity.

PubMed

Rahman, Abdul; Perri, Andrea; Deegan, Avril; Kuntz, Jennifer; Cawthorpe, David

2018-01-01

There is a movement toward trauma-informed, trauma-focused psychiatric treatment. To examine Adverse Childhood Experiences (ACE) survey items by sex and by total scores by sex vs clinical measures of impairment to examine the clinical utility of the ACE survey as an index of trauma in a child and adolescent mental health care setting. Descriptive, polychoric factor analysis and regression analyses were employed to analyze cross-sectional ACE surveys (N = 2833) and registration-linked data using past admissions (N = 10,400) collected from November 2016 to March 2017 related to clinical data (28 independent variables), taking into account multicollinearity. Distinct ACE items emerged for males, females, and those with self-identified sex and for ACE total scores in regression analysis. In hierarchical regression analysis, the final models consisting of standard clinical measures and demographic and system variables (eg, repeated admissions) were associated with substantial ACE total score variance for females (44%) and males (38%). Inadequate sample size foreclosed on developing a reduced multivariable model for the self-identified sex group. The ACE scores relate to independent clinical measures and system and demographic variables. There are implications for clinical practice. For example, a child presenting with anxiety and a high ACE score likely requires treatment that is different from a child presenting with anxiety and an ACE score of zero. The ACE survey score is an important index of presenting clinical status that guides patient care planning and intervention in the progress toward a trauma-focused system of care.

Negative Mood and Obsessive-Compulsive Related Clinical Constructs: An Examination of Underlying Factors

PubMed Central

Britton, Gary I.; Davey, Graham C. L.

2017-01-01

Emerging evidence suggests that many of the clinical constructs used to help understand and explain obsessive-compulsive (OC) symptoms, and negative mood, may be causally interrelated. One approach to understanding this interrelatedness is a motivational systems approach. This approach suggests that rather than considering clinical constructs and negative affect as separable entities, they are all features of an integrated threat management system, and as such are highly coordinated and interdependent. The aim of the present study was to examine if clinical constructs related to OC symptoms and negative mood are best treated as separable or, alternatively, if these clinical constructs and negative mood are best seen as indicators of an underlying superordinate variable, as would be predicted by a motivational systems approach. A sample of 370 student participants completed measures of mood and the clinical constructs of inflated responsibility, intolerance of uncertainty, not just right experiences, and checking stop rules. An exploratory factor analysis suggested two plausible factor structures, one where all construct items and negative mood items loaded onto one underlying superordinate variable, and a second structure comprising of five factors, where each item loaded onto a factor representative of what the item was originally intended to measure. A confirmatory factor analysis showed that the five factor model was preferential to the one factor model, suggesting the four constructs and negative mood are best conceptualized as separate variables. Given the predictions of a motivational systems approach were not supported in the current study, other possible explanations for the causal interrelatedness between clinical constructs and negative mood are discussed. PMID:28959224

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

PubMed

Sokka, Tuulikki; Kautiainen, Hannu; Pincus, Theodore; Verstappen, Suzanne M M; Aggarwal, Amita; Alten, Rieke; Andersone, Daina; Badsha, Humeira; Baecklund, Eva; Belmonte, Miguel; Craig-Müller, Jürgen; da Mota, Licia Maria Henrique; Dimic, Alexander; Fathi, Nihal A; Ferraccioli, Gianfranco; Fukuda, Wataru; Géher, Pál; Gogus, Feride; Hajjaj-Hassouni, Najia; Hamoud, Hisham; Haugeberg, Glenn; Henrohn, Dan; Horslev-Petersen, Kim; Ionescu, Ruxandra; Karateew, Dmitry; Kuuse, Reet; Laurindo, Ieda Maria Magalhaes; Lazovskis, Juris; Luukkainen, Reijo; Mofti, Ayman; Murphy, Eithne; Nakajima, Ayako; Oyoo, Omondi; Pandya, Sapan C; Pohl, Christof; Predeteanu, Denisa; Rexhepi, Mjellma; Rexhepi, Sylejman; Sharma, Banwari; Shono, Eisuke; Sibilia, Jean; Sierakowski, Stanislaw; Skopouli, Fotini N; Stropuviene, Sigita; Toloza, Sergio; Valter, Ivo; Woolf, Anthony; Yamanaka, Hisashi

2010-01-01

Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

PubMed Central

2010-01-01

Introduction Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Conclusions Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA. PMID:20226018

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry.

PubMed

Krishnan, K; Lin, C-Y; Keswani, R; Pandolfino, J E; Kahrilas, P J; Komanduri, S

2014-08-01

Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra-esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification. EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. © 2014 John Wiley & Sons Ltd.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

PubMed Central

Krishnan, Kumar; Lin, Chen-Yuan; Keswani, Rajesh; Pandolfino, John E; Kahrilas, Peter J; Komanduri, Srinadh

2015-01-01

Background and aims Esophageal motor disorders are a heterogenous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. Methods We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification Key Results EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. Conclusions EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. PMID:25041229

Median regression spline modeling of longitudinal FEV1 measurements in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients.

PubMed

Conrad, Douglas J; Bailey, Barbara A; Hardie, Jon A; Bakke, Per S; Eagan, Tomas M L; Aarli, Bernt B

2017-01-01

Clinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations. Individual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts. Nine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms. Nonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

Low to high frequency ratio of heart rate variability spectra fails to describe sympatho-vagal balance in cardiac patients.

PubMed

Milicević, Goran

2005-06-01

Heart rate variability (HRV) reflects an influence of autonomic nervous system on heart work. In healthy subjects, ratio between low and high frequency components (LF/HF ratio) of HRV spectra represents a measure of sympatho-vagal balance. The ratio was defined by the authorities as an useful clinical tool, but it seems that it fails to summarise sympatho-vagal balance in a clinical setting. Value of the method was re-evaluated in several categories of cardiac patients. HRV was analysed from 24-hour Holter ECGs in 132 healthy subjects, and 2159 cardiac patients dichotomised by gender, median of age, diagnosis of myocardial infarction or coronary artery surgery, left ventricular systolic function and divided by overall HRV into several categories. In healthy subjects, LF/HF ratio correlated with overall HRV negatively, as expected. The paradoxical finding was obtained in cardiac patients; the lower the overall HRV and the time-domain indices of vagal modulation activity were the lower the LF/HF ratio was. If used as a measure of sympatho-vagal balance, long-term recordings of LF/HF ratio contradict to clinical finding and time-domain HRV indices in cardiac patients. The ratio cannot therefore be used as a reliable marker of autonomic activity in a clinical setting.

Genetics of platelet inhibitor treatment

PubMed Central

Trenk, Dietmar; Hochholzer, Willibald

2014-01-01

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the standard of care in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) because this regimen has markedly decreased the rate of cardiovascular events. The substantial variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. Baseline demographic and clinical variables contributing to the observed variability have been identified. Besides this, research within the past decade has focused on the impact of genetic polymorphisms encoding transport systems or enzymes involved in the absorption and metabolism of these drugs. Loss-of-function polymorphisms in CYP2C19 are the strongest individual variables affecting pharmacokinetics and antiplatelet response to clopidogrel, but explain no more than 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. No genetic variables contributing to clinical outcomes of patients treated with the newer P2Y12 receptor antagonists, prasugrel or ticagrelor, have been identified so far. This review aims to provide an update on the current status of genotype-based personalized therapy with clopidogrel. PMID:23981082

Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival

PubMed Central

Visco, Carlo; Falisi, Erika; Young, Ken H.; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

2015-01-01

The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P < .0001). No relation was found between high EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL. PMID:26087198

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

PubMed

Dakwar, Elias; Nunes, Edward V; Bisaga, Adam; Carpenter, Kenneth C; Mariani, John P; Sullivan, Maria A; Raby, Wilfrid N; Levin, Frances R

2011-01-01

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process. © American Academy of Addiction Psychiatry.

[Waardenburg syndrome. A heterogenic disorder with variable penetrance].

PubMed

Apaydin, F; Bereketoglu, M; Turan, O; Hribar, K; Maassen, M M; Günhan, O; Zenner, H-P; Pfister, M

2004-06-01

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

When to trust our learners? Clinical teachers' perceptions of decision variables in the entrustment process.

PubMed

Duijn, Chantal C M A; Welink, Lisanne S; Bok, Harold G J; Ten Cate, Olle T J

2018-06-01

Clinical training programs increasingly use entrustable professional activities (EPAs) as focus of assessment. However, questions remain about which information should ground decisions to trust learners. This qualitative study aimed to identify decision variables in the workplace that clinical teachers find relevant in the elaboration of the entrustment decision processes. The findings can substantiate entrustment decision-making in the clinical workplace. Focus groups were conducted with medical and veterinary clinical teachers, using the structured consensus method of the Nominal Group Technique to generate decision variables. A ranking was made based on a relevance score assigned by the clinical teachers to the different decision variables. Field notes, audio recordings and flip chart lists were analyzed and subsequently translated and, as a form of axial coding, merged into one list, combining the decision variables that were similar in their meaning. A list of 11 and 17 decision variables were acknowledged as relevant by the medical and veterinary teacher groups, respectively. The focus groups yielded 21 unique decision variables that were considered relevant to inform readiness to perform a clinical task on a designated level of supervision. The decision variables consisted of skills, generic qualities, characteristics, previous performance or other information. We were able to group the decision variables into five categories: ability, humility, integrity, reliability and adequate exposure. To entrust a learner to perform a task at a specific level of supervision, a supervisor needs information to support such a judgement. This trust cannot be credited on a single case at a single moment of assessment, but requires different variables and multiple sources of information. This study provides an overview of decision variables giving evidence to justify the multifactorial process of making an entrustment decision.

Glycaemic variability in patients with severe sepsis or septic shock admitted to an Intensive Care Unit.

PubMed

Silveira, L M; Basile-Filho, A; Nicolini, E A; Dessotte, C A M; Aguiar, G C S; Stabile, A M

2017-08-01

Sepsis is associated with morbidity and mortality, which implies high costs to the global health system. Metabolic alterations that increase glycaemia and glycaemic variability occur during sepsis. To verify mean body glucose levels and glycaemic variability in Intensive Care Unit (ICU) patients with severe sepsis or septic shock. Retrospective and exploratory study that involved collection of patients' sociodemographic and clinical data and calculation of severity scores. Glycaemia measurements helped to determine glycaemic variability through standard deviation and mean amplitude of glycaemic excursions. Analysis of 116 medical charts and 6730 glycaemia measurements revealed that the majority of patients were male and aged over 60 years. Surgical treatment was the main reason for ICU admission. High blood pressure and diabetes mellitus were the most usual comorbidities. Patients that died during the ICU stay presented the highest SOFA scores and mean glycaemia; they also experienced more hypoglycaemia events. Patients with diabetes had higher mean glycaemia, evaluated through standard deviation and mean amplitude of glycaemia excursions. Organic impairment at ICU admission may underlie glycaemic variability and lead to a less favourable outcome. High glycaemic variability in patients with diabetes indicates that monitoring of these individuals is crucial to ensure better outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Visit-to-visit blood pressure variability: clinical and prognostic significance].

PubMed

Kotovskaia, Iu V; Troitskaia, E A; Kobalava, Zh D

2014-01-01

The phenomenon of variability of blood pressure (BP) was studied for a long time, but recently it has received increased attention, with the focus shifted from short-term BP variability, estimated at daily monitoring for clinical blood pressure variability from visit to visit, which can be regarded as one of the indicators quality control of blood pressure with prolonged treatment. In light of the recent years of clinical data from visit to visit BP variability seems a promising new target for antihypertensive therapy.

Implementation and utilization of genetic testing in personalized medicine

PubMed Central

Abul-Husn, Noura S; Owusu Obeng, Aniwaa; Sanderson, Saskia C; Gottesman, Omri; Scott, Stuart A

2014-01-01

Clinical genetic testing began over 30 years ago with the availability of mutation detection for sickle cell disease diagnosis. Since then, the field has dramatically transformed to include gene sequencing, high-throughput targeted genotyping, prenatal mutation detection, preimplantation genetic diagnosis, population-based carrier screening, and now genome-wide analyses using microarrays and next-generation sequencing. Despite these significant advances in molecular technologies and testing capabilities, clinical genetics laboratories historically have been centered on mutation detection for Mendelian disorders. However, the ongoing identification of deoxyribonucleic acid (DNA) sequence variants associated with common diseases prompted the availability of testing for personal disease risk estimation, and created commercial opportunities for direct-to-consumer genetic testing companies that assay these variants. This germline genetic risk, in conjunction with other clinical, family, and demographic variables, are the key components of the personalized medicine paradigm, which aims to apply personal genomic and other relevant data into a patient’s clinical assessment to more precisely guide medical management. However, genetic testing for disease risk estimation is an ongoing topic of debate, largely due to inconsistencies in the results, concerns over clinical validity and utility, and the variable mode of delivery when returning genetic results to patients in the absence of traditional counseling. A related class of genetic testing with analogous issues of clinical utility and acceptance is pharmacogenetic testing, which interrogates sequence variants implicated in interindividual drug response variability. Although clinical pharmacogenetic testing has not previously been widely adopted, advances in rapid turnaround time genetic testing technology and the recent implementation of preemptive genotyping programs at selected medical centers suggest that personalized medicine through pharmacogenetics is now a reality. This review aims to summarize the current state of implementing genetic testing for personalized medicine, with an emphasis on clinical pharmacogenetic testing. PMID:25206309

P09.62 Towards individualized survival prediction in glioblastoma patients using machine learning methods

PubMed Central

Vera, L.; Pérez-Beteta, J.; Molina, D.; Borrás, J. M.; Benavides, M.; Barcia, J. A.; Velásquez, C.; Albillo, D.; Lara, P.; Pérez-García, V. M.

2017-01-01

Abstract Introduction: Machine learning methods are integrated in clinical research studies due to their strong capability to discover parameters having a high information content and their predictive combined potential. Several studies have been developed using glioblastoma patient’s imaging data. Many of them have focused on including large numbers of variables, mostly two-dimensional textural features and/or genomic data, regardless of their meaning or potential clinical relevance. Materials and methods: 193 glioblastoma patients were included in the study. Preoperative 3D magnetic resonance images were collected and semi-automatically segmented using an in-house software. After segmentation, a database of 90 parameters including geometrical and textural image-based measures together with patients’ clinical data (including age, survival, type of treatment, etc.) was constructed. The criterion for including variables in the study was that they had either shown individual impact on survival in single or multivariate analyses or have a precise clinical or geometrical meaning. These variables were used to perform several machine learning experiments. In a first set of computational cross-validation experiments based on regression trees, those attributes showing the highest information measures were extracted. In the second phase, more sophisticated learning methods were employed in order to validate the potential of the previous variables predicting survival. Concretely support vector machines, neural networks and sparse grid methods were used. Results: Variables showing high information measure in the first phase provided the best prediction results in the second phase. Specifically, patient age, Stupp regimen and a geometrical measure related with the irregularity of contrast-enhancing areas were the variables showing the highest information measure in the first stage. For the second phase, the combinations of patient age and Stupp regimen together with one tumor geometrical measure and one tumor heterogeneity feature reached the best quality prediction. Conclusions: Advanced machine learning methods identified the parameters with the highest information measure and survival predictive potential. The uninformed machine learning methods identified a novel feature measure with direct impact on survival. Used in combination with other previously known variables multi-indexes can be defined that can help in tumor characterization and prognosis prediction. Recent advances on the definition of those multi-indexes will be reported in the conference. Funding: James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Collaborative award 220020450 and planning grant 220020420], MINECO/FEDER [MTM2015-71200-R], JCCM [PEII-2014-031-P].

Clinical and Pharmacogenetic Predictors of Circulating Atorvastatin and Rosuvastatin Concentration in Routine Clinical Care

PubMed Central

DeGorter, Marianne K.; Tirona, Rommel G.; Schwarz, Ute I.; Choi, Yun-Hee; Dresser, George K.; Suskin, Neville; Myers, Kathryn; Zou, GuangYong; Iwuchukwu, Otito; Wei, Wei-Qi; Wilke, Russell A.; Hegele, Robert A.; Kim, Richard B.

2014-01-01

Background A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients. Methods and Results In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient referral center. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression. We observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for gender, age, body mass index, ethnicity, dose, and time from last dose, SLCO1B1 c.521T>C (p < 0.001) and ABCG2 c.421C>A (p < 0.01) were important to rosuvastatin concentration (adjusted R2 = 0.56 for the final model). Atorvastatin concentration was associated with SLCO1B1 c.388A>G (p < 0.01) and c.521T>C (p < 0.05), and 4β-hydroxycholesterol, a CYP3A activity marker (adjusted R2 = 0.47). A second cohort of 579 patients from primary and specialty care databases were retrospectively genotyped. In this cohort, genotypes associated with statin concentration were not differently distributed among dosing groups, implying providers had not yet optimized each patient's risk-benefit ratio. Nearly 50% of patients in routine practice taking the highest doses were predicted to have statin concentrations greater than the 90th percentile. Conclusions Interindividual variability in statin exposure in patients is associated with uptake and efflux transporter polymorphisms. An algorithm incorporating genomic and clinical variables to avoid high atorvastatin and rosuvastatin levels is described; further study will determine if this approach reduces incidence of statin-myopathy. PMID:23876492

Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains

PubMed Central

Centurion-Lara, Arturo; Giacani, Lorenzo; Godornes, Charmie; Molini, Barbara J.; Brinck Reid, Tara; Lukehart, Sheila A.

2013-01-01

Background The pathogenic non-cultivable treponemes include three subspecies of Treponema pallidum (pallidum, pertenue, endemicum), T. carateum, T. paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme (Simian isolate). These treponemes are morphologically indistinguishable and antigenically and genetically highly similar, yet cross-immunity is variable or non-existent. Although all of these organisms cause chronic, multistage skin and systemic disease, they have historically been classified by mode of transmission, clinical presentations and host ranges. Whole genome studies underscore the high degree of sequence identity among species, subspecies and strains, pinpointing a limited number of genomic regions for variation. Many of these “hot spots” include members of the tpr gene family, composed of 12 paralogs encoding candidate virulence factors. We hypothesize that the distinct clinical presentations, host specificity, and variable cross-immunity might reside on virulence factors such as the tpr genes. Methodology/Principal Findings Sequence analysis of 11 tpr loci (excluding tprK) from 12 strains demonstrated an impressive heterogeneity, including SNPs, indels, chimeric genes, truncated gene products and large deletions. Comparative analyses of sequences and 3D models of predicted proteins in Subfamily I highlight the striking co-localization of discrete variable regions with predicted surface-exposed loops. A hallmark of Subfamily II is the presence of chimeric genes in the tprG and J loci. Diversity in Subfamily III is limited to tprA and tprL. Conclusions/Significance An impressive sequence variability was found in tpr sequences among the Treponema isolates examined in this study, with most of the variation being consistent within subspecies or species, or between syphilis vs. non-syphilis strains. Variability was seen in the pallidum subspecies, which can be divided into 5 genogroups. These findings support a genetic basis for the classification of these organisms into their respective subspecies and species. Future functional studies will determine whether the identified genetic differences relate to cross-immunity, clinical differences, or host ranges. PMID:23696912

N-terminal pro-brain natriuretic peptide and associated factors in the general working population: a baseline survey of the Uranosaki cohort study.

PubMed

Tanaka, Atsushi; Yoshida, Hisako; Kawaguchi, Atsushi; Oyama, Jun-Ichi; Kotooka, Norihiko; Toyoda, Shigeru; Inoue, Teruo; Natsuaki, Masafumi; Node, Koichi

2017-07-19

Few data on clinical characteristics associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) or the clinical value of measuring NT-proBNP in the working population are available. The aim of the present study was to investigate the levels of NT-proBNP and their association with clinical variables in the Japanese general working population by using baseline data from the Uranosaki cohort study. In the study, the plasma concentration of NT-proBNP and some biomarkers were measured in addition to the standard health checkups at the workplace. Questionnaires regarding health-related quality of life (HR-QOL) were also completed. A total of 2140 participants were enrolled in the study. Plasma levels of NT-proBNP were positively associated with age, female sex, systolic blood pressure, pulse pressure, prevalent hypertension, smoking habit, high-density lipoprotein cholesterol (HDL-C), and prevalent proteinuria, and negatively associated with body mass index, lipid profiles except HDL-C, uric acid, renal function, and hemoglobin. Both the plasma concentration of high-molecular weight adiponectin and that of high-sensitivity troponin T were positively and independently associated with NT-proBNP. In addition, the HR-QOL score regarding sleep disorder was independently associated with NT-proBNP. Thus, we have obtained evidence that the plasma NT-proBNP is affected by several clinical variables in the general working population.

Heart rate variability in patients with systemic lupus erythematosus: a systematic review and methodological considerations.

PubMed

Matusik, P S; Matusik, P T; Stein, P K

2018-07-01

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.

Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

PubMed

Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

2018-05-01

The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(＜4, ≥4 and, ＜8, ≥8 and, ＜12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p ＜0.05). The categorical variables of VDE (＜4 mm/y, ≥4 mm/y and, ＜8 mm/y, ≥8 mm/y and, ＜12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

One year in review 2016: systemic lupus erythematosus.

PubMed

Adinolfi, Antonella; Valentini, Eleonora; Calabresi, Emanuele; Tesei, Giulia; Signorini, Viola; Barsotti, Simone; Tani, Chiara

2016-01-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly variable course and prognosis. The management of the disease is still a clinical challenge for the treating physicians as many aspects regarding the disease pathogenesis, clinical picture and outcomes remain to be elucidated. New and interesting data are emerging; here the recent literature on SLE pathogenesis, clinical and laboratory aspects, as well as treatments and comorbidities, are reviewed and the main findings summarised in order to provide a bird's eye on the relevant papers on these topics.

Clinical dysphagia risk predictors after prolonged orotracheal intubation

PubMed Central

de Medeiros, Gisele Chagas; Sassi, Fernanda Chiarion; Mangilli, Laura Davison; Zilberstein, Bruno; de Andrade, Claudia Regina Furquim

2014-01-01

OBJECTIVES: To elucidate independent risk factors for dysphagia after prolonged orotracheal intubation. METHODS: The participants were 148 consecutive patients who underwent clinical bedside swallowing assessments from September 2009 to September 2011. All patients had received prolonged orotracheal intubations and were admitted to one of several intensive care units of a large Brazilian school hospital. The correlations between the conducted water swallow test results and dysphagia risk levels were analyzed for statistical significance. RESULTS: Of the 148 patients included in the study, 91 were male and 57 were female (mean age, 53.64 years). The univariate analysis results indicated that specific variables, including extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking, and other signs, were possible significant high-risk indicators of dysphagia onset. The multivariate analysis results indicated that cervical auscultation and coughing were independent predictive variables for high dysphagia risk. CONCLUSIONS: Patients displaying extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking and other signs should benefit from early swallowing evaluations. Additionally, early post-extubation dysfunction recognition is paramount in reducing the morbidity rate in this high-risk population. PMID:24473554

Evaluation of a highly discriminating multiplex multi-locus variable-number of tandem-repeats (MLVA) analysis for Vibrio cholerae.

PubMed

Olsen, Jaran S; Aarskaug, Tone; Skogan, Gunnar; Fykse, Else Marie; Ellingsen, Anette Bauer; Blatny, Janet M

2009-09-01

Vibrio cholerae is the etiological agent of cholera and may be used in bioterror actions due to the easiness of its dissemination, and the public fear for acquiring the cholera disease. A simple and highly discriminating method for connecting clinical and environmental isolates of V. cholerae is needed in microbial forensics. Twelve different loci containing variable numbers of tandem-repeats (VNTRs) were evaluated in which six loci were polymorphic. Two multiplex reactions containing PCR primers targeting these six VNTRs resulted in successful DNA amplification of 142 various environmental and clinical V. cholerae isolates. The genetic distribution inside the V. cholerae strain collection was used to evaluate the discriminating power (Simpsons Diversity Index=0.99) of this new MLVA analysis, showing that the assay have a potential to differentiate between various strains, but also to identify those isolates which are collected from a common V. cholerae outbreak. This work has established a rapid and highly discriminating MLVA assay useful for track back analyses and/or forensic studies of V. cholerae infections.

[Acute aortic dissection. Differential diagnosis of a thoracic emergency].

PubMed

Grundmann, U; Lausberg, H; Schäfers, H-J

2006-01-01

Acute aortic dissection is an infrequent but important differential diagnosis of acute chest pain. The variability of presenting symptoms makes it difficult to diagnose correctly. Important clinical indicators - besides chest pain - are symptoms related to acute aortic insufficiency and/or pericardial tamponade, variable acute neurologic alterations, or signs of peripheral or visceral malperfusion. The spontaneous prognosis depends on the location and extent of the dissection, and left untreated dissection carries a high mortality. The key goal of preclinical treatment is stabilization with analgesia, mild sedation (opioids, benzodiazepines) and treatment of hypertension (beta-blockers) or hypotension (fluid administration). If the patient presents with a high probability of dissection, early transfer to a specialized center appears advisable. Initial clinical diagnostic studies include transthoracic echocardiogram and computed tomography. If the ascending aorta is involved (Stanford type A) immediate replacement of the proximal aorta is necessary. Isolated dissections of the descending aorta (type B) require aggressive blood pressure control, but can be managed conservatively in most cases. A high level of vigilance is necessary in all patients to detect and treat visceral ischemia.

Clinical dysphagia risk predictors after prolonged orotracheal intubation.

PubMed

Medeiros, Gisele Chagas de; Sassi, Fernanda Chiarion; Mangilli, Laura Davison; Zilberstein, Bruno; Andrade, Claudia Regina Furquim de

2014-01-01

To elucidate independent risk factors for dysphagia after prolonged orotracheal intubation. The participants were 148 consecutive patients who underwent clinical bedside swallowing assessments from September 2009 to September 2011. All patients had received prolonged orotracheal intubations and were admitted to one of several intensive care units of a large Brazilian school hospital. The correlations between the conducted water swallow test results and dysphagia risk levels were analyzed for statistical significance. Of the 148 patients included in the study, 91 were male and 57 were female (mean age, 53.64 years). The univariate analysis results indicated that specific variables, including extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking, and other signs, were possible significant high-risk indicators of dysphagia onset. The multivariate analysis results indicated that cervical auscultation and coughing were independent predictive variables for high dysphagia risk. Patients displaying extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking and other signs should benefit from early swallowing evaluations. Additionally, early post-extubation dysfunction recognition is paramount in reducing the morbidity rate in this high-risk population.

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

PubMed

Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

2017-04-01

To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Growth hormone responsiveness: peak stimulated growth hormone levels and other variables in idiopathic short stature (ISS): data from the National Cooperative Growth Study.

PubMed

Moore, Wayne V; Dana, Ken; Frane, James; Lippe, Barbara

2008-09-01

In children with idiopathic short stature (ISS), growth hormone (GH) response to a provocative test will be inversely related to the first year response to hGH and be a variable accounting for a degree of responsiveness. Because high levels of GH are a characteristic of GH insensitivity, such as in Laron syndrome, it is possible that a high stimulated GH is associated with a lower first year height velocity among children diagnosed as having ISS. We examined the relationship between the peak stimulated GH levels in 3 ISS groups; GH >10 -<25, 25-40, and >40 ng/mL and the first year growth response to rhGH therapy. We also looked at 8 other predictor variables (age, sex, height SDS, height age, body mass index (BMI), bone age, dose, and SDS deficit from target parental height. Multiple regression analysis with the first year height as the dependent variable and peak stimulated GH was the primary endpoint. The predictive value of adding each of the other variables was then assessed. Mean change in height velocity was similar among the three groups, with a maximum difference among the groups of 0.6 cm/yr. There was a small but statistically significant correlation (r=-0.12) between the stimulated GH and first year height velocity. The small correlation between first year growth response and peak GH is not clinically relevant in defining GH resistance. No cut off level by peak GH could be determined to enhance the usefulness of this measure to predict response. Baseline age was the only clinically significant predictor, R-squared, 6.4%. All other variables contributed less than an additional 2% to the R-squared.

Prediction of remission of depression with clinical variables, neuropsychological performance, and serotonergic/dopaminergic gene polymorphisms.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Asbun-Bojalil, Juan; Lira-Islas, Yuridia; Reyes-Ponce, Celia; Guàrdia-Olmos, Joan

2012-11-01

The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

[Prevalence and factors associated with burnout in a health area].

PubMed

Caballero Martín, M; Bermejo Fernández, F; Nieto Gómez, R; Caballero Martínez, F

2001-03-31

The main objective was to determine the prevalence of the burnout syndrome among health workers and its distribution by social, demographic and work variables. The secondary aim was to detect potentially modifiable causes. Descriptive cross-sectional study. Primary care. All the 354 doctors, nurses and clinical auxiliaries belonging to the 22 primary care teams of Area VI, Madrid. A self-administered, anonymous questionnaire was sent out by internal mail. This had three instruments: a questionnaire on social and demographic variables, the validated questionnaire known as the Maslach Burnout Inventory and an open opinion section. High levels of burnout were detected: 30.6% in the high range on the emotional tiredness sub-scale, with higher scores among men (p = 0.026). There were also more paediatric staff affected in personal achievements. There was scant relationship of the syndrome to social variables. 43.9% thought they suffered or had suffered from some kind of physical or psychological disorder directly related to exercising their profession. 38.3% associated directly their burnout with the excess demand habitually experienced in clinics. We detected worryingly high levels of this syndrome among our professionals, similar to other surveys in Spain. The subjects of the survey linked their unease with certain work factors that could easily be modified. The training received in techniques of self-control and stress management is clearly insufficient.

Microscope-aided endodontic treatment of maxillary first premolars with three roots: a case series.

PubMed

Karumaran, C S; Gunaseelan, R; Krithikadatta, J

2011-01-01

Maxillary premolars have a highly variable root canal morphology. However, the presence of three roots is a rare occurrence. This clinical article describes the unusual anatomy detected in maxillary premolars during routine endodontic treatment using microscope. The diagnosis and clinical management of maxillary first premolars with three roots and canals using radiographic interpretation, access cavity modification and visual enhancement with operative microscopes is discussed in the article.

Quality requirements for veterinary hematology analyzers in small animals-a survey about veterinary experts' requirements and objective evaluation of analyzer performance based on a meta-analysis of method validation studies: bench top hematology analyzer.

PubMed

Cook, Andrea M; Moritz, Andreas; Freeman, Kathleen P; Bauer, Natali

2016-09-01

Scarce information exists about quality requirements and objective evaluation of performance of large veterinary bench top hematology analyzers. The study was aimed at comparing the observed total error (TEobs ) derived from meta-analysis of published method validation data to the total allowable error (TEa ) for veterinary hematology variables in small animals based on experts' opinions. Ideally, TEobs should be < TEa . An online survey was sent to veterinary experts in clinical pathology and small animal internal medicine for providing the maximal allowable deviation from a given result for each variable. Percent of TEa = (allowable median deviation/clinical threshold) * 100%. Second, TEobs for 3 laser-based bench top hematology analyzers (ADVIA 2120; Sysmex XT2000iV, and CellDyn 3500) was calculated based on method validation studies published between 2005 and 2013 (n = 4). The percent TEobs = 2 * CV (%) + bias (%). The CV was derived from published studies except for the ADVIA 2120 (internal data), and bias was estimated from the regression equation. A total of 41 veterinary experts (19 diplomates, 8 residents, 10 postgraduate students, 4 anonymous specialists) responded. The proposed range of TEa was wide, but generally ≤ 20%. The TEobs was < TEa for all variables and analyzers except for canine and feline HGB (high bias, low CV) and platelet counts (high bias, high CV). Overall, veterinary bench top analyzers fulfilled experts' requirements except for HGB due to method-related bias, and platelet counts due to known preanalytic/analytic issues. © 2016 American Society for Veterinary Clinical Pathology.

High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

PubMed

van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

2017-12-01

Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

Clinical and Microbiological Features of HIV-Associated Tuberculous Meningitis in Vietnamese Adults

PubMed Central

Torok, M. Estee; Chau, Tran Thi Hong; Mai, Pham Phuong; Phong, Nguyen Duy; Dung, Nguyen Thi; Chuong, Ly Van; Lee, Sue J.; Caws, M.; de Jong, Menno D.; Hien, Tran Tinh; Farrar, Jeremy J.

2008-01-01

Methods The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death. Results The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm3. CSF findings were as follows: median leucocyte count 438×109cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003). Conclusions HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage. PMID:18350135

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study

PubMed Central

Timmer, Margriet R.; Martinez, Pierre; Lau, Chiu T.; Westra, Wytske M.; Calpe, Silvia; Rygiel, Agnieszka M.; Rosmolen, Wilda D.; Meijer, Sybren L.; ten Kate, Fiebo J.W.; Dijkgraaf, Marcel G.W.; Mallant-Hent, Rosalie C.; Naber, Anton H.J.; van Oijen, Arnoud H.A.M.; Baak, Lubbertus C.; Scholten, Pieter; Böhmer, Clarisse J.M.; Fockens, Paul; Maley, Carlo C.; Graham, Trevor A.; Bergman, Jacques J.G.H.M.; Krishnadath, Kausilia K.

2016-01-01

Objective The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. Methods In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC, and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver-operating-characteristic curves and a leave-one-out analysis. Results A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain, and aneusomy, were significantly associated with progression on univariate analysis. We defined an ‘Abnormal Marker Count’ that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI, 2.6 to 29.8) increased hazard ratio compared with the low-risk group, with an area under the curve of 0.76 (95% CI, 0.66 to 0.86). Conclusion A prediction model based on age, Barrett's length, and the markers p16, MYC, and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. PMID:26104750

Laboratory-Based Biomarkers and Liver Metastases in Metastatic Castration-Resistant Prostate Cancer.

PubMed

Cotogno, Patrick M; Ranasinghe, Lahiru K; Ledet, Elisa M; Lewis, Brian E; Sartor, Oliver

2018-04-26

Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate-specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized. Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases ( p  < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome. Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting. The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate-resistant prostate cancer. The results indicate that quantitative assessments of aspartate transaminase, lactate dehydrogenase, and hemoglobin are significantly associated with an increased probability of having documented radiographic liver metastases. Analysis of these simple variables can alert clinicians to those at high risk for prostate cancer that has spread to the liver, a finding of clear importance for clinical management. © AlphaMed Press 2018.

Variability of indication criteria in knee and hip replacement: an observational study

PubMed Central

2010-01-01

Background Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication. Methods The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated. The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity. Results The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate. Conclusions A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates. PMID:20977745

Variability of indication criteria in knee and hip replacement: an observational study.

PubMed

Cobos, Raquel; Latorre, Amaia; Aizpuru, Felipe; Guenaga, Jose I; Sarasqueta, Cristina; Escobar, Antonio; García, Lidia; Herrera-Espiñeira, Carmen

2010-10-26

Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication. The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated.The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity. The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate. A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates.

Predicting high-risk preterm birth using artificial neural networks.

PubMed

Catley, Christina; Frize, Monique; Walker, C Robin; Petriu, Dorina C

2006-07-01

A reengineered approach to the early prediction of preterm birth is presented as a complimentary technique to the current procedure of using costly and invasive clinical testing on high-risk maternal populations. Artificial neural networks (ANNs) are employed as a screening tool for preterm birth on a heterogeneous maternal population; risk estimations use obstetrical variables available to physicians before 23 weeks gestation. The objective was to assess if ANNs have a potential use in obstetrical outcome estimations in low-risk maternal populations. The back-propagation feedforward ANN was trained and tested on cases with eight input variables describing the patient's obstetrical history; the output variables were: 1) preterm birth; 2) high-risk preterm birth; and 3) a refined high-risk preterm birth outcome excluding all cases where resuscitation was delivered in the form of free flow oxygen. Artificial training sets were created to increase the distribution of the underrepresented class to 20%. Training on the refined high-risk preterm birth model increased the network's sensitivity to 54.8%, compared to just over 20% for the nonartificially distributed preterm birth model.

Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics.

PubMed

Medem, Anna V; Seidling, Hanna M; Eichler, Hans-Georg; Kaltschmidt, Jens; Metzner, Michael; Hubert, Carina M; Czock, David; Haefeli, Walter E

2017-05-01

Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics. An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs. The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster "drug characterization" specifies the nature of the drug. The cluster "dosage" provides information on approved drug dosages and defines corresponding specific conditions. The cluster "clinical pharmacokinetics" includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables. By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

The importance of extreme weight percentile in postoperative morbidity in children.

PubMed

Stey, Anne M; Moss, R Lawrence; Kraemer, Kari; Cohen, Mark E; Ko, Clifford Y; Lee Hall, Bruce

2014-05-01

Anthropometric data are important indicators of child health. This study sought to determine whether anthropometric data of extreme weight were significant predictors of perioperative morbidity in pediatric surgery. This was a cohort study of children 29 days up to 18 years of age undergoing surgical procedures at participating American College of Surgeons' NSQIP Pediatric hospitals in 2011 and 2012. The primary outcomes were composite morbidity and surgical site infection. The primary predictor of interest was weight percentile, which was divided into the following categories: ≤5(th) percentile, 6(th) to 94(th), or ≥95(th) percentile. A hierarchical multivariate logistic model, adjusting for procedure case mix, demographic, and clinical patient characteristic variables, was used to quantify the relationship between weight percentile category and outcomes. Children in the ≤5th weight percentile had 1.19-fold higher odds of overall postoperative morbidity developing than children in the nonextreme range (95% CI, 1.10-1.30) when controlling for clinical variables. Yet these children did not have higher odds of surgical site infection developing. Children in the ≥95(th) weight percentile did not have a significant increase in overall postoperative morbidity. However, they were at 1.35-fold increased odds of surgical site infection compared with those in the nonextreme range when controlling for clinical variables (95% CI, 1.16-1.57). Both extremely high and extremely low weight percentile scores can be associated with increased postoperative complications after controlling for clinical variables. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Kinematic measures of Arm-trunk movements during unilateral and bilateral reaching predict clinically important change in perceived arm use in daily activities after intensive stroke rehabilitation.

PubMed

Chen, Hao-ling; Lin, Keh-chung; Liing, Rong-jiuan; Wu, Ching-yi; Chen, Chia-ling

2015-09-21

Kinematic analysis has been used to objectively evaluate movement patterns, quality, and strategies during reaching tasks. However, no study has investigated whether kinematic variables during unilateral and bilateral reaching tasks predict a patient's perceived arm use during activities of daily living (ADL) after an intensive intervention. Therefore, this study investigated whether kinematic measures during unilateral and bilateral reaching tasks before an intervention can predict clinically meaningful improvement in perceived arm use during ADL after intensive poststroke rehabilitation. The study was a secondary analysis of 120 subjects with chronic stroke who received 90-120 min of intensive intervention every weekday for 3-4 weeks. Reaching kinematics during unilateral and bilateral tasks and the Motor Activity Log (MAL) were evaluated before and after the intervention. Kinematic variables explained 22 and 11 % of the variance in actual amount of use (AOU) and quality of movement (QOM), respectively, of MAL improvement during unilateral reaching tasks. Kinematic variables also explained 21 and 31 % of the variance in MAL-AOU and MAL-QOM, respectively, during bilateral reaching tasks. Selected kinematic variables, including endpoint variables, trunk involvement, and joint recruitment and interjoint coordination, were significant predictors for improvement in perceived arm use during ADL (P < 0.05). Arm-trunk kinematics may be used to predict clinically meaningful improvement in perceived arm use during ADL after intensive rehabilitation. Involvement of interjoint coordination and trunk control variables as predictors in bilateral reaching models indicates that a high level of motor control (i.e., multijoint coordination) and trunk stability may be important in obtaining treatment gains in arm use, especially for bilateral daily activities, in intensive rehabilitation after stroke.

Behavioral Marital Bibliotherapy: An Initial Investigation of Therapeutic Efficacy.

ERIC Educational Resources Information Center

Bornstein, Philip H.; And Others

1984-01-01

Reports an attempt to validate a self-help behavioral marital bibliotherapy program. Evaluated five clinical distressed couples via a multiple baseline analysis. Treatment involved reading and exercises covering communications, problem solving, and sexual dysfunction. Results were highly variable and reflected minimal change. (BH)

SU-E-I-88: Realistic Pathological Simulations of the NCAT and Zubal Anthropomorphic Models, Based on Clinical PET/CT Data.

PubMed

Papadimitroulas, P; Loudos, G; Le Maitre, A; Efthimiou, N; Visvikis, D; Nikiforidis, G; Kagadis, G C

2012-06-01

In the present study a patient-specific dataset of realistic PET simulations was created, taking into account the variability of clinical oncology data. Tumor variability was tested in the simulated results. A comparison of the produced simulated data was performed to clinical PET/CT data, for the validation and the evaluation of the procedure. Clinical PET/CT data of oncology patients were used as the basis of the simulated variability inserting patient-specific characteristics in the NCAT and the Zubal anthropomorphic phantoms. GATE Monte Carlo toolkit was used for simulating a commercial PET scanner. The standard computational anthropomorphic phantoms were adapted to the CT data (organ shapes), using a fitting algorithm. The activity map was derived from PET images. Patient tumors were segmented and inserted in the phantom, using different activity distributions. The produced simulated data were reconstructed using the STIR opensource software and compared to the original clinical ones. The accuracy of the procedure was tested in four different oncology cases. Each pathological situation was illustrated simulating a) a healthy body, b) insertion of the clinical tumor with homogenous activity, and c) insertion of the clinical tumor with variable activity (voxel-by-voxel) based on the clinical PET data. The accuracy of the presented dataset was compared to the original PET/CT data. Partial Volume Correction (PVC) was also applied in the simulated data. In this study patient-specific characteristics were used in computational anthropomorphic models for simulating realistic pathological patients. Voxel-by-voxel activity distribution with PVC within the tumor gives the most accurate results. Radiotherapy applications can utilize the benefits of the accurate realistic imaging simulations, using the anatomicaland biological information of each patient. Further work will incorporate the development of analytical anthropomorphic models with motion and cardiac correction, combined with pathological patients to achieve high accuracy in tumor imaging. This research was supported by the Joint Research and Technology Program between Greece and France; 2009-2011 (protocol ID: 09FR103). © 2012 American Association of Physicists in Medicine.

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

PubMed

Yang, Lun; Price, Elvin T; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

2013-01-01

Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

On Becoming Trauma-Informed: Role of the Adverse Childhood Experiences Survey in Tertiary Child and Adolescent Mental Health Services and the Association with Standard Measures of Impairment and Severity

PubMed Central

Rahman, Abdul; Perri, Andrea; Deegan, Avril; Kuntz, Jennifer; Cawthorpe, David

2018-01-01

Context There is a movement toward trauma-informed, trauma-focused psychiatric treatment. Objective To examine Adverse Childhood Experiences (ACE) survey items by sex and by total scores by sex vs clinical measures of impairment to examine the clinical utility of the ACE survey as an index of trauma in a child and adolescent mental health care setting. Design Descriptive, polychoric factor analysis and regression analyses were employed to analyze cross-sectional ACE surveys (N = 2833) and registration-linked data using past admissions (N = 10,400) collected from November 2016 to March 2017 related to clinical data (28 independent variables), taking into account multicollinearity. Results Distinct ACE items emerged for males, females, and those with self-identified sex and for ACE total scores in regression analysis. In hierarchical regression analysis, the final models consisting of standard clinical measures and demographic and system variables (eg, repeated admissions) were associated with substantial ACE total score variance for females (44%) and males (38%). Inadequate sample size foreclosed on developing a reduced multivariable model for the self-identified sex group. Conclusion The ACE scores relate to independent clinical measures and system and demographic variables. There are implications for clinical practice. For example, a child presenting with anxiety and a high ACE score likely requires treatment that is different from a child presenting with anxiety and an ACE score of zero. The ACE survey score is an important index of presenting clinical status that guides patient care planning and intervention in the progress toward a trauma-focused system of care. PMID:29401055

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PubMed Central

Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

2017-01-01

Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

2017-01-01

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

Factors influencing the perceived quality of clinical supervision of occupational therapists in a large Australian state.

PubMed

Martin, Priya; Kumar, Saravana; Lizarondo, Lucylynn; Tyack, Zephanie

2016-10-01

Clinical supervision is important for effective health service delivery, professional development and practice. Despite its importance there is a lack of evidence regarding the factors that improve its quality. This study aimed to investigate the factors that influence the quality of clinical supervision of occupational therapists employed in a large public sector health service covering mental health, paediatrics, adult physical and other practice areas. A mixed method, sequential explanatory study design was used consisting of two phases. This article reports the quantitative phase (Phase One) which involved administration of the Manchester Clinical Supervision Scale (MCSS-26) to 207 occupational therapists. Frequency of supervision sessions, choice of supervisor and the type of supervision were found to be the predictor variables with a positive and significant influence on the quality of clinical supervision. Factors such as age, length of supervision and the area of practice were found to be the predictor variables with a negative and significant influence on the quality of clinical supervision. Factors that influence the perceived quality of clinical supervision among occupational therapists have been identified. High quality clinical supervision is an important component of clinical governance and has been shown to be beneficial to practitioners, patients and the organisation. Information on factors that make clinical supervision effective identified in this study can be added to existing supervision training and practices to improve the quality of clinical supervision. © 2016 Occupational Therapy Australia.

A Call to Standardize Preanalytic Data Elements for Biospecimens, Part II.

PubMed

Robb, James A; Bry, Lynn; Sluss, Patrick M; Wagar, Elizabeth A; Kennedy, Mary F

2015-09-01

Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Additional clinical preanalytic variables are the focus of this continuing study. To complete the identification of the essential preanalytic variables (data fields) that can, and in some instances should, be attached to every collected biospecimen by adding the additional specific variables for clinical chemistry and microbiology to our original 170 variables. The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a second Biorepository Working Group to complete the list of preanalytic variables for annotating biospecimens. Members of the second Biorepository Working Group are experts in clinical pathology and microbiology. Additional preanalytic area-specific variables were identified and ranked along with definitions and potential negative impacts if the variable is not attached to the biospecimen. The draft manuscript was reviewed by additional national and international stakeholders. Four additional required preanalytic variables were identified specifically for clinical chemistry and microbiology biospecimens that can be used as a guide for site-specific implementation into patient care and research biorepository processes. In our collective experience, selecting which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research is often difficult. The additional ranked list should be of practical benefit when selecting preanalytic variables for a given biospecimen collection.

Quality assessment of osteoporosis clinical practice guidelines for physical activity and safe movement: an AGREE II appraisal.

PubMed

Armstrong, James Jacob; Rodrigues, Isabel Braganca; Wasiuta, Tom; MacDermid, Joy C

2016-01-01

Many osteoporosis clinical practice guidelines are published, and the extent to which physical activity and safe movement is addressed varies. To better inform clinical decision-making, a quality assessment and structured analysis of recommendations was undertaken. Guideline quality varied substantially, and improvement is necessary in physical activity and safe movement recommendations. The purpose of the present study is to survey available osteoporosis clinical practice guidelines (CPGs) containing physical activity and safe movement recommendations in order to assess the methodological quality with which they were developed. An analysis of the various physical activity and safe movement recommendations was conducted to determine variability between CPGs. An online literature search revealed 19 CPGs meeting our inclusion criteria. Three independent scorers evaluated CPG quality using the Appraisal of Guidelines for Research and Evaluation version II (AGREE II) instrument. Two separate individuals used a standard table to extract relevant recommendations. Intra-reviewer AGREE II score agreement ranged from fair to good (intra-class correlation coefficient (ICC) = 0.34 to 0.65). The quality of the 19 included CPGs was variable (AGREE sub-scores: 14 to 100%). CPGs scored higher in the "scope and purpose" and "clarity of presentation" domains. They scored the lowest in "applicability" and "editorial independence." Four CPGs were classified as high quality, ten average quality, and five low quality. Most CPGs recommended weight-bearing, muscle-strengthening, and resistance exercises. Information on exercise dosage, progression, and contraindications was often absent. Immobility and movements involving spinal flexion and/or torsion were discouraged. There were several high-quality CPGs; however, variability in quality and lack of specific parameters for implementation necessitates caution and critical examination by readers. CPG development groups should pay special attention to the clinical applicability of their CPGs as well as fully disclosing conflicts of interest. CPGs were in general an agreement regarding safe physical activity and safe movement recommendations. However, recommendations were often vague and the more specific recommendations were inconsistent between CPGs.

The Impact of Clinical Information on the Assessment of Endoscopic Activity: Characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS].

PubMed

Travis, Simon P L; Schnell, Dan; Feagan, Brian G; Abreu, Maria T; Altman, Douglas G; Hanauer, Stephen B; Krzeski, Piotr; Lichtenstein, Gary R; Marteau, Philippe R; Mary, Jean-Yves; Reinisch, Walter; Sands, Bruce E; Schnell, Patrick; Yacyshyn, Bruce R; Colombel, Jean-Frédéric; Bernhardt, Christian A; Sandborn, William J

2015-08-01

To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers']. Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information. A total of 21 virtual Central Reader Groups [CRGs], of three blinded readers, were created. Agreement criteria were pre-specified. Kappa [κ] statistics quantified intra- and inter-reader variability. Mean UCEIS scores did not differ between blinded and unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD] were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were similar [UCEIS: p ≥ 0.55; VAS: p ≥ 0.07]. Intra- [κ 0.47-0.74] and inter-reader [κ 0.40-0.53] variability for items and full UCEIS was 'moderate'-to-'substantial', with no significant differences except for intra-reader variability for erosions and ulcers [κ blinded: 0.47 vs unblinded: 0.74; p 0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs 0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]. The UCEIS is minimally affected by knowledge of clinical details, strongly correlates with patient-reported symptoms, and is a suitable instrument for trials. CRGs performed better than individuals. © European Crohn’s and Colitis Organisation 2015.

High Variability in Outcome Reporting Patterns in High-Impact ACL Literature.

PubMed

Makhni, Eric C; Padaki, Ajay S; Petridis, Petros D; Steinhaus, Michael E; Ahmad, Christopher S; Cole, Brian J; Bach, Bernard R

2015-09-16

ACL (anterior cruciate ligament) reconstruction is one of the most commonly performed and studied procedures in modern sports medicine. A multitude of objective and subjective patient outcome measures exists; however, nonstandardized reporting patterns of these metrics may create challenges in objectively analyzing pooled results from different studies. The goal of this study was to document the variability in outcome reporting patterns in high-impact orthopaedic studies of ACL reconstruction. All clinical studies pertaining to ACL reconstruction in four high-impact-factor orthopaedic journals over a five-year period were reviewed. Biomechanical, basic science, and imaging studies were excluded, as were studies with fewer than fifty patients, yielding 119 studies for review. Incorporation of various objective and subjective outcomes was noted for each study. Substantial variability in reporting of both objective and subjective measures was noted in the study cohort. Although a majority of studies reported instrumented laxity findings, there was substantial variability in the type and method of laxity reporting. Most other objective outcomes, including range of motion, strength, and complications, were reported in <50% of all studies. Return to pre-injury level of activity was infrequently reported (24% of studies), as were patient satisfaction and pain assessment following surgery (8% and 13%, respectively). Of the patient-reported outcomes, the International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores were most often reported (71%, 63%, and 42%, respectively). Substantial variability in outcome reporting patterns exists among high-impact studies of ACL reconstruction. Such variability may create challenges in interpreting results and pooling them across different studies. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Probabilistic modeling of anatomical variability using a low dimensional parameterization of diffeomorphisms.

PubMed

Zhang, Miaomiao; Wells, William M; Golland, Polina

2017-10-01

We present an efficient probabilistic model of anatomical variability in a linear space of initial velocities of diffeomorphic transformations and demonstrate its benefits in clinical studies of brain anatomy. To overcome the computational challenges of the high dimensional deformation-based descriptors, we develop a latent variable model for principal geodesic analysis (PGA) based on a low dimensional shape descriptor that effectively captures the intrinsic variability in a population. We define a novel shape prior that explicitly represents principal modes as a multivariate complex Gaussian distribution on the initial velocities in a bandlimited space. We demonstrate the performance of our model on a set of 3D brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our model yields a more compact representation of group variation at substantially lower computational cost than the state-of-the-art method such as tangent space PCA (TPCA) and probabilistic principal geodesic analysis (PPGA) that operate in the high dimensional image space. Copyright © 2017 Elsevier B.V. All rights reserved.

Central venous access and handwashing: variability in policies and practices.

PubMed

Galway, Robyn; Harrod, Mary Ellen; Crisp, Jackie; Donnellan, Robyn; Hardy, Jan; Harvey, Alice; Maurice, Lucy; Petty, Sheila; Senner, Anne

2003-12-01

This study examined variability in handwashing policy between hospitals, variability in handwashing practices in nurses and how practice differed from policy in tertiary paediatric hospitals in Australia and New Zealand. Eight of the possible nine major paediatric hospitals provided a copy of their handwashing and/or central venous access device (CVAD) policies, and 67 nurses completed a survey on their handwashing practices associated with CVAD management. A high degree of variability was found in relation to all the questions posed in the study. There was little consistency between policies and little agreement between policies and clinical practice, with many nurses washing for longer than required by policy. Rigour of handwashing also varied according to the procedure undertaken and the type of CVAD with activities undertaken farther from the insertion site of the device more likely to be performed using a clean rather than an aseptic handwashing technique. As both patients and nursing staff move within and between hospitals, a uniform and evidence-based approach to handwashing is highly desirable.

[Four years of raw mortality in an intensive care unit].

PubMed

Loria, Alvar; Rosas-Baruch, Agustina; Posadas, Juan Gabriel; Domínguez-Cherit, Guillermo; Rivero-Sigarroa, Eduardo

2008-01-01

To characterize magnitude and variability of raw mortality in a Mexican Intensive Care Unit (ICU). Demographic and clinical data were analyzed in 1,746 patients discharged from the ICU of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. The data was obtained from an administrative database and covered four years (2003-2006). Overall ICU-mortality was 23% (410/1746) and was associated with two binary variables (higher mortality in weekend admissions and non-surgical cases) and three multicategorical variables (gradient of increasing mortality with increasing age, increasing diagnostic risk and increasing number of high-rish diagnoses). First biennium mortality was significantly higher than in the second biennium (29% us 19%). This higher mortality was not associated with the high risk categories of the five variables described above nor with other ICU-variables such as number of nurses and admission and discharge criteria. The only biennium difference was a higher number of physicians (specialists + residents) in the second biennium (16-20 versus 14-15 in the first). The four-year long-term ICU-mortality showed a significant decrease in the second biennium. Number of physicians was the only variable associated with the decreased mortality.

Dental occlusion and temporomandibular disorders.

PubMed

Stone, J Caitlin; Hannah, Andrew; Nagar, Nathan

2017-10-27

Data sourcesMedline, Scopus and Google Scholar.Study selectionTwo reviewers selected studies independently. English language clinical studies assessing the association between temporomandibular disorders (TMD) and features of dental occlusion were considered.Data extraction and synthesisStudy quality was assessed based on the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was presented.ResultsIn all 25 studies (17 case-control, eight comparative) were included. Overall there was a high variability between occlusal features and TMD diagnosis. Findings were consistent with a lack of clinically relevant association between TMD and dental occlusion. Only two studies were associated with TMD in the majority (≥50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses.ConclusionsThe findings support the absence of a disease-specific association, there is no ground to hypothesise a major role for dental occlusion in the pathophysiology of TMDs. Dental clinicians are thus encouraged to move forward and abandon the old-fashioned gnathological paradig.

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

PubMed

Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

2015-01-01

It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-English speakers attend gastroenterology clinic appointments at higher rates than English speakers in a vulnerable patient population

PubMed Central

Sewell, Justin L.; Kushel, Margot B.; Inadomi, John M.; Yee, Hal F.

2009-01-01

Goals We sought to identify factors associated with gastroenterology clinic attendance in an urban safety net healthcare system. Background Missed clinic appointments reduce the efficiency and availability of healthcare, but subspecialty clinic attendance among patients with established healthcare access has not been studied. Study We performed an observational study using secondary data from administrative sources to study patients referred to, and scheduled for an appointment in, the adult gastroenterology clinic serving the safety net healthcare system of San Francisco, California. Our dependent variable was whether subjects attended or missed a scheduled appointment. Analysis included multivariable logistic regression and classification tree analysis. 1,833 patients were referred and scheduled for an appointment between 05/2005 and 08/2006. Prisoners were excluded. All patients had a primary care provider. Results 683 patients (37.3%) missed their appointment; 1,150 (62.7%) attended. Language was highly associated with attendance in the logistic regression; non-English speakers were less likely than English speakers to miss an appointment (adjusted odds ratio 0.42 [0.28,0.63] for Spanish, 0.56 [0.38,0.82] for Asian language, p < 0.001). Other factors were also associated with attendance, but classification tree analysis identified language to be the most highly associated variable. Conclusions In an urban safety net healthcare population, among patients with established healthcare access and a scheduled gastroenterology clinic appointment, not speaking English was most strongly associated with higher attendance rates. Patient related factors associated with not speaking English likely influence subspecialty clinic attendance rates, and these factors may differ from those affecting general healthcare access. PMID:19169147

The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer

NASA Astrophysics Data System (ADS)

Tilly, N.; Johansson, J.; Isacsson, U.; Medin, J.; Blomquist, E.; Grusell, E.; Glimelius, B.

2005-06-01

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the αref/βref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE = 1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study—based on in vitro data since human tissue RBE values are scarce and have large uncertainties—can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

PubMed

Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2018-05-01

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

Measuring the degree of integrated tuberculosis and HIV service delivery in Cape Town, South Africa.

PubMed

Uyei, Jennifer; Coetzee, David; Macinko, James; Weinberg, Sharon L; Guttmacher, Sally

2014-01-01

To address the considerable tuberculosis (TB)/HIV co-infected population in Cape Town, a number of clinics have made an effort of varying degrees to integrate TB and HIV services. This article describes the development of a theory-based survey instrument designed to quantify the extent to which services were integrated in 33 clinics and presents the results of the survey. Using principal factor analysis, eight factors were extracted and used to make comparisons across three types of clinics: co-located TB and antiretroviral therapy (ART) services, clinics with TB services only and clinics with ART only. Clinics with co-located services scored highest on measures related to integrated TB/ART service delivery compared to clinics with single services, but within group variability was high indicating that co-location of TB and ART services is a necessary but insufficient condition for integrated service delivery. In addition, we found almost all clinics with only TB services in our sample had highly integrated pre-ART services, suggesting that integration of these services across a large number of clinics is feasible and acceptable to clinic staff. TB clinics with highly integrated pre-ART services appear to be efficient sites for introducing ART given that co-infected patients are already engaged in care, and may potentially facilitate earlier access to treatment and minimize loss to follow-up.

Clinical phenotypes and the biological parameters of Congolese patients suffering from sickle cell anemia: A first report from Central Africa.

PubMed

Mikobi, Tite M; Lukusa Tshilobo, Prosper; Aloni, Michel N; Akilimali, Pierre Z; Mvumbi-Lelo, Georges; Mbuyi-Muamba, Jean Marie

2017-11-01

The influence of phenotype on the clinical course and laboratory features of sickle cell anemia (SCA) is rarely described in sub-Saharan Africa. A cross-sectional study was conducted in Kinshasa. A clinical phenotype score was built up. The following definitions were applied: asymptomatic clinical phenotype (ACP; score≤5), moderate clinical phenotype (MCP; score between 6 and 15), and severe clinical phenotype (SCP; score≥16). ANOVA test were used to compare differences among categorical variables. We have studied 140 patients. The mean body mass index (BMI) value of three groups was lower (<25 kg/m 2 ) than the limit defining overweight. BMI of the subjects with ACP was significantly higher than those of other phenotypes (P<.05). Sickle cell patients with ACP have a high mean steady-state hemoglobin concentration compared to those with MCP and SCP (P<.001). A significant elevated baseline leukocyte count is associated with SCP (P<.001). Fetal Hemoglobin (HbF) was significantly higher in ACP. Significant elevation of alpha 1 and alpha 2 globulins in SCP were observed. In our study, fetal hemoglobin has an influence on the clinical severity and the biological parameters of SCA. The study provides data concerning the sickle cell anemia clinical and biological variability in our midst. © 2017 Wiley Periodicals, Inc.

Application of lean methods improves surgical clinic experience.

PubMed

Waldhausen, John H T; Avansino, Jeffrey R; Libby, Arlene; Sawin, Robert S

2010-07-01

A quality visit in high volume surgery clinics is challenging. There is variability in numbers of patients seen and care provider behavior. Documentation, regulatory and compliance issues and computerization of patient care systems may decrease clinic efficiency and throughput. We tried to reduce variability and improve patient experience. Baseline data included: patients seen, time in exam rooms, and spent with providers, and patient satisfaction surveys. Two Rapid Process Improvement Workshops (RPIWs) were conducted to apply lean methods. 5S techniques helped standardize exam rooms. Similar data were collected at 30 days, 60 days, and 1 year. Satisfaction surveys were followed at 6 months and 1 year. Median pre-RPIW room time was 49 minutes. Post-RPIW times were 33 minutes at 30 days, 41 minutes at 60 days, and 42 minutes at 1 year. Face to face provider-patient time increased 30% to 61% at 30 days, 58% at 60 days, and 59% at 1 year. The median number of patients in a 4-hour clinic increased from 10 to 12. Satisfaction survey Problem Scores improved and were sustained. Lean methodology may be used to improve clinic efficiency as well as patient and staff's experience. Copyright 2010. Published by Elsevier Inc.

Psychosis prediction and clinical utility in familial high-risk studies: Selective review, synthesis, and implications for early detection and intervention

PubMed Central

Shah, Jai L.; Tandon, Neeraj; Keshavan, Matcheri S.

2016-01-01

Aim Accurate prediction of which individuals will go on to develop psychosis would assist early intervention and prevention paradigms. We sought to review investigations of prospective psychosis prediction based on markers and variables examined in longitudinal familial high-risk (FHR) studies. Methods We performed literature searches in MedLine, PubMed and PsycINFO for articles assessing performance characteristics of predictive clinical tests in FHR studies of psychosis. Studies were included if they reported one or more predictive variables in subjects at FHR for psychosis. We complemented this search strategy with references drawn from articles, reviews, book chapters and monographs. Results Across generations of familial high-risk projects, predictive studies have investigated behavioral, cognitive, psychometric, clinical, neuroimaging, and other markers. Recent analyses have incorporated multivariate and multi-domain approaches to risk ascertainment, although with still generally modest results. Conclusions While a broad range of risk factors has been identified, no individual marker or combination of markers can at this time enable accurate prospective prediction of emerging psychosis for individuals at FHR. We outline the complex and multi-level nature of psychotic illness, the myriad of factors influencing its development, and methodological hurdles to accurate and reliable prediction. Prospects and challenges for future generations of FHR studies are discussed in the context of early detection and intervention strategies. PMID:23693118

Cytokines Synergize to Combat Metastatic Neuroblastoma | Center for Cancer Research

Cancer.gov

Neuroblastoma is the most common extracranial solid tumor in children, and clinical outcomes of patients with this disease are quite variable. Prognosis is particularly poor for patients with high-risk tumors (classification based on patients’ age, extent of disease spread, and other biological features).

Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting

PubMed Central

Tschulik, Claudia; Piossek, Christine; Bet, Jeannette; Yamamoto, Tori N.; Schiemann, Matthias; Neuenhahn, Michael; Martin, Klaus; Schlapschy, Martin; Skerra, Arne; Schmidt, Thomas; Edinger, Matthias; Riddell, Stanley R.; Germeroth, Lothar; Busch, Dirk H.

2012-01-01

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research. PMID:22545138

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

On assessing the quality of physicians' clinical judgment: the search for outcome variables.

PubMed

Wainer, Howard; Mee, Janet

2004-12-01

A primary question that must be resolved in the development of tasks to assess the quality of physicians' clinical judgment is, "What is the outcome variable?" One natural choice would seem to be the correctness of the clinical decision. In this article, we use data on the diagnosis of urinary tract infections among young girls to illustrate why, in many clinical situations, this is not a useful variable. We propose instead a judgment weighted by the relative costs of an error. This variable has the disadvantage of requiring expert judgment for scoring, but the advantage of measuring the construct of interest.

Clinical Correlates of Planned and Unplanned Suicide Attempts.

PubMed

Chaudhury, Sadia R; Singh, Tanya; Burke, Ainsley; Stanley, Barbara; Mann, J John; Grunebaum, Michael; Sublette, M Elizabeth; Oquendo, Maria A

2016-11-01

Suicide attempters differ in the degree of planning for their suicide attempts. The purpose of this study was to identify differences between individuals who make planned (≥3 hours of planning) and unplanned (<3 hours of planning) suicide attempts. Depressed suicide attempters (n = 110) were compared based on degree of planning of their most recent suicide attempt on demographic and clinical variables. Participants who made planned suicide attempts were more likely to have family history of completed suicide, more severe and frequent suicidal ideation, greater trait impulsivity, and greater suicidal intent and more severe medical consequences for both their most recent and most serious suicide attempts. These results suggest clear clinical differences based on the degree of suicide attempt planning. Severe suicidal ideation, high suicide intent, family history of suicide completion, and high levels of motor impulsivity contribute to a phenotype that is at greater risk of planned, highly lethal suicide attempts.

Review and classification of variability analysis techniques with clinical applications.

PubMed

Bravi, Andrea; Longtin, André; Seely, Andrew J E

2011-10-10

Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis.

Review and classification of variability analysis techniques with clinical applications

PubMed Central

2011-01-01

Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis. PMID:21985357

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

PubMed Central

DePalma, Ralph G.; Shamayeva, Galina; Chow, Bruce K.

2013-01-01

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins. PMID:23409890

Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients?

PubMed Central

2014-01-01

Introduction Prolonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown. Methods We enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models. Results Of 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively. Conclusions Altered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability. Trial registration ClinicalTrials.gov NCT01237886. Registered 13 October 2010. PMID:24713049

System for selecting relevant information for decision support.

PubMed

Kalina, Jan; Seidl, Libor; Zvára, Karel; Grünfeldová, Hana; Slovák, Dalibor; Zvárová, Jana

2013-01-01

We implemented a prototype of a decision support system called SIR which has a form of a web-based classification service for diagnostic decision support. The system has the ability to select the most relevant variables and to learn a classification rule, which is guaranteed to be suitable also for high-dimensional measurements. The classification system can be useful for clinicians in primary care to support their decision-making tasks with relevant information extracted from any available clinical study. The implemented prototype was tested on a sample of patients in a cardiological study and performs an information extraction from a high-dimensional set containing both clinical and gene expression data.

Effect of mixed mutans streptococci colonization on caries development.

PubMed

Seki, M; Yamashita, Y; Shibata, Y; Torigoe, H; Tsuda, H; Maeno, M

2006-02-01

To evaluate the clinical importance of mixed mutans streptococci colonization in predicting caries in preschool children. Caries prevalence was examined twice, with a 6-month interval, in 410 preschool children aged 3-4 years at baseline. A commercial strip method was used to evaluate the mutans streptococci score in plaque collected from eight selected interdental spaces and in saliva. Mutans streptococci typing polymerase chain reaction (PCR) assays (Streptococcus sobrinus and Streptococcus mutans, including serotypes c, e, and f) were performed using colonies on the strips as template. Twenty variables were examined in a univariate analysis to predict caries development: questionnaire variables, results of clinical examination, mutans streptococci scores, and PCR detection of S. sobrinus and S. mutans (including serotypes c, e, and f). Sixteen variables showed statistically significant associations (P < 0.04) in the univariate analysis. However, when entered into a logistic regression, only five variables remained significant (P < 0.05): caries experience at baseline; mixed colonization of S. sobrinus and S. mutans including S. mutans serotypes; high plaque mutans streptococci score; habitual use of sweet drinks; and nonuse of fluoride toothpaste. 'Mixed mutans streptococci colonization' is a novel measure correlated with caries development in their primary dentition.

Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

PubMed

Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

2016-02-28

The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

EDUCORE project: a clinical trial, randomised by clusters, to assess the effect of a visual learning method on blood pressure control in the primary healthcare setting

PubMed Central

2010-01-01

Background High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD). European hypertension and cardiology societies as well as expert committees on CVD prevention recommend stratifying cardiovascular risk using the SCORE method, the modification of lifestyles to prevent CVD, and achieving good control over risk factors. The EDUCORE (Education and Coronary Risk Evaluation) project aims to determine whether the use of a cardiovascular risk visual learning method - the EDUCORE method - is more effective than normal clinical practice in improving the control of blood pressure within one year in patients with poorly controlled hypertension but no background of CVD; Methods/Design This work describes a protocol for a clinical trial, randomised by clusters and involving 22 primary healthcare clinics, to test the effectiveness of the EDUCORE method. The number of patients required was 736, all between 40 and 65 years of age (n = 368 in the EDUCORE and control groups), all of whom had been diagnosed with HBP at least one year ago, and all of whom had poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic ≥ 90 mmHg). All personnel taking part were explained the trial and trained in its methodology. The EDUCORE method contemplates the visualisation of low risk SCORE scores using images embodying different stages of a high risk action, plus the receipt of a pamphlet explaining how to better maintain cardiac health. The main outcome variable was the control of blood pressure; secondary outcome variables included the SCORE score, therapeutic compliance, quality of life, and total cholesterol level. All outcome variables were measured at the beginning of the experimental period and again at 6 and 12 months. Information on sex, age, educational level, physical activity, body mass index, consumption of medications, change of treatment and blood analysis results was also recorded; Discussion The EDUCORE method could provide a simple, inexpensive means of improving blood pressure control, and perhaps other health problems, in the primary healthcare setting; Trial registration The trial was registered with ClinicalTrials.gov, number NCT01155973 [http://ClinicalTrials.gov]. PMID:20673325

Highly Discriminatory Variable-Number Tandem-Repeat Markers for Genotyping of Trichophyton interdigitale Strains

PubMed Central

Drira, Ines; Hadrich, Ines; Neji, Sourour; Mahfouth, Nedia; Trabelsi, Houaida; Sellami, Hayet; Makni, Fattouma

2014-01-01

Trichophyton interdigitale is the second most frequent cause of superficial fungal infections of various parts of the human body. Studying the population structure and genotype differentiation of T. interdigitale strains may lead to significant improvements in clinical practice. The present study aimed to develop and select suitable variable-number tandem-repeat (VNTR) markers for 92 clinical strains of T. interdigitale. On the basis of an analysis of four VNTR markers, four to eight distinct alleles were detected for each marker. The marker with the highest discriminatory power had eight alleles and a D value of 0.802. The combination of all four markers yielded a D value of 0.969 with 29 distinct multilocus genotypes. VNTR typing revealed the genetic diversity of the strains, identifying three populations according to their colonization sites. A correlation between phenotypic characteristics and multilocus genotypes was observed. Seven patients harbored T. interdigitale strains with different genotypes. Typing of clinical T. interdigitale samples by VNTR markers displayed excellent discriminatory power and 100% reproducibility. PMID:24989614

Diagnosis of Swallowing Disorders: How We Interpret Pharyngeal Manometry.

PubMed

Cock, Charles; Omari, Taher

2017-03-01

We provide an overview of the clinical application of novel pharyngeal high-resolution impedance manometry (HRIM) with pressure flow analysis (PFA) in our hands with example cases. In our Centre, we base our interpretation of HRIM recordings upon a qualitative assessment of pressure-impedance waveforms during individual swallows, as well as a quantitative assessment of averaged PFA swallow function variables. We provide a description of two global swallowing efficacy measures, the swallow risk index (SRI), reflecting global swallowing dysfunction (higher SRI = greater aspiration risk) and the post-swallow impedance ratio (PSIR) detecting significant post-swallow bolus residue. We describe a further eight swallow function variables specific to the hypopharynx and upper esophageal sphincter (UES), assessing hypo-pharyngeal distension pressure, contractility, bolus presence and flow timing, and UES basal tone, relaxation, opening and contractility. Pharyngeal HRIM has now come of age, being applicable for routine clinical practice to assess the biomechanics of oropharyngeal swallowing dysfunction. In the future, it may guide treatment strategies and allow more objective longitudinal follow-up on clinical outcomes.

Correlates of Successful Response to a Behavioral Weight Control Clinic.

ERIC Educational Resources Information Center

And Others; Gormally, Jim

1980-01-01

Initial weight-loss success was correlated with two severity variables. Persons reporting frequent binge eating and histories of previous dieting weight loss lost the most weight. Persons who were successful at maintenance used frequent exercise. Those who relapsed reported high levels of stress during follow-up. (Author)

Big data and computational biology strategy for personalized prognosis.

PubMed

Ow, Ghim Siong; Tang, Zhiqun; Kuznetsov, Vladimir A

2016-06-28

The era of big data and precision medicine has led to accumulation of massive datasets of gene expression data and clinical information of patients. For a new patient, we propose that identification of a highly similar reference patient from an existing patient database via similarity matching of both clinical and expression data could be useful for predicting the prognostic risk or therapeutic efficacy.Here, we propose a novel methodology to predict disease/treatment outcome via analysis of the similarity between any pair of patients who are each characterized by a certain set of pre-defined biological variables (biomarkers or clinical features) represented initially as a prognostic binary variable vector (PBVV) and subsequently transformed to a prognostic signature vector (PSV). Our analyses revealed that Euclidean distance rather correlation distance measure was effective in defining an unbiased similarity measure calculated between two PSVs.We implemented our methods to high-grade serous ovarian cancer (HGSC) based on a 36-mRNA predictor that was previously shown to stratify patients into 3 distinct prognostic subgroups. We studied and revealed that patient's age, when converted into binary variable, was positively correlated with the overall risk of succumbing to the disease. When applied to an independent testing dataset, the inclusion of age into the molecular predictor provided more robust personalized prognosis of overall survival correlated with the therapeutic response of HGSC and provided benefit for treatment targeting of the tumors in HGSC patients.Finally, our method can be generalized and implemented in many other diseases to accurately predict personalized patients' outcomes.

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

PubMed

Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

2015-01-01

To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

PubMed Central

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

Dolichoectatic aneurysms of the vertebrobasilar system: clinical and radiographic factors that predict poor outcomes.

PubMed

Xu, David S; Levitt, Michael R; Kalani, M Yashar S; Rangel-Castilla, Leonardo; Mulholland, Celene B; Abecassis, Isaac J; Morton, Ryan P; Nerva, John D; Siddiqui, Adnan H; Levy, Elad I; Spetzler, Robert F; Albuquerque, Felipe C; McDougall, Cameron G

2018-02-01

OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

[Variability in the in-hospital management of acute myocardial infarction in Spain. IBERICA Study (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda)].

PubMed

Fiol, M; Cabadés, A; Sala, J; Marrugat, J; Elosua, R; Vega, G; José Tormo Díaz, M; Segura, A; Aldasoro, E; Moreno-Iribas, C; Muñiz, J; Hurtado de Saracho, I; García, J

2001-04-01

Introduction and objective. Although some in-hospital studies have described the management of acute myocardial infarction (MI) patients in Spain, none has been able to guarantee the exhaustiveness of patient registry. This study sought to determine the clinical characteristics and in-hospital management of patients with MI in eight Spanish population registries.Methods. The IBERICA study is a population-based MI registry carried out in the 25 to 74 year-old population, in eight Spanish regions in 1997. A standardized methodology was used to register and investigate all MI arriving alive to a hospital. Clinical characteristics, cardiovascular risk factors prevalence, pharmacological treatment, invasive and non-invasive procedures performed and complications at 28 days of evolution were recorded. A descriptive analysis was performed and the variation coefficient (VC) was calculated.Results. In 1997, 4,041 MI patients were registered, 79.9% were men with a mean age of 61.1 years. Although 10.9% (95% CI: 9.9-11.9%) were not admitted to the coronary care unit, a large variability existed among different areas (VC = 53%). There was a high variability in the utilization and performance of non-invasive and invasive procedures among regions, as well as in the use of pharmacological treatment. Only the use of antiaggregants (91.5%) and thrombolytic therapy (41.8%) showed a low variability (VC < 10%). Twenty-eight day mortality was 16.2% (95% CI: 15.1-17.4%) with a high variability being observed among the different regions (VC = 20.6%).Conclusion. Patient characteristics vary among the different Spanish regions. The differences in management and prognosis suggest a lack of equality in the health care provided to MI patients in the different regions in Spain.

Clinical research in a hospital--from the lone rider to teamwork.

PubMed

Hannisdal, E

1996-01-01

Clinical research of high international standard is very demanding and requires clinical data of high quality, software, hardware and competence in research design and statistical treatment of data. Most busy clinicians have little time allocated for clinical research and this increases the need for a potent infrastructure. This paper describes how the Norwegian Radium Hospital, a specialized cancer hospital, has reorganized the clinical research process. This includes a new department, the Clinical Research Office, which serves the formal framework, a central Diagnosis Registry, clinical databases and multicentre studies. The department assists about 120 users, mainly clinicians. Installation of a network software package with over 10 programs has strongly provided an internal standardization, reduced the costs and saved clinicians a great deal of time. The hospital is building up about 40 diagnosis-specific clinical databases with up to 200 variables registered. These databases are shared by the treatment group and seem to be important tools for quality assurance. We conclude that the clinical research process benefits from a firm infrastructure facilitating teamwork through extensive use of modern information technology. We are now ready for the next phase, which is to work for a better external technical framework for cooperation with other institutions throughout the world.

Variable mechanical ventilation

PubMed Central

Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

2017-01-01

Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

Assessing national provision of care: variability in bariatric clinical care pathways.

PubMed

Telem, Dana A; Majid, Saniea F; Powers, Kinga; DeMaria, Eric; Morton, John; Jones, Daniel B

2017-02-01

The American Society for Metabolic and Bariatric Surgery (ASMBS) Quality Improvement and Patient Safety (QIPS) Committee hypothesized that collecting and sharing clinical pathways could provide a valuable resource to new and existing bariatric programs. To shed light on the variability in practice patterns across the country by analyzing pathways. United States Centers of Excellence METHODS: From June 2014 to April 2015, clinical pathways pertaining to preoperative, intraoperative, and postoperative management of bariatric patients were solicited from the ASMBS executive council (EC), QIPS committee members, and state chapter presidents. Pathways were de-identified and then analyzed based on predetermined metrics pertaining to preoperative, intraoperative, and postoperative care. Concordance and discordance were then analyzed. In total, 31 pathways were collected; response rate was 80% from the EC, 77% from the QIPS committee, and 21% from state chapter presidents. The number of pathways sent in ranged from 1 to 10 with a median of 3 pathways per individual or institution. The majority of pathways centered on perioperative care (80%). Binary assessment (presence or absence) of variables found a high concordance (defined by greater than 65% of pathways accounting for that parameter) in only 6 variables: nutritional evaluation, psychological evaluation, intraoperative venous thromboembolism (VTE) prophylaxis, utilization of antiemetics in the postoperative period, a dedicated pain pathway, and postoperative laboratory evaluation. There is considerable national variation in clinical pathways among practicing bariatric surgeons. Most pathways center on Metabolic and Bariatric Surgery Accredited Quality Improvement Program (MBSAQIP) accreditation parameters, patient satisfaction, or Surgical Care Improvement Protocol (SCIP) measures. These pathways provide a path toward standardization of improved care. Copyright © 2016. Published by Elsevier Inc.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

PubMed Central

Lin, Jennie; Fernandez, Hilda; Shashaty, Michael G.S.; Negoianu, Dan; Testani, Jeffrey M.; Berns, Jeffrey S.; Parikh, Chirag R.

2015-01-01

Background and objectives Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false–positive rates because of inherent laboratory and biologic variabilities of creatinine. Design, setting, participants, & measurements We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false–positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient’s true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. Results Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false–positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%–8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false–positive AKI diagnosis rate of 30.5% (interquartile range =30.1%–30.9%) versus 2.0% (interquartile range =1.9%–2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). Conclusions Use of small serum creatinine changes to diagnose AKI is limited by high false–positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies. PMID:26336912

False-Positive Rate of AKI Using Consensus Creatinine-Based Criteria.

PubMed

Lin, Jennie; Fernandez, Hilda; Shashaty, Michael G S; Negoianu, Dan; Testani, Jeffrey M; Berns, Jeffrey S; Parikh, Chirag R; Wilson, F Perry

2015-10-07

Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false-positive rates because of inherent laboratory and biologic variabilities of creatinine. We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false-positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient's true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false-positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%-8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false-positive AKI diagnosis rate of 30.5% (interquartile range =30.1%-30.9%) versus 2.0% (interquartile range =1.9%-2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). Use of small serum creatinine changes to diagnose AKI is limited by high false-positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies. Copyright © 2015 by the American Society of Nephrology.

Managing the genomic revolution in cancer diagnostics.

PubMed

Nguyen, Doreen; Gocke, Christopher D

2017-08-01

Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling.

Pharmacogenetics of warfarin: challenges and opportunities

PubMed Central

Ta Michael Lee, Ming; Klein, Teri E

2014-01-01

Since the introduction in the 1950s, warfarin has become the commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial fibrillation or prosthetic heart valve replacement. Warfarin is highly efficacious; however, achieving the desired anticoagulation is difficult because of its narrow therapeutic window and highly variable dose response among individuals. Bleeding is often associated with overdose of warfarin. There is overwhelming evidence that an individual's warfarin maintenance is associated with clinical factors and genetic variations, most notably polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase subunit 1. Numerous dose-prediction algorithms incorporating both genetic and clinical factors have been developed and tested clinically. However, results from major clinical trials are not available yet. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges for the clinical implementation of warfarin pharmacogenetics. PMID:23657428

Baccalaureate nursing students' perceptions of learning and supervision in the clinical environment.

PubMed

Dimitriadou, Maria; Papastavrou, Evridiki; Efstathiou, Georgios; Theodorou, Mamas

2015-06-01

This study is an exploration of nursing students' experiences within the clinical learning environment (CLE) and supervision provided in hospital settings. A total of 357 second-year nurse students from all universities in Cyprus participated in the study. Data were collected using the Clinical Learning Environment, Supervision and Nurse Teacher instrument. The dimension "supervisory relationship (mentor)", as well as the frequency of individualized supervision meetings, were found to be important variables in the students' clinical learning. However, no statistically-significant connection was established between successful mentor relationship and team supervision. The majority of students valued their mentor's supervision more highly than a nurse teacher's supervision toward the fulfillment of learning outcomes. The dimensions "premises of nursing care" and "premises of learning" were highly correlated, indicating that a key component of a quality clinical learning environment is the quality of care delivered. The results suggest the need to modify educational strategies that foster desirable learning for students in response to workplace demands. © 2014 Wiley Publishing Asia Pty Ltd.

Birth Control in Clinical Trials

PubMed Central

Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

2015-01-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

Development of a computer-based clinical decision support tool for selecting appropriate rehabilitation interventions for injured workers.

PubMed

Gross, Douglas P; Zhang, Jing; Steenstra, Ivan; Barnsley, Susan; Haws, Calvin; Amell, Tyler; McIntosh, Greg; Cooper, Juliette; Zaiane, Osmar

2013-12-01

To develop a classification algorithm and accompanying computer-based clinical decision support tool to help categorize injured workers toward optimal rehabilitation interventions based on unique worker characteristics. Population-based historical cohort design. Data were extracted from a Canadian provincial workers' compensation database on all claimants undergoing work assessment between December 2009 and January 2011. Data were available on: (1) numerous personal, clinical, occupational, and social variables; (2) type of rehabilitation undertaken; and (3) outcomes following rehabilitation (receiving time loss benefits or undergoing repeat programs). Machine learning, concerned with the design of algorithms to discriminate between classes based on empirical data, was the foundation of our approach to build a classification system with multiple independent and dependent variables. The population included 8,611 unique claimants. Subjects were predominantly employed (85 %) males (64 %) with diagnoses of sprain/strain (44 %). Baseline clinician classification accuracy was high (ROC = 0.86) for selecting programs that lead to successful return-to-work. Classification performance for machine learning techniques outperformed the clinician baseline classification (ROC = 0.94). The final classifiers were multifactorial and included the variables: injury duration, occupation, job attachment status, work status, modified work availability, pain intensity rating, self-rated occupational disability, and 9 items from the SF-36 Health Survey. The use of machine learning classification techniques appears to have resulted in classification performance better than clinician decision-making. The final algorithm has been integrated into a computer-based clinical decision support tool that requires additional validation in a clinical sample.

Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies.

PubMed

McShane, L M; Clark, L C; Combs, G F; Turnbull, B W

1991-06-01

Procedures for reporting and monitoring the accuracy of biochemical measurements are presented. They are proposed as standard reporting procedures for laboratory assays for epidemiologic and clinical-nutrition studies. The recommended procedures require identification and estimation of all major sources of variability and explanations of laboratory quality control procedures employed. Variance-components techniques are used to model the total variability and calculate a maximum percent error that provides an easily understandable measure of laboratory precision accounting for all sources of variability. This avoids ambiguities encountered when reporting an SD that may taken into account only a few of the potential sources of variability. Other proposed uses of the total-variability model include estimating precision of laboratory methods for various replication schemes and developing effective quality control-checking schemes. These procedures are demonstrated with an example of the analysis of alpha-tocopherol in human plasma by using high-performance liquid chromatography.

What variables can influence clinical reasoning?

PubMed

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-12-01

Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R(2) chnage = 0.46, P Value = 0.000). Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction.

The Analytic Information Warehouse (AIW): a Platform for Analytics using Electronic Health Record Data

PubMed Central

Post, Andrew R.; Kurc, Tahsin; Cholleti, Sharath; Gao, Jingjing; Lin, Xia; Bornstein, William; Cantrell, Dedra; Levine, David; Hohmann, Sam; Saltz, Joel H.

2013-01-01

Objective To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations. Materials and Methods We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs. Results We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers. Discussion and Conclusion A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies. PMID:23402960

Formant Frequencies and Bandwidths in Relation to Clinical Variables in an Obstructive Sleep Apnea Population.

PubMed

Montero Benavides, Ana; Blanco Murillo, José Luis; Fernández Pozo, Rubén; Espinoza Cuadros, Fernando; Torre Toledano, Doroteo; Alcázar-Ramírez, José D; Hernández Gómez, Luis A

2016-01-01

We investigated whether differences in formants and their bandwidths, previously reported comparing small sample population of healthy individuals and patients with obstructive sleep apnea (OSA), are detected on a larger population representative of a clinical practice scenario. We examine possible indirect or mediated effects of clinical variables, which may shed some light on the connection between speech and OSA. In a retrospective study, 241 male subjects suspected to suffer from OSA were examined. The apnea-hypopnea index (AHI) was obtained for every subject using overnight polysomnography. Furthermore, the clinical variables usually reported as predictors of OSA, body mass index (BMI), cervical perimeter, height, weight, and age, were collected. Voice samples of sustained phonations of the vowels /a/, /e/, /i/, /o/, and /u/ were recorded. Formant frequencies F1, F2, and F3 and bandwidths BW1, BW2, and BW3 of the sustained vowels were determined using spectrographic analysis. Correlations among AHI, clinical parameters, and formants and bandwidths were determined. Correlations between AHI and clinical variables were stronger than those between AHI and voice features. AHI only correlates poorly with BW2 of /a/ and BW3 of /e/. A number of further weak but significant correlations have been detected between voice and clinical variables. Most of them were for height and age, with two higher values for age and F2 of /o/ and F2 of /u/. Only few very weak correlations were detected between voice and BMI, weight and cervical perimeter, wich are the clinical variables more correlated with AHI. No significant correlations were detected between AHI and formant frequencies and bandwidths. Correlations between voice and other clinical factors characterizing OSA are weak but highlight the importance of considering indirect or mediated effects of such clinical variables in any research on speech and OSA. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Reliability and validity of a novel Kinect-based software program for measuring posture, balance and side-bending.

PubMed

Grooten, Wilhelmus Johannes Andreas; Sandberg, Lisa; Ressman, John; Diamantoglou, Nicolas; Johansson, Elin; Rasmussen-Barr, Eva

2018-01-08

Clinical examinations are subjective and often show a low validity and reliability. Objective and highly reliable quantitative assessments are available in laboratory settings using 3D motion analysis, but these systems are too expensive to use for simple clinical examinations. Qinematic™ is an interactive movement analyses system based on the Kinect camera and is an easy-to-use clinical measurement system for assessing posture, balance and side-bending. The aim of the study was to test the test-retest the reliability and construct validity of Qinematic™ in a healthy population, and to calculate the minimal clinical differences for the variables of interest. A further aim was to identify the discriminative validity of Qinematic™ in people with low-back pain (LBP). We performed a test-retest reliability study (n = 37) with around 1 week between the occasions, a construct validity study (n = 30) in which Qinematic™ was tested against a 3D motion capture system, and a discriminative validity study, in which a group of people with LBP (n = 20) was compared to healthy controls (n = 17). We tested a large range of psychometric properties of 18 variables in three sections: posture (head and pelvic position, weight distribution), balance (sway area and velocity in single- and double-leg stance), and side-bending. The majority of the variables in the posture and balance sections, showed poor/fair reliability (ICC < 0.4) and poor/fair validity (Spearman <0.4), with significant differences between occasions, between Qinematic™ and the 3D-motion capture system. In the clinical study, Qinematic™ did not differ between people with LPB and healthy for these variables. For one variable, side-bending to the left, there was excellent reliability (ICC =0.898), excellent validity (r = 0.943), and Qinematic™ could differentiate between LPB and healthy individuals (p = 0.012). This paper shows that a novel software program (Qinematic™) based on the Kinect camera for measuring balance, posture and side-bending has poor psychometric properties, indicating that the variables on balance and posture should not be used for monitoring individual changes over time or in research. Future research on the dynamic tasks of Qinematic™ is warranted.

[Assessment of the correlation between histological degeneration and radiological and clinical parameters in a series of patients who underwent lumbar disc herniation surgery].

PubMed

Munarriz, Pablo M; Paredes, Igor; Alén, José F; Castaño-Leon, Ana M; Cepeda, Santiago; Hernandez-Lain, Aurelio; Lagares, Alfonso

The use of histological degeneration scores in surgically-treated herniated lumbar discs is not common in clinical practice and its use has been primarily restricted to research. The objective of this study is to evaluate if there is an association between a higher grade of histological degeneration when compared with clinical or radiological parameters. Retrospective consecutive analysis of 122 patients who underwent single-segment lumbar disc herniation surgery. Clinical information was available on all patients, while the histological study and preoperative magnetic resonance imaging were also retrieved for 75 patients. Clinical variables included age, duration of symptoms, neurological deficits, or affected deep tendon reflex. The preoperative magnetic resonance imaging was evaluated using Modic and Pfirrmann scores for the affected segment by 2 independent observers. Histological degeneration was evaluated using Weiler's score; the presence of inflammatory infiltrates and neovascularization, not included in the score, were also studied. Correlation and chi-square tests were used to assess the association between histological variables and clinical or radiological variables. Interobserver agreement was also evaluated for the MRI variables using weighted kappa. No statistically significant correlation was found between histological variables (histological degeneration score, inflammatory infiltrates or neovascularization) and clinical or radiological variables. Interobserver agreement for radiological scores resulted in a kappa of 0.79 for the Pfirrmann scale and 0.65 for the Modic scale, both statistically significant. In our series of patients, we could not demonstrate any correlation between the degree of histological degeneration or the presence of inflammatory infiltrates when compared with radiological degeneration scales or clinical variables such as the patient's age or duration of symptoms. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

TEPAPA: a novel in silico feature learning pipeline for mining prognostic and associative factors from text-based electronic medical records.

PubMed

Lin, Frank Po-Yen; Pokorny, Adrian; Teng, Christina; Epstein, Richard J

2017-07-31

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder.

PubMed

Henje Blom, E; Olsson, E M; Serlachius, E; Ericson, M; Ingvar, M

2010-04-01

The aim of this study was to investigate heart rate variability (HRV) in a clinical sample of female adolescents with anxiety disorders (AD) and/or major depressive disorder (MDD) compared with healthy controls and to assess the effect of selective serotonin reuptake inhibitors (SSRI) on HRV. Heart rate variability was measured in adolescent female psychiatric patients with AD and/or MDD (n = 69), mean age 16.8 years (range: 14.5-18.4), from 13 out-patient clinics and in healthy controls (n = 65), mean age 16.5 years (range: 15.9-17.7). HRV was registered in the sitting position during 4 min with no interventions. Logarithmically transformed high frequency HRV (HF), low frequency HRV (LF) and standard deviation of inter beat intervals (SDNN) were lower in the clinical sample compared with the controls (Cohen's d for HF = 0.57, LF = 0.55, SDNN = 0.60). This was not explained by body mass index, blood pressure or physical activity. Medication with SSRI explained 15.5% of the total variance of HF, 3.0% of LF and 6.5% of SDNN. Adolescent female psychiatric patients with AD and/or MDD show reduced HRV compared with healthy controls. Medication with SSRI explained a part of this difference.

Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

PubMed Central

Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

2014-01-01

The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

Cardiac output and systemic vascular resistance: Clinical assessment compared with a noninvasive objective measurement in children with shock.

PubMed

Razavi, Asma; Newth, Christopher J L; Khemani, Robinder G; Beltramo, Fernando; Ross, Patrick A

2017-06-01

To evaluate physician assessment of cardiac output and systemic vascular resistance in patients with shock compared with an ultrasonic cardiac output monitor (USCOM). To explore potential changes in therapy decisions if USCOM data were available using physician intervention answers. Double-blinded, prospective, observational study in a tertiary hospital pediatric intensive care unit. Forty children (<18years) admitted with shock, requiring ongoing volume resuscitation or inotropic support. Two to 3 physicians clinically assessed cardiac output and systemic vascular resistance, categorizing them as high, normal, or low. An investigator simultaneously measured cardiac index (CI) and systemic vascular resistance index (SVRI) with USCOM categorized as high, normal, or low. Overall agreement between physician and USCOM for CI (48.5% [κ = 0.18]) and SVRI (45.9% [κ = 0.16]) was poor. Interobserver agreement was also poor for CI (58.7% [κ = 0.33]) and SVRI (52.3% [κ = 0.28]). Comparing theoretical physician interventions to "acceptable" or "unacceptable" clinical interventions, based on USCOM measurement, 56 (21%) physician interventions were found to be "unacceptable." There is poor agreement between physician-assessed CI and SVRI and USCOM, with significant interobserver variability among physicians. Objective measurement of CI and SVRI may reduce variability and improve diagnostic accuracy. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army.

PubMed

Patino, Luz H; Mendez, Claudia; Rodriguez, Omaira; Romero, Yanira; Velandia, Daniel; Alvarado, Maria; Pérez, Julie; Duque, Maria Clara; Ramírez, Juan David

2017-08-01

In Colombia, the cutaneous leishmaniasis (CL) is the most common manifestation across the army personnel. Hence, it is mandatory to determine the species associated with the disease as well as the association with the clinical traits. A total of 273 samples of male patients with CL were included in the study and clinical data of the patients was studied. PCR and sequencing analyses (Cytb and HSP70 genes) were performed to identify the species and the intra-specific genetic variability. A georeferenced database was constructed to identify the spatial distribution of Leishmania species isolated. The identification of five species of Leishmania that circulate in the areas where army personnel are deployed is described. Predominant infecting Leishmania species corresponds to L. braziliensis (61.1%), followed by Leishmania panamensis (33.5%), with a high distribution of both species at geographical and municipal level. The species L. guyanensis, L. mexicana and L. lainsoni were also detected at lower frequency. We also showed the identification of different genotypes within L. braziliensis and L. panamensis. In conclusion, we identified the Leishmania species circulating in the areas where Colombian army personnel are deployed, as well as the high intra-specific genetic variability of L. braziliensis and L. panamensis and how these genotypes are distributed at the geographic level.

Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis.

PubMed

Lewandowski, Kathryn E; Baker, Justin T; McCarthy, Julie M; Norris, Lesley A; Öngür, Dost

2018-04-01

Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery. Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report. A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings. We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2018, 24, 382-390).

Clinical and neurophysiological risk factors for falls in patients with bilateral vestibulopathy.

PubMed

Schniepp, Roman; Schlick, Cornelia; Schenkel, Fabian; Pradhan, Cauchy; Jahn, Klaus; Brandt, Thomas; Wuehr, Max

2017-02-01

Patients with bilateral vestibular failure (BVF) exhibit imbalance when standing and walking that is linked to a higher fall risk. The purpose of this study was to identify risk factors for falls in BVF. We therefore systematically investigated the interrelationship of clinical and demographic characteristics, gait impairments, and the fall frequency of these patients. Clinical and demographic characteristics as well as quantitative measures of gait performance on a pressure-sensitive gait carpet were collected from 55 patients with different etiologies of BVF. Clinical and demographic data as well as spatiotemporal gait characteristics were used for ANOVA testing and a logistic regression model with categorized fall events as dependent variables. The impairment of peripheral vestibular function, duration of disease, and the overall gait status were not associated with the history of falls in patients with BVF. In contrast, the most predictive factors for falls in BVF were an increase in temporal gait variability, especially at slow walking speeds (p < 0.001; OR = 1.3), and the presence of a concomitant peripheral neuropathy (p < 0.045; OR = 3.6). BVF patients with a high risk of falling exhibit specific gait alterations in a speed-dependent manner. In particular, increased gait fluctuations during slow walking are most predictive for an increased fall risk. The presence of a concomitant peripheral neuropathy further critically impairs postural stability in these patients. Clinical assessment of both these aspects is therefore important to identify those patients at a particularly high fall risk and to initiate preventive procedures early.

Comparison of electroacupuncture frequency-related effects on heart rate variability in healthy volunteers: a randomized clinical trial.

PubMed

Lee, Jong-Ho; Kim, Kyu-Hyeong; Hong, Jin-Woo; Lee, Won-Chul; Koo, Sungtae

2011-06-01

This study aimed to compare the effects of high frequency electroacupuncture (EA) and low-frequency EA on the autonomic nervous system by using a heart rate variability measuring device in normal individuals. Fourteen participants were recruited and each participated in the high-frequency and low-frequency sessions (crossover design). The order of sessions was randomized and the interval between the two sessions was over 2 weeks. Participants received needle insertion with 120-Hz stimulation during the high-frequency session (high-frequency EA group), and with 2-Hz stimulation during the low-frequency session (low-frequency EA group). Acupuncture needles were directly inserted perpendicularly to LI 4 and LI 11 acupoints followed by delivery of electric pulses to these points for 15 minutes. Heart rate variability was measured 5 minutes before and after EA stimulation by a heart rate variability measuring system. We found a significant increase in the standard deviation of the normal-to-normal interval in the high-frequency EA group, with no change in the low-frequency EA group. Both the high-frequency and low-frequency EA groups showed no significant differences in other parameters including high-frequency power, low-frequency power, and the ratio of low-frequency power to high-frequency power. Based on these findings, we concluded that high-frequency EA stimulation is more effective than low-frequency EA stimulation in increasing autonomic nervous activity and there is no difference between the two EA frequencies in enhancing sympathovagal balance. Copyright © 2011 Korean Pharmacopuncture Institute. Published by .. All rights reserved.

Rationale and Design of the Registry for Stones of the Kidney and Ureter (ReSKU): A Prospective Observational Registry to Study the Natural History of Urolithiasis Patients.

PubMed

Chang, Helena C; Tzou, David T; Usawachintachit, Manint; Duty, Brian D; Hsi, Ryan S; Harper, Jonathan D; Sorensen, Mathew D; Stoller, Marshall L; Sur, Roger L; Chi, Thomas

2016-12-01

Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database-the Registry for Stones of the Kidney and Ureter (ReSKU™)-was developed, and herein we describe our implementation outcomes. Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU. The number of variables within each instrument includes the following: New patient-60, Surgery-80, Postoperative-64, and Follow-up-64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient-12.06 ± 2.30, Postoperative-7.18 ± 1.02, and Follow-up-8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient-4.09 ± 1.73, Postoperative-1.41 ± 0.41, and Follow-up-0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated. ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease.

Rationale and Design of the Registry for Stones of the Kidney and Ureter (ReSKU): A Prospective Observational Registry to Study the Natural History of Urolithiasis Patients

PubMed Central

Chang, Helena C.; Tzou, David T.; Usawachintachit, Manint; Duty, Brian D.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Stoller, Marshall L.; Sur, Roger L.

2016-01-01

Abstract Objectives: Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database—the Registry for Stones of the Kidney and Ureter (ReSKU™)—was developed, and herein we describe our implementation outcomes. Materials and Methods: Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU. Results: The number of variables within each instrument includes the following: New patient—60, Surgery—80, Postoperative—64, and Follow-up—64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient—12.06 ± 2.30, Postoperative—7.18 ± 1.02, and Follow-up—8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient—4.09 ± 1.73, Postoperative—1.41 ± 0.41, and Follow-up—0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated. Conclusions: ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease. PMID:27758162

24-Hour Blood Pressure Variability Assessed by Average Real Variability: A Systematic Review and Meta-Analysis.

PubMed

Mena, Luis J; Felix, Vanessa G; Melgarejo, Jesus D; Maestre, Gladys E

2017-10-19

Although 24-hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24-hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24-hour BPV, including the average real variability (ARV) index. Studies chosen for review were those that presented data for 24-hour BPV in adults from meta-analysis, longitudinal or cross-sectional design, and examined BPV in terms of the following issues: (1) methods used to calculate and evaluate ARV; (2) assessment of 24-hour BPV determined using noninvasive ambulatory BP monitoring; (3) multivariate analysis adjusted for covariates, including some measure of BP; (4) association of 24-hour BPV with subclinical organ damage; and (5) the predictive value of 24-hour BPV on target organ damage and rate of cardiovascular events. Of the 19 assessed studies, 17 reported significant associations between high ARV and the presence and progression of subclinical organ damage, as well as the incidence of hard end points, such as cardiovascular events. In all these cases, ARV remained a significant independent predictor ( P <0.05) after adjustment for BP and other clinical factors. In addition, increased ARV in systolic BP was associated with risk of all cardiovascular events (hazard ratio, 1.18; 95% confidence interval, 1.09-1.27). Only 2 cross-sectional studies did not find that high ARV was a significant risk factor. Current evidence suggests that ARV index adds significant prognostic information to 24-hour ambulatory BP monitoring and is a useful approach for studying the clinical value of BPV. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Stroke patients' functions in personal activities of daily living in relation to sleep and socio-demographic and clinical variables in the acute phase after first-time stroke and at six months of follow-up.

PubMed

Bakken, Linda N; Kim, Hesook S; Finset, Arnstein; Lerdal, Anners

2012-07-01

To explore first-time stroke patients' degree of independence in activities of daily life in relation to sleep and other essential variables that might influence activities of daily life. Sleep has received little attention in rehabilitation of activities of daily life in stroke patients. This is a longitudinal survey and observational study design from the acute phase to six months poststroke. First-time stroke patients (n = 90) were recruited from two hospitals in eastern Norway in 2007 and 2008. Data were collected by survey interview, medical records and wrist actigraphy in the first two weeks at the hospital and at six months of follow-up. Actigraph measures patient activity and estimates sleep during the day and night. Linear regression showed that high dependence in personal activities of daily living was directly related to low estimated sleep time at night and higher estimated sleep during the day in the acute phase, controlling for socio-demographic and clinical variables. Furthermore, high estimated numbers of awakenings in the acute phase were related to lower activities of daily life functioning at six months of follow-up after controlling for socio-demographic and clinical variables. Stronger pain and a lower physical functioning showed direct relationships with lower independency level of in activities of daily life both in the acute phase and after six months. Sleep patterns in the acute phase may influence the patients' activities of daily life functioning up to six months poststroke. Furthermore, pain in the acute phase may influence the level of activities of daily life functioning in stroke patients. Nurses should pay attention to stroke patients' sleep quality and pain in the rehabilitation period after a stroke. Facilitating good sleep conditions and screening for pain should be an integral part of the rehabilitation programme. © 2012 Blackwell Publishing Ltd.

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

The association of clinical parameters and ultrasound verified inflammation with patients' and physicians' global assessments in psoriatic arthritis.

PubMed

Lackner, Angelika; Duftner, Christina; Ficjan, Anja; Gretler, Judith; Hermann, Josef; Husic, Rusmir; Graninger, Winfried B; Dejaco, Christian

2016-10-01

To study the association of clinical and/or ultrasound variables with patients' (PGA) and physicians' (EGA) global assessment of disease activity in psoriatic arthritis (PsA). The correlation of these parameters with the discordance between PGA and EGA, as well as with PGA/EGA changes over 6 months was also investigated. Prospective study of 83 consecutive PsA patients with 2 visits scheduled 6 months apart. All patients underwent the following assessments: tender (TJC) and swollen joint count (SJC), PASI, dactylitis and Leeds enthesitis index. PGA, patients' level of pain (pain VAS), EGA, and HAQ were also recorded. Grey scale (GS) and power Doppler (PD) ultrasound were performed at 68 joints (evaluating synovia and tendons) and 14 entheses. Regression analyses were performed to assess the association of these variables with PGA and EGA. Two new variables "PGAminusEGA" and "PGAchange - EGAchange" were developed to explore the discrepancy between PGA and EGA and the consistency of PGA/EGA changes over time, respectively. The parameters explaining most of PGA and EGA variability were pain VAS (30.5%) and SJC (48.5%), respectively. The correlation between EGA and joint counts was stronger in patients with high vs. low levels of ultrasound verified inflammation. PGAminusEGA was mainly explained by pain and SJC. Pain was the most important predictor of PGA change whereas TJC and HAQ were more closely associated with EGA changes. "PGAchange-EGAchange" was linked to pain and SJC. Ultrasound scores were not linked with either of these variables. Pain VAS and joint counts are the most important clinical parameters explaining patients' and physicians' perception of disease activity, whereas the correlation of active inflammation as verified by sonography with these factors is limited. Copyright © 2016 Elsevier Inc. All rights reserved.

When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

PubMed

Papadia, Andrea; Bellati, Filippo; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Donfrancesco, Cristina; Gasparri, Maria Luisa; Raspagliesi, Francesco

2015-12-01

The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

[Mother-newborn relational risk - Study of prevalence and associated variables].

PubMed

Muñoz, Maribel; Poo, Ana María; Baeza, Bernardita; Bustos, M Luis

2015-01-01

Clinical evidence reveals the importance of mother-newborn bonding experience for health promoting and maintenance of human life. If the newborn lacks care and affection, she/he may develop an attachment disorder. A predictive scale regarding the risk of mothernewborn relationships is available, which makes possible an early intervention to prevent the development of relational disorders. The aim of this study is to apply the Kimelman measurement scale to determine the relational risk in mother-newborn pairs, as well as the prevalence and the associated biopsychosocial variables. A cross-sectional study with a probabilistic sample of 333 mother-infant pairs in postpartum maternity at Temuco hospital. The Kimelman mother-newborn attachment assessment guide was used. Biopsychosocial variables were obtained from the mothers studied. The association of biopsychosocial variables with relational risk was analyzed using OR and confidence intervals of 95%. The prevalence of high relational risk was 43.8%. The associated biopsychosocial variables included, women with no steady partner, single parent, teenage mothers, unwanted and unplanned pregnancy. Almost half of the mothers were in the high risk group. Early identification of relational risk and its related variables could help in the intervention in this vulnerable group. Copyright © 2015. Publicado por Elsevier España, S.L.U.

[Total knee and hip prosthesis: variables associated with costs].

PubMed

Herrera-Espiñeira, Carmen; Escobar, Antonio; Navarro-Espigares, José Luis; Castillo, Juan de Dios Lunadel; García-Pérez, Lidia; Godoy-Montijano, Amparo

2013-01-01

The elevated prevalence of osteoarthritis in Western countries, the high costs of hip and knee arthroplasty, and the wide variations in the clinical practice have generated considerable interest in comparing the associated costs before and after surgery. To determine the influence of a number of variables on the costs of total knee and hip arthroplasty surgery during the hospital stay and during the one-year post-discharge. A prospective multi-center study was performed in 15 hospitals from three Spanish regions. Relationships between the independent variables and the costs of hospital stay and postdischarge follow-up were analyzed by using multilevel models in which the "hospital" variable was used to group cases. Independent variables were: age, sex, body mass index, preoperative quality of life (SF-12, EQ-5 and Womac questionnaires), surgery (hip/knee), Charlson Index, general and local complications, number of beds and economic-institutional dependency of the hospital, the autonomous region to which it belongs, and the presence of a caregiver. The cost of hospital stay, excluding the cost of the prosthesis, was 4,734 Euros, and the post-discharge cost was 554 Euros. With regard to hospital stay costs, the variance among hospitals explained 44-46% of the total variance among the patients. With regard to the post-discharge costs, the variability among hospitals explained 7-9% of the variance among the patients. There is considerable potential for reducing the hospital stay costs of these patients, given that more than 44% of the observed variability was not determined by the clinical conditions of the patients but rather by the behavior of the hospitals.

Analytical variability of estimated platelet counts on canine blood smears.

PubMed

Paltrinieri, Saverio; Paciletti, Veronica; Zambarbieri, Jari

2018-06-04

The analytical variability of estimated platelet counts in dogs has not been reported. The purpose of this study was to assess the magnitude of analytical imprecision of platelet estimates and the possible impact of this imprecision on clinical decisions. Three independent observers counted the number of platelets in 3 different areas (LE = lateral edge; CM = central monolayer; FE = feathered edge) of 30 canine blood smears with different instrumental platelet counts. The coefficient of variation (CV) for each observer was calculated in different areas of each smear (intra-observer variability), among different regions of each smear (inter-area variability), and among different observers in each area (inter-observer variability). The influence of these variabilities on the classification of platelet estimates as adequate, increased, or decreased was also assessed. The CVs recorded in the different areas by each observer ranged from 8% to 88% and were negatively correlated (P < .001, r = -.65) with the mean number of platelets per field. The mean platelet number was significantly lower in the FE and significantly higher in the CM compared with the LE, but the magnitude of this difference varied with the operators. The concordance among operators regarding platelet estimates was fair (k = 0.36) to substantial (k = 0.71) depending on the area. The overall inter-area concordance was moderate (k = 0.59). Platelet estimates suffer from high variability that could lead to patient misclassification. Therefore, guidelines to standardize the platelet estimate are needed. © 2018 American Society for Veterinary Clinical Pathology.

[Modeling the academic performance of medical students in basic sciences and pre-clinical courses: a longitudinal study].

PubMed

Zúñiga, Denisse; Mena, Beltrán; Oliva, Rose; Pedrals, Nuria; Padilla, Oslando; Bitran, Marcela

2009-10-01

The study of predictors of academic performance is relevant for medical education. Most studies of academic performance use global ratings as outcome measure, and do not evaluate the influence of the assessment methods. To model by multivariate analysis, the academic performance of medical considering, besides academic and demographic variables, the methods used to assess students' learning and their preferred modes of information processing. Two hundred seventy two students admitted to the medical school of the Pontificia Universidad Católica de Chile from 2000 to 2003. Six groups of variables were studied to model the students' performance in five basic science courses (Anatomy, Biology, Calculus, Chemistry and Physics) and two pre-clinical courses (Integrated Medical Clinic I and IT). The assessment methods examined were multiple choice question tests, Objective Structured Clinical Examination and tutor appraisal. The results of the university admission tests (high school grades, mathematics and biology tests), the assessment methods used, the curricular year and previous application to medical school, were predictors of academic performance. The information processing modes influenced academic performance, but only in interaction with other variables. Perception (abstract or concrete) interacted with the assessment methods, and information use (active or reflexive), with sex. The correlation between the real and predicted grades was 0.7. In addition to the academic results obtained prior to university entrance, the methods of assessment used in the university and the information processing modes influence the academic performance of medical students in basic and preclinical courses.

Effectiveness outcomes in attention-deficit/hyperactivity disorder.

PubMed

Weiss, Margaret D; Gadow, Kenneth; Wasdell, Michael B

2006-01-01

Attention-deficit/hyperactivity disorder (ADHD) is common, chronic, and associated with significant functional impairment. It is highly treatable. It is therefore not only a major public health problem but also one that provides a unique opportunity in medicine to make a significant difference. This article will discuss the methodology needed to demonstrate empirically the impact of treatment on actual burden of illness in practice. Where efficacy studies demonstrate whether a treatment can work, effectiveness studies tell us whether they actually do work. Clinical trials exclude incompetent, non-compliant, and seriously comorbid patients, so that the information obtained from these trials tells us the most about the patients we see the least. Small differences in effect size in pivotal trials of efficacy have become a key variable for rating treatments as first line or second line, without consideration of effectiveness variables such as comorbidity, difficulty with appetite or sleep, patient preference, capacity for compliance, timing of functional impairment, and substance use. These effectiveness variables are less well studied, but critical to clinical decision making. In reality, fewer than 10% of our patients comply with and persist with treatment. To learn more about why patients are discontinuing treatment, we need to explore measures of effectiveness empirically. Effectiveness studies are also important to provide regulatory bodies with the data they need to balance the risk of treatment with the risk of failing to treat. Practical clinical trials and naturalistic follow-up studies will allow us to evaluate the true clinical impact of short-term efficacy trials.

PERFORMANCE OF HIGH SCHOOL FOOTBALL PLAYERS ON CLINICAL MEASURES OF DEEP CERVICAL FLEXOR ENDURANCE AND CERVICAL ACTIVE RANGE OF MOTION: IS HISTORY OF CONCUSSION A FACTOR?

PubMed Central

Ruediger, Thomas; Alsalaheen, Bara; Bean, Ryan

2016-01-01

Background More than one million adolescent athletes participated in organized high school sanctioned football during the 2014-15 season. These athletes are at risk for sustaining concussion. Although cervical spine active range of motion (AROM) and deep neck flexor endurance may serve a preventative role in concussion, and widespread clinical use of measurements of these variables, reference values are not available for this population. Cost effective, clinically relevant methods for measuring neck endurance are also well established for adolescent athletes. Purpose The purpose of this study was to report reference values for deep cervical flexor endurance and cervical AROM in adolescent football players and examine whether differences in these measures exist in high school football players with and without a history of concussion. Methods Concussion history, cervical AROM, and deep neck flexor endurance were measured in 122 high school football players. Reference values were calculated for AROM and endurance measures; association were examined between various descriptive variables and concussion. Results No statistically significant differences were found between athletes with a history of concussion and those without. A modest inverse correlation was seen between body mass and AROM in the sagittal and transverse planes. Conclusion The results of this study indicate that the participants with larger body mass had less cervical AROM in some directions. While cervical AROM and endurance measurements may not be adequate to identify adolescents with a history of previous concussions among high school football players. However, if a concussion is sustained, these measures can offer a baseline to examine whether cervical AROM is affected as compared to healthy adolescents. Level of Evidence 2c PMID:27104049

Spatial variability in the pollen count in Sydney, Australia: can one sampling site accurately reflect the pollen count for a region?

PubMed

Katelaris, Constance H; Burke, Therese V; Byth, Karen

2004-08-01

There is increasing interest in the daily pollen count, with pollen-sensitive individuals using it to determine medication use and researchers relying on it for commencing clinical drug trials and assessing drug efficacy according to allergen exposure. Counts are often expressed qualitatively as low, medium, and high, and often only 1 pollen trap is used for an entire region. To examine the spatial variability in the pollen count in Sydney, Australia, and to compare discrepancies among low-, medium-, and high-count days at 3 sites separated by a maximum of 30 km. Three sites in western Sydney were sampled using Burkard traps. Data from the 3 sites were used to compare vegetation differences, possible effects of some meteorological parameters, and discrepancies among sites in low-, medium-, and high-count days. Total pollen counts during the spring months were 14,382 grains/m3 at Homebush, 11,584 grains/m3 at Eastern Creek, and 9,269 grains/m3 at Nepean. The only significant correlation between differences in meteorological parameters and differences in pollen counts was the Homebush-Nepean differences in rainfall and pollen counts. Comparison between low- and high-count days among the 3 sites revealed a discordance rate of 8% to 17%. For informing the public about pollen counts, the count from 1 trap is a reasonable estimation in a 30-km region; however, the discrepancies among 3 trap sites would have a significant impact on the performance of a clinical trial where enrollment was determined by a low or high count. Therefore, for clinical studies, data collection must be local and applicable to the study population.

PERFORMANCE OF HIGH SCHOOL FOOTBALL PLAYERS ON CLINICAL MEASURES OF DEEP CERVICAL FLEXOR ENDURANCE AND CERVICAL ACTIVE RANGE OF MOTION: IS HISTORY OF CONCUSSION A FACTOR?

PubMed

Smith, Laura; Ruediger, Thomas; Alsalaheen, Bara; Bean, Ryan

2016-04-01

More than one million adolescent athletes participated in organized high school sanctioned football during the 2014-15 season. These athletes are at risk for sustaining concussion. Although cervical spine active range of motion (AROM) and deep neck flexor endurance may serve a preventative role in concussion, and widespread clinical use of measurements of these variables, reference values are not available for this population. Cost effective, clinically relevant methods for measuring neck endurance are also well established for adolescent athletes. The purpose of this study was to report reference values for deep cervical flexor endurance and cervical AROM in adolescent football players and examine whether differences in these measures exist in high school football players with and without a history of concussion. Concussion history, cervical AROM, and deep neck flexor endurance were measured in 122 high school football players. Reference values were calculated for AROM and endurance measures; association were examined between various descriptive variables and concussion. No statistically significant differences were found between athletes with a history of concussion and those without. A modest inverse correlation was seen between body mass and AROM in the sagittal and transverse planes. The results of this study indicate that the participants with larger body mass had less cervical AROM in some directions. While cervical AROM and endurance measurements may not be adequate to identify adolescents with a history of previous concussions among high school football players. However, if a concussion is sustained, these measures can offer a baseline to examine whether cervical AROM is affected as compared to healthy adolescents. 2c.

Perceived Causal Relations: Novel Methodology for Assessing Client Attributions about Causal Associations between Variables Including Symptoms and Functional Impairment

ERIC Educational Resources Information Center

Frewen, Paul A.; Allen, Samantha L.; Lanius, Ruth A.; Neufeld, Richard W. J.

2012-01-01

Researchers have argued that the investigation of causal interrelationships between symptoms may help explain the high comorbidity rate between certain psychiatric disorders. Clients' own attributions concerning the causal interrelationships linking the co-occurrence of their symptoms represent data that may inform their clinical case…

Brief Report: Discrimination of Foreign Speech Pitch and Autistic Traits in Non-Clinical Population

ERIC Educational Resources Information Center

Iao, Lai-Sang; Wippich, Anna; Lam, Yu Hin

2018-01-01

Individuals with Autism Spectrum Conditions (ASC) are widely suggested to show enhanced perceptual discrimination but inconsistent findings have been reported for pitch discrimination. Given the high variability in ASC, this study investigated whether ASC traits were correlated with pitch discrimination in an undergraduate sample when musical and…

Risk factors for fatigue in patients with epilepsy.

PubMed

Yan, Song; Wu, Yuanbin; Deng, Yanchun; Liu, Yonghong; Zhao, Jingjing; Ma, Lei

2016-11-01

Fatigue is highly prevalent in patients with epilepsy and has a major impact on quality of life, but little data is available on its effects and management in epilepsy. To identify the incidence and risk factors of fatigue in patients with epilepsy, 105 epilepsy patients (45 women and 60 men) were enrolled in our study. Demographic and clinical data were collected and psychological variables including fatigue, sleep quality, excess daytime sleepiness, anxiety, and depression were measured by Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale, respectively. Of 105 patients, 29.5% exhibited fatigue (FSS score ⩾4). We found no correlation between the occurrence of fatigue and any of our demographic or clinical variables. Fatigue is correlated with low sleep quality, anxiety, and depression, but not with excess daytime sleepiness. Thus, we concluded that fatigue is highly prevalent in patients with epilepsy, and that low sleep quality, anxiety, and depression are significantly correlated with fatigue in epileptics, while excess daytime sleepiness not. Copyright © 2016. Published by Elsevier Ltd.

Past Tense Marking by African American English–Speaking Children Reared in Poverty

PubMed Central

Pruitt, Sonja; Oetting, Janna

2012-01-01

Purpose This study examined past tense marking by African American English (AAE)-speaking children from low- and middle-income backgrounds to determine if poverty affects children’s marking of past tense in ways that mirror the clinical condition of specific language impairment (SLI). Method Participants were 15 AAE-speaking 6-year-olds from low-income backgrounds, 15 AAE-speaking 6-year-olds from middle-income backgrounds who served as age-matched controls, and 15 AAE-speaking 5-year-olds from middle-income backgrounds who served as language-matched controls. Data were drawn from language samples and probes. Results Results revealed high rates of regular marking, variable rates of irregular marking, high rates of over-regularizations, and absence of dialect-inappropriate errors of commission. For some analyses, marking was affected by the phonological characteristics of the items and the children’s ages, but none of the analyses revealed effects for the children’s socioeconomic level. Conclusions Within AAE, poverty status as a variable affects past tense marking in ways that are different from the clinical condition of SLI. PMID:18695014

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

PubMed

Choi, Hongyoon; Ha, Seunggyun; Im, Hyung Jun; Paek, Sun Ha; Lee, Dong Soo

2017-01-01

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

[Big data in imaging].

PubMed

Sewerin, Philipp; Ostendorf, Benedikt; Hueber, Axel J; Kleyer, Arnd

2018-04-01

Until now, most major medical advancements have been achieved through hypothesis-driven research within the scope of clinical trials. However, due to a multitude of variables, only a certain number of research questions could be addressed during a single study, thus rendering these studies expensive and time consuming. Big data acquisition enables a new data-based approach in which large volumes of data can be used to investigate all variables, thus opening new horizons. Due to universal digitalization of the data as well as ever-improving hard- and software solutions, imaging would appear to be predestined for such analyses. Several small studies have already demonstrated that automated analysis algorithms and artificial intelligence can identify pathologies with high precision. Such automated systems would also seem well suited for rheumatology imaging, since a method for individualized risk stratification has long been sought for these patients. However, despite all the promising options, the heterogeneity of the data and highly complex regulations covering data protection in Germany would still render a big data solution for imaging difficult today. Overcoming these boundaries is challenging, but the enormous potential advances in clinical management and science render pursuit of this goal worthwhile.

Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.

PubMed

Mantovani, Giovanni; Madeddu, Clelia; Macciò, Antonio; Gramignano, Giulia; Lusso, Maria Rita; Massa, Elena; Astara, Giorgio; Serpe, Roberto

2004-10-01

Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment. The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).

[Glycemic variability and oxidative stress in children, with type 1 diabetes attending a summer camp].

PubMed

Colomo, N; Tapia, M J; Vallejo, M R; García-Torres, F; Rubio-Martín, E; Caballero, F F; Jiménez, J M; Pelaez, M J; Gómez, A M; Sánchez, I; López-Siguero, J P; Soriguer, F; Ruiz de Adana, M S

2014-09-01

To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp. Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children. The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α. High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Risk Prediction Models for Acute Kidney Injury in Critically Ill Patients: Opus in Progressu.

PubMed

Neyra, Javier A; Leaf, David E

2018-05-31

Acute kidney injury (AKI) is a complex systemic syndrome associated with high morbidity and mortality. Among critically ill patients admitted to intensive care units (ICUs), the incidence of AKI is as high as 50% and is associated with dismal outcomes. Thus, the development and validation of clinical risk prediction tools that accurately identify patients at high risk for AKI in the ICU is of paramount importance. We provide a comprehensive review of 3 clinical risk prediction tools that have been developed for incident AKI occurring in the first few hours or days following admission to the ICU. We found substantial heterogeneity among the clinical variables that were examined and included as significant predictors of AKI in the final models. The area under the receiver operating characteristic curves was ∼0.8 for all 3 models, indicating satisfactory model performance, though positive predictive values ranged from only 23 to 38%. Hence, further research is needed to develop more accurate and reproducible clinical risk prediction tools. Strategies for improved assessment of AKI susceptibility in the ICU include the incorporation of dynamic (time-varying) clinical parameters, as well as biomarker, functional, imaging, and genomic data. © 2018 S. Karger AG, Basel.

Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation.

PubMed

Lesche, Dorothea; Sigurdardottir, Vilborg; Setoud, Raschid; Englberger, Lars; Fiedler, Georg M; Largiadèr, Carlo R; Mohacsi, Paul; Sistonen, Johanna

2015-12-01

Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped, and clinical data were retrieved from patient charts. While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (p = 0.031). ERL dose requirement was 0.02 mg/kg/d higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (p = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 mL/min/1.73 m(2)) in patients with baseline kidney dysfunction. Everolimus pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence and associated risk factors of latent tuberculosis infection in a Spanish prison.

PubMed

López de Goicoechea-Saiz, M E; Sternberg, F; Portilla-Sogorb, J

2018-01-01

To determine the prevalence of latent tuberculosis infection (LTI) in a Spanish prison, analyze the main sociodemographic and clinical variables associated with this condition and estimate the percentage of individuals with LTI who have received chemoprophylactic treatment. Cross-sectional study including inmates hosted in the Madrid VI Prison on 16/07/2016. Exclusion criteria: history of tuberculosis; non-updated tuberculin test according to the Tuberculosis Prevention and Control Program in Prisons protocol. Information of the variables was collected from SANIT and SIP programs, and by checking the clinical records of inmates. Description of the participant population and comparison between the frequency of distribution of the independent variables in LTI present and absent groups were performed, the last calculating the p value with Ji2 and Mann-Whitney U tests. Bivariate and multivariate analysis have been carried out with a logistic regression model. 936 individuals have been included. The prevalence of LTI in prison is 54.6%. This condition has been linked to the sociodemographic variables age, sex and nationality of origin, being age the one that has shown the strongest association. Among the other factors analyzed, only HCV infection behaves as a predictor of LTI. 30.3% of the individuals with LTI have completed or are receiving chemoprophylactic treatment in the moment of the study. LTI prevalence is high in the Spanish current prison population. The results of the study emphasize the relevance of the LTI screening in the prison setting, specially among high risk groups, and point out the need of a greater effort in the indication and completion of the chemoprophylactic treatment.

The influence of cultural variables on treatment retention and engagement in a sample of Mexican American adolescent males with substance use disorders.

PubMed

Burrow-Sánchez, Jason J; Meyers, Kimberly; Corrales, Carolina; Ortiz-Jensen, Cynthia

2015-12-01

Adolescent substance abuse is a serious public health concern, and in response to this problem, a number of effective treatment approaches have been developed. Despite this, retaining and engaging adolescents in treatment are 2 major challenges continuously faced by practitioners and clinical researchers. Low retention and engagement rates are especially salient for ethnic minority adolescents because they are at high risk for underutilization of substance abuse treatment compared to their White peers. Latino adolescents, in particular, are part of the fastest growing ethnic minority group in the United States and experience high rates of substance use disorders. Heretofore, the empirical examination of cultural factors that influence treatment retention and engagement has been lacking in the literature. The goal of this study was to investigate the influence of the cultural variables ethnic identity, familism, and acculturation on the retention and engagement of Latino adolescents participating in substance abuse treatment. This study used data collected from a sample of Latino adolescent males (N = 96), predominantly of Mexican descent, and largely recruited from the juvenile justice system. Analysis was conducted using generalized regression models for count variables. Results indicated that higher levels of exploration, a subfactor of ethnic identity, and familism were predictive of attendance and engagement. In contrast, higher levels of Anglo orientation, a subfactor of acculturation, were predictive of lower treatment attendance and engagement. Clinical implications for the variables of ethnic identity, acculturation, and familism as well as suggestions for future research are discussed. (c) 2016 APA, all rights reserved).

Phenotypic variability in monozygotic twins with neurofibromatosis 2

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

Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affectedmore » organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.« less

Attention-deficit/hyperactivity disorder and phonological working memory: Methodological variability affects clinical and experimental performance metrics.

PubMed

Tarle, Stephanie J; Alderson, R Matt; Patros, Connor H G; Lea, Sarah E; Hudec, Kristen L; Arrington, Elaine F

2017-05-01

Despite promising findings in extant research that suggest impaired working memory (WM) serves as a central neurocognitive deficit or candidate endophenotype of attention-deficit/hyperactivity disorder (ADHD), findings from translational research have been relatively underwhelming. This study aimed to explicate previous equivocal findings by systematically examining the effect of methodological variability on WM performance estimates across experimental and clinical WM measures. Age-matched boys (ages 8-12 years) with (n = 20) and without (n = 20) ADHD completed 1 experimental (phonological) and 2 clinical (digit span, letter-number sequencing) WM measures. The use of partial scoring procedures, administration of greater trial numbers, and high central executive demands yielded moderate-to-large between-groups effect sizes. Moreover, the combination of these best-case procedures, compared to worst-case procedures (i.e., absolute scoring, administration of few trials, use of discontinue rules, and low central executive demands), resulted in a 12.5% increase in correct group classification. Collectively, these findings explain inconsistent ADHD-related WM deficits in previous reports, and highlight the need for revised clinical measures that utilize best-case procedures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Epidemiological, clinical, microbiological and therapeutic differences in tuberculosis disease in patients with and without HIV infection.

PubMed

Martínez-Sanz, Javier; Lago-Gómez, María Rosa; Rodríguez-Zurita, María Elena; Martín-Echevarría, Esteban; Torralba, Miguel

2018-04-23

Our objective is to analyze the incidence of tuberculosis (TB) in our population and to compare the characteristics of patients with and without HIV infection. Clinical-epidemiological retrospective cohort study that included patients diagnosed with TB with and without HIV infection between 2005-2016 in the province of Guadalajara (Spain). Epidemiological, clinical, microbiological and therapeutic variables were assessed, including microbiological resistances. TB was diagnosed in 261 patients. There were 25 patients (9.6%) who had HIV infection. Patients with HIV infection were predominantly males, had higher incidence of hepatitis C virus, a higher percentage of extrapulmonary TB, a higher prevalence of resistance to isoniazid and rifampicin, a greater paradoxical response and a longer average hospital stay. On the other hand, they had a lower percentage of positive tuberculin skin test and positive sputum smear (microscopy). A significant percentage of TB patients had no serology for HIV. Patients with HIV infection show remarkable differences in epidemiological, clinical and resistance variables to antituberculosis drugs. A high percentage of patients with TB were not tested for HIV. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Clinical spectrum of anorexia nervosa in children.

PubMed

Atkins, D M; Silber, T J

1993-08-01

A retrospective review of 21 patients ages 12 years and younger (age of onset range 7 to 12 years) with anorexia nervosa showed diagnostic delay in the youngest ones, high incidence of family psychiatric history, a remarkable severity of illness, and positive response to intensive treatment. Additional findings included significant comorbidity, a distinct subgroup with personality disorder and another with features of the "vulnerable child syndrome." This broad clinical spectrum of anorexia nervosa in children may explain the great variability in outcome. The development of anorexia nervosa in children relates to a complex combination of etiological and trigger factors. Precipitants identified in this study were physical maturation, entry into junior high, loss, or some combination thereof.

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

PubMed Central

Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

2012-01-01

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics

PubMed Central

Tyan, Marina; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-01-01

Background Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients’ facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. Objective The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. Methods All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. Results The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. Conclusions In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. PMID:29109068

Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer.

PubMed

Wang, Ming-yi; Chen, Cheng; Gao, Xiao-zhong; Li, Jie; Yue, Jing; Ling, Feng; Wang, Xiao-chun; Shao, Shi-he

2013-01-01

Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p < 0.001). The most prevalent vacA genotypes were s1a/m2 (48.3%) and s1c/m2 (13.8%). Thirty-six strains (31.0%) possessed dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

What variables can influence clinical reasoning?

PubMed Central

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-01-01

Background: Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Materials and Methods: Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. Results: There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R2 chnage = 0.46, P Value = 0.000). Conclusion: Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction. PMID:23853636

Second-look arthroscopic findings after open-wedge high tibia osteotomy focusing on the posterior root tears of the medial meniscus.

PubMed

Nha, Kyung-Wook; Lee, Yong Seuk; Hwang, Dae-Hee; Kwon, Jae Ho; Chae, Dong Ju; Park, Young Jee; Kim, Jong In

2013-02-01

This study examined, at second-look arthroscopy, the results of open-wedge high tibial osteotomy (HTO) focusing on root tear of the medial meniscus posterior horn (RTMMP). Among 31 consecutive patients who underwent HTO without a meniscectomy or pullout repair for RTMMP, 20 patients were available for second-look arthroscopic evaluation. All patients had medial unicompartmental arthritis. The healing status of the RTMMP was classified as complete, incomplete, and no healing. The difference in the weight bearing line from presurgery to the last follow-up was evaluated. Osteoarthritis and chondral lesions were evaluated, as were clinical results. Correlations between healing status and other variables (weight bearing line, cartilage status, and clinical scores) were assessed. The healed (10 patients) and nonhealed (incomplete 6 patients + no healing 4 patients) groups were also evaluated with respect to other variables. There were 10 (50%) cases with complete healing, 6 (30%) with incomplete healing, and 4 (20%) with no healing. Kellgren-Lawrence grade did not improve according to the standing plain radiograph (P = .09). Progression of chondral lesions was not observed at second-look arthroscopy; some improvement was even observed (P = .002). The median Lysholm score improved from 58 preoperatively to 88.5 at the last follow-up. The median Hospital for Special Surgery (HSS) score also increased significantly from 62.4 (range, 50 to 76) to 87.2 (range, 80 to 92; P = .003). The comparison between healed and nonhealed groups revealed no statistical differences in all variables. This study revealed a high rate of healing of RTMMP after HTO without attempted repair. Healing of the meniscus was not associated with an improved clinical outcome. Level IV, therapeutic case series. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

PubMed

Timmer, Margriet R; Martinez, Pierre; Lau, Chiu T; Westra, Wytske M; Calpe, Silvia; Rygiel, Agnieszka M; Rosmolen, Wilda D; Meijer, Sybren L; Ten Kate, Fiebo J W; Dijkgraaf, Marcel G W; Mallant-Hent, Rosalie C; Naber, Anton H J; van Oijen, Arnoud H A M; Baak, Lubbertus C; Scholten, Pieter; Böhmer, Clarisse J M; Fockens, Paul; Maley, Carlo C; Graham, Trevor A; Bergman, Jacques J G H M; Krishnadath, Kausilia K

2016-10-01

The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. 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/

Gene Expression Signatures Based on Variability can Robustly Predict Tumor Progression and Prognosis

PubMed Central

Dinalankara, Wikum; Bravo, Héctor Corrada

2015-01-01

Gene expression signatures are commonly used to create cancer prognosis and diagnosis methods, yet only a small number of them are successfully deployed in the clinic since many fail to replicate performance on subsequent validation. A primary reason for this lack of reproducibility is the fact that these signatures attempt to model the highly variable and unstable genomic behavior of cancer. Our group recently introduced gene expression anti-profiles as a robust methodology to derive gene expression signatures based on the observation that while gene expression measurements are highly heterogeneous across tumors of a specific cancer type relative to the normal tissue, their degree of deviation from normal tissue expression in specific genes involved in tissue differentiation is a stable tumor mark that is reproducible across experiments and cancer types. Here we show that constructing gene expression signatures based on variability and the anti-profile approach yields classifiers capable of successfully distinguishing benign growths from cancerous growths based on deviation from normal expression. We then show that this same approach generates stable and reproducible signatures that predict probability of relapse and survival based on tumor gene expression. These results suggest that using the anti-profile framework for the discovery of genomic signatures is an avenue leading to the development of reproducible signatures suitable for adoption in clinical settings. PMID:26078586

Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review.

PubMed

Basmaci, Romain; Vazouras, Konstantinos; Bielicki, Julia; Folgori, Laura; Hsia, Yingfen; Zaoutis, Theoklis; Sharland, Mike

2017-12-01

Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist. To assess the criteria used for patient selection and the efficacy end points in febrile pediatric UTI CTs. Medline, Embase, Cochrane central databases, and clinicaltrials.gov were searched between January 1, 1990, and November 24, 2016. We combined Medical Subject Headings terms and free-text terms for "urinary tract infections" and "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086 articles. Two independent reviewers assessed study quality and performed data extraction. We included 40 CTs in which a total of 4381 cases of pediatric UTIs were investigated. Positive urine culture results and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria, and colony thresholds were highly variable. Clinical and microbiological end points were assessed in 88% and 93% of the studies, respectively. Timing for end point assessment was highly variable, and only 3 studies (17%) out of the 18 performed after the Food and Drug Administration 1998 guidance publication assessed primary and secondary end points consistently with this guidance. Our limitations included a mixed population of healthy children and children with an underlying condition. In 6 trials, researchers studied a subgroup of patients with afebrile UTI. We observed a wide variability in the microbiological inclusion criteria and the timing for end point assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is necessary. Copyright © 2017 by the American Academy of Pediatrics.

Time trends in antithrombotic management of patients with atrial fibrillation treated with coronary stents: Results from TALENT-AF (The internAtionaL stENT - Atrial Fibrillation study) multicenter registry.

PubMed

Potter, Brian J; Andò, Giuseppe; Cimmino, Giovanni; Ladeiras-Lopes, Ricardo; Frikah, Zied; Chen, Xin Yue; Virga, Vittorio; Goncalves-Almeida, Joao; Camm, A John; Fox, Keith A A

2018-04-01

Antithrombotic management of patients with atrial fibrillation (AF) requiring percutaneous coronary intervention (PCI) is highly variable; limited evidence-based guidelines exist to influence practice. Patient characteristics and availability of novel drugs may have contributed to practice variability. We undertook an international multicenter retrospective registry of AF patients treated with PCI. The primary measures of interest were antiplatelet and OAC prescriptions at discharge. We compared temporal trends between Prior (2010-2012) and Recent (2013-2015) cohorts and investigated variables associated with OAC prescription. We identified 488 cases (140 Prior, 348 Recent). Median CHADS 2 and HAS-BLED scores were 2 (IQR, 1-3) and 2 (IQR, 2-3). Clinical characteristics were similar between cohorts, with high (85%) prevalence of ACS. More patients in the Recent cohort, compared with Prior, received OAC (56.9% vs 44.3%; P = 0.01) and NOAC (27.3% vs 3.6%; P < 0.01) at baseline. Triple therapy at discharge was not different between the cohorts. Clinical presentation with ACS and consequent use of potent P2Y 12 inhibitors were associated with reduced odds of OAC prescription at discharge (OR: 0.57, P = 0.045 and OR: 0.38, P = 0.023, respectively). Despite little change over time in clinical characteristics of AF patients undergoing PCI, significantly more patients received OAC at presentation. However, triple therapy was not more frequent in the Recent cohort, and ACS presentation was associated with lack of OAC at discharge. We underscore the need for trial evidence and use of updated guidelines to assist clinicians in balancing ischemic and bleeding risks. © 2018 Wiley Periodicals, Inc.

The real world cost and health resource utilization associated to manic episodes: The MANACOR study.

PubMed

Hidalgo-Mazzei, Diego; Undurraga, Juan; Reinares, María; Bonnín, Caterina del Mar; Sáez, Cristina; Mur, María; Nieto, Evaristo; Vieta, Eduard

2015-01-01

Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Relationships between pediatric asthma and socioeconomic/urban variables in Baltimore, Maryland

NASA Technical Reports Server (NTRS)

Kimes, Daniel; Ullah, Asad; Levine, Elissa; Nelson, Ross; Timmins, Sidey; Weiss, Sheila; Bollinger, Mary E.; Blaisdell, Carol

2004-01-01

Spatial relationships between clinical data for pediatric asthmatics (hospital and emergency department utilization rates), and socioeconomic and urban characteristics in Baltimore City were analyzed with the aim of identifying factors that contribute to increased asthma rates. Socioeconomic variables and urban characteristics derived from satellite data explained 95% of the spatial variation in hospital rates. The proportion of families headed by a single female was the most important variable accounting for 89% of the spatial variation. Evidence suggests that the high rates of hospital admissions and emergency department (ED) visits may partially be due to the difficulty of single parents with limited resources managing their child's asthma condition properly. This knowledge can be used for education towards mitigating ED and hospital events in Baltimore City.

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

PubMed Central

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-01-01

Objectives Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. Setting The setting for this research was a major academic institution in Beijing, China. Participants The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Methods Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Results Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. Conclusion These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. PMID:28928184

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study.

PubMed

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-09-18

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. The setting for this research was a major academic institution in Beijing, China. The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Relationship between reflection ability and clinical performance: a cross-sectional and retrospective-longitudinal correlational cohort study in midwifery.

PubMed

Embo, M; Driessen, E; Valcke, M; van der Vleuten, C P M

2015-01-01

increasingly, reflection is highlighted as integral to core practice competencies but empirical research into the relationship between reflection and performance in the clinical workplace is scarce. this study investigated the relationship between reflection ability and clinical performance. we designed a cross-sectional and a retrospective-longitudinal cohort study. Data from first, second and third year midwifery students were collected to study the variables 'clinical performance' and 'reflection ability'. Data were analysed with SPSS for Windows, Release 20.0. Descriptive statistics, Pearson׳s Product Moment Correlation Coefficients (r) and r² values were computed to investigate associations between the research variables. the results showed a moderate observed correlation between reflection ability and clinical performance scores. When adopting a cross-sectional perspective, all correlation values were significant (p<0.01) and above 0.4, with the exception of the third year correlations. Assuming perfect reliability in the measurement, the adjusted correlations, for year 2 and year 3 indicated a high association between reflection ability and clinical performance (>0.6). The results based on the retrospective-longitudinal data set explained a moderate proportion of the variance after correction for attenuation. Finally, the results indicate that 'reflection ability' scores of earlier years are significant related with 'clinical performance' scores of subsequent years. These results suggest that (1) reflection ability is linked to clinical performance; (2) that written reflections are an important, but not the sole way to assess professional competence and that (3) reflection is a contributor to clinical performance improvement. the data showed a moderate but significant relationship between 'reflection ability' and 'clinical performance' scores in clinical practice of midwifery students. Reflection therefore seems an important component of professional competence. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validity and Usefulness of `Wearable Blood Pressure Sensing' for Detection of Inappropriate Short-Term Blood Pressure Variability in the Elderly

NASA Astrophysics Data System (ADS)

Iijima, Katsuya; Kameyama, Yumi; Akishita, Masahiro; Ouchi, Yasuyoshi; Yanagimoto, Shintaro; Imai, Yasushi; Yahagi, Naoki; Lopez, Guillaume; Shuzo, Masaki; Yamada, Ichiro

An increase in short-term blood pressure (BP) variability is a characteristic feature in the elderly. It makes the management of hemodynamics more difficult, because it is frequently seen disturbed baro-reflex function and increased arterial stiffness, leading to isolated systolic hypertension. Large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular (CV) events in elderly hypertensive patients. Therefore, appropriate control in BP is indispensable to manage lifestyle-related diseases and to prevent subsequent CV events. In addition, accumulating recent reports show that excessive BP variability is also associated with a decline in cognitive function and fall in the elderly. In the clinical settings, we usually evaluate their health condition, mainly with single point BP measurement using cuff inflation. However, unfortunately we are not able to find the close changes in BP by the traditional way. Here, we can show our advantageous approach of continuous BP monitoring using newly developing device `wearable BP sensing' without a cuff stress in the elderly. The new device could reflect systolic BP and its detailed changes, in consistent with cuff-based BP measurement. Our new challenge suggests new possibility of its clinical application with high accuracy.

Individual and contextual determinants of malocclusion in 12-year-old schoolchildren in a Brazilian city.

PubMed

Jordão, Lidia Moraes Ribeiro; Vasconcelos, Daniela Nobre; Moreira, Rafael da Silveira; Freire, Maria do Carmo Matias

2015-01-01

The aim of this study was to describe malocclusion prevalence and its association with individual and contextual factors among Brazilian 12-year-old schoolchildren. This cross-sectional study included data from an oral health survey carried out in Goiânia, Brazil (n = 2,075), and data from the files of the local health authority. The data were collected through oral clinical examinations. The Dental Aesthetic Index (DAI) was used to assess occlusion. The presence of malocclusion (DAI > 25) was used as the dependent variable. The individual independent variables consisted of adolescents' sex and race and their mothers' level of schooling. The clinical variables were caries experience and presence of adverse periodontal condition (calculus and/or gingival bleeding). The contextual variables included type of school and the location of schools in the city's health districts. The Rao-Scott test and multilevel logistic regression were performed. The prevalence of malocclusion was 40.1%. In the final model, significantly higher rates of malocclusion were found among those who attended schools located in less affluent health districts and whose mothers had fewer years of education. Rates were also higher among those presenting calculus and/or gingival bleeding. Malocclusion demonstrated a high prevalence rate and the inequalities in its distribution were determined by individual and contextual factors.

[Comparative study of two treatment methods for acute periodontal abscess].

PubMed

Jin, Dong-mei; Wang, Wei-qian

2012-10-01

The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). The method of supra- and subgingival scaling was rapid and effective in treatment of acute periodontal abscesses.

Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.

PubMed

Moore, Wendy C; Hastie, Annette T; Li, Xingnan; Li, Huashi; Busse, William W; Jarjour, Nizar N; Wenzel, Sally E; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2014-06-01

Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation. Published by Mosby, Inc.

Sputum neutrophils are associated with more severe asthma phenotypes using cluster analysis

PubMed Central

Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Busse, William W.; Jarjour, Nizar N.; Wenzel, Sally E.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

2013-01-01

Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified five asthma subphenotypes that represent the severity spectrum of early onset allergic asthma, late onset severe asthma and severe asthma with COPD characteristics. Analysis of induced sputum from a subset of SARP subjects showed four sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophils (≥2%) and neutrophils (≥40%) had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP at three clinical sites who underwent sputum induction were included in this analysis (n=423). Fifteen variables including clinical characteristics and blood and sputum inflammatory cell assessments were selected by factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n=132) and B (n=127) subjects had mild-moderate early onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of Cluster C (n=117) and D (n=47) subjects who had moderate-severe asthma with frequent health care utilization despite treatment with high doses of inhaled or oral corticosteroids, and in Cluster D, reduced lung function. The majority these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophils were the most important variables determining cluster assignment. Conclusion This multivariate approach identified four asthma subphenotypes representing the severity spectrum from mild-moderate allergic asthma with minimal or eosinophilic predominant sputum inflammation to moderate-severe asthma with neutrophilic predominant or mixed granulocytic inflammation. PMID:24332216

A clinical return-to-work rule for patients with back pain.

PubMed

Dionne, Clermont E; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R; Larocque, Isabelle

2005-06-07

Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18-64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was "return to work in good health" at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%- 94%). A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome.

A clinical return-to-work rule for patients with back pain

PubMed Central

Dionne, Clermont E.; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R.; Larocque, Isabelle

2005-01-01

Background Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. Methods This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18–64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was “return to work in good health” at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. Results The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%– 94%). Interpretation A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome. PMID:15939915

Development of clinical process measures for pediatric burn care: Understanding variation in practice patterns.

PubMed

Kazis, Lewis E; Sheridan, Robert L; Shapiro, Gabriel D; Lee, Austin F; Liang, Matthew H; Ryan, Colleen M; Schneider, Jeffrey C; Lydon, Martha; Soley-Bori, Marina; Sonis, Lily A; Dore, Emily C; Palmieri, Tina; Herndon, David; Meyer, Walter; Warner, Petra; Kagan, Richard; Stoddard, Frederick J; Murphy, Michael; Tompkins, Ronald G

2018-04-01

There has been little systematic examination of variation in pediatric burn care clinical practices and its effect on outcomes. As a first step, current clinical care processes need to be operationally defined. The highly specialized burn care units of the Shriners Hospitals for Children system present an opportunity to describe the processes of care. The aim of this study was to develop a set of process-based measures for pediatric burn care and examine adherence to them by providers in a cohort of pediatric burn patients. We conducted a systematic literature review to compile a set of process-based indicators. These measures were refined by an expert panel of burn care providers, yielding 36 process-based indicators in four clinical areas: initial evaluation and resuscitation, acute excisional surgery and critical care, psychosocial and pain control, and reconstruction and aftercare. We assessed variability in adherence to the indicators in a cohort of 1,076 children with burns at four regional pediatric burn programs in the Shriners Hospital system. The percentages of the cohort at each of the four sites were as follows: Boston, 20.8%; Cincinnati, 21.1%; Galveston, 36.0%; and Sacramento, 22.1%. The cohort included children who received care between 2006 and 2010. Adherence to the process indicators varied both across sites and by clinical area. Adherence was lowest for the clinical areas of acute excisional surgery and critical care, with a range of 35% to 48% across sites, followed by initial evaluation and resuscitation (range, 34%-60%). In contrast, the clinical areas of psychosocial and pain control and reconstruction and aftercare had relatively high adherence across sites, with ranges of 62% to 93% and 71% to 87%, respectively. Of the 36 process indicators, 89% differed significantly in adherence between clinical sites (p < 0.05). Acute excisional surgery and critical care exhibited the most variability. The development of this set of process-based measures represents an important step in the assessment of clinical practice in pediatric burn care. Substantial variation was observed in practices of pediatric burn care. However, further research is needed to link these process-based measures to clinical outcomes. Therapeutic/care management, level IV.

Birth Control in Clinical Trials: Industry Survey of Current Use Practices, Governance, and Monitoring.

PubMed

Stewart, J; Breslin, W J; Beyer, B K; Chadwick, K; De Schaepdrijver, L; Desai, M; Enright, B; Foster, W; Hui, J Y; Moffat, G J; Tornesi, B; Van Malderen, K; Wiesner, L; Chen, C L

2016-03-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives.

Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection: A Multi-Center Study of Clinical Decision Support for Children with Head Trauma.

PubMed

Deakyne, S J; Bajaj, L; Hoffman, J; Alessandrini, E; Ballard, D W; Norris, R; Tzimenatos, L; Swietlik, M; Tham, E; Grundmeier, R W; Kuppermann, N; Dayan, P S

2015-01-01

Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts. To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR. As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity. Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75-89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites. CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition, including prevalence and morbidity, in addition to the goals of the intervention being considered.

Development and validation of a risk calculator predicting exercise-induced ventricular arrhythmia in patients with cardiovascular disease.

PubMed

Hermes, Ilarraza-Lomelí; Marianna, García-Saldivia; Jessica, Rojano-Castillo; Carlos, Barrera-Ramírez; Rafael, Chávez-Domínguez; María Dolores, Rius-Suárez; Pedro, Iturralde

2016-10-01

Mortality due to cardiovascular disease is often associated with ventricular arrhythmias. Nowadays, patients with cardiovascular disease are more encouraged to take part in physical training programs. Nevertheless, high-intensity exercise is associated to a higher risk for sudden death, even in apparently healthy people. During an exercise testing (ET), health care professionals provide patients, in a controlled scenario, an intense physiological stimulus that could precipitate cardiac arrhythmia in high risk individuals. There is still no clinical or statistical tool to predict this incidence. The aim of this study was to develop a statistical model to predict the incidence of exercise-induced potentially life-threatening ventricular arrhythmia (PLVA) during high intensity exercise. 6415 patients underwent a symptom-limited ET with a Balke ramp protocol. A multivariate logistic regression model where the primary outcome was PLVA was performed. Incidence of PLVA was 548 cases (8.5%). After a bivariate model, thirty one clinical or ergometric variables were statistically associated with PLVA and were included in the regression model. In the multivariate model, 13 of these variables were found to be statistically significant. A regression model (G) with a X(2) of 283.987 and a p<0.001, was constructed. Significant variables included: heart failure, antiarrhythmic drugs, myocardial lower-VD, age and use of digoxin, nitrates, among others. This study allows clinicians to identify patients at risk of ventricular tachycardia or couplets during exercise, and to take preventive measures or appropriate supervision. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Kinematic evaluation of the finger's interphalangeal joints coupling mechanism--variability, flexion-extension differences, triggers, locking swanneck deformities, anthropometric correlations.

PubMed

Leijnse, J N A L; Quesada, P M; Spoor, C W

2010-08-26

The human finger contains tendon/ligament mechanisms essential for proper control. One mechanism couples the movements of the interphalangeal joints when the (unloaded) finger is flexed with active deep flexor. This study's aim was to accurately determine in a large finger sample the kinematics and variability of the coupled interphalangeal joint motions, for potential clinical and finger model validation applications. The data could also be applied to humanoid robotic hands. Sixty-eight fingers were measured in seventeen hands in nine subjects. Fingers exhibited great joint mobility variability, with passive proximal interphalangeal hyperextension ranging from zero to almost fifty degrees. Increased measurement accuracy was obtained by using marker frames to amplify finger segment motions. Gravitational forces on the marker frames were not found to invalidate measurements. The recorded interphalangeal joint trajectories were highly consistent, demonstrating the underlying coupling mechanism. The increased accuracy and large sample size allowed for evaluation of detailed trajectory variability, systematic differences between flexion and extension trajectories, and three trigger types, distinct from flexor tendon triggers, involving initial flexion deficits in either proximal or distal interphalangeal joint. The experimental methods, data and analysis should advance insight into normal and pathological finger biomechanics (e.g., swanneck deformities), and could help improve clinical differential diagnostics of trigger finger causes. The marker frame measuring method may be useful to quantify interphalangeal joints trajectories in surgical/rehabilitative outcome studies. The data as a whole provide the most comprehensive collection of interphalangeal joint trajectories for clinical reference and model validation known to us to date. 2010 Elsevier Ltd. All rights reserved.

Inter-hospital variations in caesarean sections. A risk adjusted comparison in the Valencia public hospitals

PubMed Central

Librero, J.; Peiro, S.; Calderon, S. M.

2000-01-01

BACKGROUND—The aim of this study was to describe the variability in caesarean rates in the public hospitals in the Valencia Region, Spain, and to analyse the association between caesarean sections and clinical and extra-clinical factors.
METHODS—Analysis of data contained in the Minimum Basic Data Set (MBDS) compiled for all births in 11 public hospitals in Valencia during 1994-1995 (n=36 819). Bivariate and multivariate analyses were used to evaluate the association between caesarean section rates and specific risk factors. The multivariate model was used to construct predictions about caesarean rates for each hospital, for comparison with rates observed.
RESULTS—Caesarean rates were 17.6% (inter-hospital range: 14.7% to 25.0%), with ample variability between hospitals in the diagnosis of maternal-fetal risk factors (particularly dystocia and fetal distress), and the indication for caesarean in the presence of these factors. Multivariate analysis showed that maternal-fetal risk factors correlated strongly with caesarean section, although extra-clinical factors, such as the day of the week, also correlated positively. After adjusting for the risk factors, the inter-hospital variation in caesarean rates persisted.
CONCLUSIONS—Although certain limitations (imprecision of some diagnoses and information biases in the MBDS) make it impossible to establish unequivocal conclusions, results show a high degree of variability among hospitals when opting for caesarean section. This variability cannot be justified by differences in obstetric risks.


Keywords: hospital utilisation; medical practice variation; caesarean section; administrative databases PMID:10890876

Post Traumatic Stress Disorder/PTSD in adolescent victims of sexual abuse: resilience and social support as protection factors

PubMed Central

Hébert, Martine; Lavoie, Francine; Blais, Martin

2015-01-01

The present analysis explored the contribution of personal (resilience), familial (maternal and paternal support, sibling support) and extra-familial (peer support, other adult) to the prediction of clinical levels of PTSD symptoms in teenagers reporting sexual abuse while controlling for abuse-related variables (type of abuse, severity, and multiple abuse). In a representative sample of high schools students in the province of Quebec, a total of 15.2% of high school girls and 4.4% of high school boys reported a history of child sexual abuse. Sexually abused girls (27.8%) were more likely than boys (14.9%) to obtain scores reaching clinical levels of PTSD symptoms. A logistic hierarchical regression revealed that over and above the characteristics of the sexual abuse experienced, resilience, maternal as well as peer support contributed to the prediction of symptoms of PTSD reaching the clinical threshold. Avenues for intervention practices and prevention among adolescent victims of sexual assault are discussed. PMID:24714884

Thrombosis of the superior sagittal sinus.

PubMed

Kabashi, Serbeze; Muçaj, Sefedin; Ahmetgjekaj, Ilir; Dreshaj, Shemsedin; Ymeri, Halit; Hundozi, Hajrije; Vranica, Sylen; Hasani, Antigona; Shala, Nexhmedin

2010-01-01

Thrombosis of the sinuses is a distinct cerebrovascular disorder that, unlike arterial stroke, most often affects young adults and children. The symptoms and clinical course are highly variable. During the past decade, increased awareness of the diagnosis, improved neuro-imaging techniques, and more effective treatment have improved the prognosis. More than 80% of all patients now have a good neurologic outcome. This review summarizes recent insights into the pathogenesis of sinus thrombosis, risk factors, and clinical and radiological diagnosis and discusses the current evidence and controversies about the best treatment.

Antiplatelet Drugs

PubMed Central

Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

2012-01-01

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

Clinical Efficacy and Its Prognostic Factor of Percutaneous Endoscopic Lumbar Annuloplasty and Nucleoplasty for the Treatment of Patients with Discogenic Low Back Pain.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2017-09-01

The choice of appropriate treatment of discogenic low back pain (DLBP) frequently is difficult. This study sought to identify the clinical efficacy of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) to treat patients with DLBP and to investigate prognostic clinical or radiologic variables. Eighty-nine patients with a diagnosis of DLBP who underwent PELAN were included. Numeric Rating Scale (NRS) for back pain, Oswestry Disability Index % (ODI%), and modified Macnab criteria were measured at short-term (3-4 weeks) and long-term follow-up period (at least 12 months) to investigate clinical efficacy of PELAN. The subjects were defined as successful group in case of 50% or more reduction of NRS, 40% or more reduction of ODI%, and good or excellent response of Macnab criteria. Clinical and radiologic variables were compared between successful and unsuccessful outcomes group to determine prognostic variables. NRS and ODI% were significantly reduced at short- and long-term follow-up after PELAN. Sixty-two (69.7%) and 68 (76.4%) obtained successful NRS reduction and 59 (66.3%) and 68 (76.4%) accomplished successful ODI% reduction at short-term and long-term follow-up, respectively. Successful Mcnab response was found in 61% at short term and 65.2% at long term. Pain during waist flexion among clinical variables was significantly related to good clinical outcomes and Modic change among radiologic variables was significantly related to poor clinical outcomes. PELAN provided favorable outcomes in patients with DLBP who were refractory to conservative treatments. Flexion pain was good prognostic, and Modic change was a poor prognostic variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric patients with common variable immunodeficiency: long-term follow-up.

PubMed

Mohammadinejad, P; Aghamohammadi, A; Abolhassani, H; Sadaghiani, M S; Abdollahzade, S; Sadeghi, B; Soheili, H; Tavassoli, M; Fathi, S M; Tavakol, M; Behniafard, N; Darabi, B; Pourhamdi, S; Rezaei, N

2012-01-01

Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. The study population comprised 69 individuals with CVID diagnosed during childhood. The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.

Clinical and Serological Predictors of Suicide in Schizophrenia and Major Mood Disorders.

PubMed

Dickerson, Faith; Origoni, Andrea; Schweinfurth, Lucy A B; Stallings, Cassie; Savage, Christina L G; Sweeney, Kevin; Katsafanas, Emily; Wilcox, Holly C; Khushalani, Sunil; Yolken, Robert

2018-03-01

Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.

Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes.

PubMed

Basanta-Alario, María Luisa; Ferri, Jordi; Civera, Miguel; Martínez-Hervás, Sergio; Ascaso, Juan Francisco; Real, José Tomás

2016-02-01

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM. A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were collected using standard methods to assess the effect of age on the clinical and biochemical phenotype of patients with T2DM. We have noted that patients with T2DM > 70 years old have a clinical and biochemical phenotype different from younger subjects (<60 years) including longer times since diabetes onset, higher diastolic blood pressure levels, and lower body mass index (BMI) values. As regards to biological variables, these patients have lower triglyceride levels, impaired kidney function, and lower HbA1c values. Prevalence of metabolic syndrome is lower in patients with T2DM > 70 years of age. Age was inversely related to parameters associated to metabolic syndrome (BMI, waist circumference, blood pressure, and triglyceride levels). We have defined the clinical and biochemical profile of patients with T2DM > 70 years attending health care centers. In addition, the prevalence of stroke, kidney disease, and distal symmetrical polyneuropathy is higher in patients with T2DM >70 years as compared to younger patients (<60 years). Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Cost-evaluation model for clinical trials in a hospital pharmacy service.

PubMed

Idoate, A; Ortega, A; Carrera, F J; Aldaz, A; Giráldez, J

1995-09-22

A cost-evaluation model was applied to clinical trial protocols to estimate their cost for the hospital pharmacy service. The steps taken in the drug management of clinical research were identified. Fixed costs (common to all clinical trials) and variable costs (peculiar to each clinical trial) were determined for each step. The number of patients, the number of operations, the planned services (receptions, storage, drug dispensing), the timing and difficulty of the study (randomization) were included in the variable costs. The economic assessment of these items was based on the costs of the materials and means used, the cost of staff time and finally the cost of drug storage during the clinical trial. This model was applied to 24 clinical trials carried out in the University Clinic of Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug dispensing, stock management and return drugs account for 94% of the time expended. The approximate cost of the pharmacy providing investigational services was $1,766 per trial or $174 per patient. Drug storage costs were not an important source of expenditure among the variable costs (7.4%). The best way to determine the cost of a trial is to calculate the number of operations.

Prevention of post-operative recurrence of Crohn's disease.

PubMed

Vaughn, Byron Philip; Moss, Alan Colm

2014-02-07

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Association of Intrinsic Motivating Factors and Markers of Physician Well-Being: A National Physician Survey.

PubMed

Tak, Hyo Jung; Curlin, Farr A; Yoon, John D

2017-07-01

Although intrinsic motivating factors play important roles in physician well-being and productivity, most studies have focused on extrinsic motivating factors such as salary and work environment. To examine the association of intrinsic motivators with physicians' career satisfaction, life satisfaction, and clinical commitment, while accounting for established extrinsic motivators as well. A nationally representative survey of 2000 US physicians, fielded October to December 2011. Outcome variables were five measures of physician well-being: career satisfaction, life satisfaction, high life meaning, commitment to direct patient care, and commitment to clinical practice. Primary explanatory variables were sense of calling, personally rewarding hours per day, meaningful, long-term relationships with patients, and burnout. Multivariate logit models with survey design provided nationally representative individual-level estimates. Among 1289 respondents, 85.8% and 86.5% were satisfied with their career and life, respectively; 88.6% had high life meaning; 54.5% and 79.5% intended to retain time in direct patient care and continue clinical practice, respectively. Sense of calling was strongly positively associated with high life meaning (odds ratio [OR] 5.14, 95% confidence interval [95% CI] 2.87-9.19) and commitment to direct patient care (OR 2.50, 95% CI 1.53-4.07). Personally rewarding hours per day were most strongly associated with career satisfaction (OR 5.28, 95% CI 2.72-10.2), life satisfaction (OR 4.46, 95% CI 2.34-8.48), and commitment to clinical practice (OR 3.46, 95% CI 1.87-6.39). Long-term relationships with patients were positively associated with career and life satisfaction and high life meaning. Burnout was strongly negatively associated with all measures of physician well-being. Intrinsic motivators (e.g., calling) were associated with each measure of physician well-being (satisfaction, meaning, and commitment), but extrinsic motivators (e.g., annual income) were not associated with meaning or commitment. Understanding the effects of intrinsic motivators may help inform efforts to support physician well-being.

Signalment, clinical signs, and prognostic indicators associated with high-grade second- or third-degree atrioventricular block in dogs: 124 cases (January 1, 1997-December 31, 1997).

PubMed

Schrope, Donald P; Kelch, William J

2006-06-01

To evaluate signalment, clinical signs, and prognosis associated with high-grade second- or third-degree atrioventricular block (AVB) in dogs. Retrospective case series. 124 dogs. Data were gathered from ECGs, veterinarian questionnaires, echocardiograms, and radiographs submitted for review; compared with data from a large control group; and examined for association between variables and duration of survival. A new classification system for AVB was evaluated. Afghan, Catahoula Leopard Dog, Chow Chow, Cocker Spaniel, German Wirehaired Pointer, and Labrador Retriever breeds were predisposed to high-grade second- or third-degree AVB. Heavier, older, and sexually intact female dogs were overrepresented in the study group. Weakness, lethargy, exercise intolerance, and syncope were the most common clinical signs. The presence of clinical signs was not associated with duration of survival. Dogs with high-grade second-degree AVB had a duration of survival similar to that of dogs with third-degree AVB. Dogs with high-grade second- or third-degree AVB were at high risk for sudden death in the first 6 months after diagnosis. High ventricular escape rhythm rate and narrow escape-complex QRS width were negatively associated with duration of survival. Pacemaker implantation had a significant positive association with survival. Pacemaker implantation should be strongly considered in all dogs with high-grade second- or third-degree AVB regardless of whether clinical signs are evident. If medical treatment is warranted, vagolytic medications may be the best choice. A new classification system for AVB may merit further investigation.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Risk factors for autism: translating genomic discoveries into diagnostics.

PubMed

Scherer, Stephen W; Dawson, Geraldine

2011-07-01

Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a 'standard of care' test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.

Acute clinical recovery from sport-related concussion.

PubMed

Nelson, Lindsay D; Janecek, Julie K; McCrea, Michael A

2013-12-01

Concussion is a highly prevalent injury in contact and collision sports that has historically been poorly understood. An influx of sport-concussion research in recent years has led to a dramatic improvement in our understanding of the injury's defining characteristics and natural history of recovery. In this review, we discuss the current state of knowledge regarding the characteristic features of concussion and typical acute course of recovery, with an emphasis on the aspects of functioning most commonly assessed by clinicians and researchers (e.g., symptoms, cognitive deficits, postural stability). While prototypical clinical recovery is becoming better understood, questions remain regarding what factors (e.g., injury severity, demographic variables, history of prior concussions, psychological factors) may explain individual variability in recovery. Although research concerning individual differences in response to concussion is relatively new, and in many cases limited methodologically, we discuss the evidence about several potential moderators of concussion recovery and point out areas for future research. Finally, we describe how increased knowledge about the negative effects of and recovery following concussion has been translated into clinical guidelines for managing concussed athletes.

Reformulations of practice: beyond experience in paramedic airway management.

PubMed

Mausz, Justin; Donovan, Seanan; McConnell, Meghan; Lapalme, Corey; Webb, Andrea; Feres, Elizabeth; Tavares, Walter

2017-07-01

"Deliberate practice" and "feedback" are necessary for the development of expertise. We explored clinical performance in settings where these features are inconsistent or limited, hypothesizing that even in algorithmic domains of practice, clinical performance reformulates in ways that may threaten patient safety, and that experience fails to predict performance. Paramedics participated in two recorded simulation sessions involving airway management, which were analyzed three ways: first, we identified variations in "decision paths" by coding the actions of the participants according to an airway management algorithm. Second, we identified cognitive schemas driving behavior using qualitative descriptive analysis. Third, clinical performances were evaluated using a global rating scale, checklist, and time to achieve ventilation; the relationship between experience and these metrics was assessed using Pearson's correlation. Thirty participants completed a total of 59 simulations. Mean experience was 7.2 (SD=5.8) years. We observed highly variable practice patterns and identified idiosyncratic decision paths and schemas governing practice. We revealed problematic performance deficiencies related to situation awareness, decision making, and procedural skills. There was no association between experience and clinical performance (Scenario 1: r=0.13, p=0.47; Scenario 2: r=-0.10, p=0.58), or the number of errors (Scenario 1: r=.10, p=0.57; Scenario 2: r=0.25, p=0.17) or the time to achieve ventilation (Scenario 1: r=0.53, p=0.78; Scenario 2: r=0.27, p=0.15). Clinical performance was highly variable when approaching an algorithmic problem, and procedural and cognitive errors were not attenuated by provider experience. These findings suggest reformulations of practice emerge in settings where feedback and deliberate practice are limited.

Predictors of Absenteeism Severity in Truant Youth: A Dimensional and Categorical Analysis

ERIC Educational Resources Information Center

Skedgell, Kyleigh; Kearney, Christopher A.

2016-01-01

The present study examined the relationship between school absenteeism severity and specific clinical and family variables in middle and high school youth aged 11-19 years recruited from two truancy settings. School absenteeism severity was defined as a percentage of full school days missed from the current academic year at the time of assessment…

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Subtypes in 22q11.2 Deletion Syndrome Associated with Behaviour and Neurofacial Morphology

ERIC Educational Resources Information Center

Sinderberry, Brooke; Brown, Scott; Hammond, Peter; Stevens, Angela F.; Schall, Ulrich; Murphy, Declan G. M.; Murphy, Kieran C.; Campbell, Linda E.

2013-01-01

22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among…

High Serum Adiponectin Level Is a Risk Factor for Anemia in Japanese Men: A Prospective Observational Study of 1,029 Japanese Subjects

PubMed Central

Kohno, Kei; Narimatsu, Hiroto; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Sho, Ri; Otani, Katsumi; Ishizawa, Kenichi; Yamashita, Hidetoshi; Kubota, Isao; Ueno, Yoshiyuki; Kato, Takeo; Fukao, Akira; Kayama, Takamasa

2016-01-01

Erythroid abnormalities including anemia and polycythemia are often observed in the general clinical setting. Because recent studies reported that adiponectin negatively affects hematopoiesis, we performed a prospective observational study to assess the relationship between anemia and adiponectin, as well as other parameters, in 1029 Japanese subjects (477 men and 552 women) 40 years of age and older. Body measurements, blood tests, and nutrition intake studies were performed at baseline, and 5 to 7 years later (follow-up). Hemoglobin (Hb) and hematocrit (Hct) levels in men with high serum adiponectin levels were lower at follow-up than at baseline. Multiple regression analysis showed that age, body mass index, adiponectin, and glutamic-pyruvic transaminase were significantly associated with erythroid-related variables (red blood cells, Hb, and Hct) in both men and women (P <0.05). In a logistic regression analysis, adiponectin, fasting blood glucose, and β-natriuretic peptide were significant risk factors for anemia in men, and blood urea nitrogen and amylase were significant risk factors in women. Physical features and nutrient intake were not risk factors for anemia. Our study demonstrates, both clinically and epidemiologically, that a high serum adiponectin level decreases the amounts of erythroid-related variables and is a risk factor for anemia in Japanese men. PMID:27918575

Automated array-based genomic profiling in chronic lymphocytic leukemia: Development of a clinical tool and discovery of recurrent genomic alterations

PubMed Central

Schwaenen, Carsten; Nessling, Michelle; Wessendorf, Swen; Salvi, Tatjana; Wrobel, Gunnar; Radlwimmer, Bernhard; Kestler, Hans A.; Haslinger, Christian; Stilgenbauer, Stephan; Döhner, Hartmut; Bentz, Martin; Lichter, Peter

2004-01-01

B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix–CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression. PMID:14730057

Emotional and Cognitive Variables Associated with Contamination-Related Obsessive-Compulsive Symptoms.

PubMed

García-Soriano, Gemma; Rosell-Clari, Vicent; Serrano, Miguel Ángel

2016-05-23

Different variables have been associated with the development/ maintenance of contamination-related obsessive-compulsive disorder (OCD), although the relevance of these factors has not been clearly established. The present study aimed to analyze the relevance and specificity of these variables. Forty-five women with high scores on obsessive-compulsive contamination symptoms (n = 16) or checking symptoms (n = 15), or non-clinical scores (n = 14) participated in a behavioral approach/avoidance task (BAT) with a contamination-OCD stimulus. Vulnerability variables and participants' emotional, cognitive, physiological and behavioral responses to the BAT were appraised. Results show that fear of illness was a relevant vulnerability variable specific to contamination participants (p = .001; η2 p = .291). Contamination participants responded with significantly higher subjective disgust (p =.001; η2 p = .269), anxiety (p = .001; η2 p = .297), urge to wash (p < .001; η2 p = 370), threat from emotion (p < .001; η2 p = .338) and contamination severity (p = .002; η2 p = .260) appraisals, and with lower behavioral approach (p = .008; η2 p = .208) than the other two groups. Moreover, contamination participants showed lower heart rate acceleration (p = .046; η2 p = .170) and higher contamination likelihood appraisals (p < .001; η2 p = .342) than the non-clinical group. Urge to wash was predicted by state disgust (R 2 change = .346) and threat from emotion (R 2 change = .088). These responses were predicted by general anxiety sensitivity (R 2 change = .161), disgust propensity (R 2 change = .255) and fear of illness (R 2 change = .116), but not by other vulnerability variables such as dysfunctional beliefs about thoughts (Responsibility and Overestimation of threat) or disgust sensitivity. State disgust, threat from disgust, anxiety sensitivity and fear of illness were found to be the most relevant variables in contamination symptoms.

[Clinical, functional and older socio-familiar profile of the community in a district of Lima, Peru].

PubMed

Varela-Pinedo, Luis; Chávez-Jimeno, Helver; Tello-Rodríguez, Tania; Ortiz-Saavedra, Pedro; Gálvez-Cano, Miguel; Casas-Vasquez, Paola; Aliaga-Díaz, Elizabeth; Ciudad-Fernandez, Luis

2015-10-01

To determine the clinical, functional and socio-familiar profile of seniors from a community in a district of Lima, Peru. Descriptive cross-sectional study of a sample of 501 people aged 60 and over living in the San Martin de Porres district. We used a structured questionnaire in which clinical, functional and socio-familiar variables were recorded. A physical evaluation was carried out to assess performance based measures and serum samples were taken for hematological and biochemical examination. The data were presented with descriptive statistics such as frequencies and percentages for categorical variables and means and standard deviations for the numeric variables. A total of 501 older adults were evaluated. The mean age was 71.5 years (±8.9 years). The most common chronic disease was arterial hypertension at 40.9%, followed by rheumatic diseases with 36.9%. 27.7% had some degree of partial or total dependence in activities of daily living, 16.2% had cognitive impairment, 8% lived alone, 58.5% had or were at risk of having a social problem.61% self-rated their health as normal, while 16% rated it as bad or very bad. Seniors in the community of San Martin de Porres in Lima have frequent problems of functional dependence, have or are at risk of social problems, chronic illness and a high frequency of geriatric syndromes and problems.

Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy.

PubMed

Pecceu, Evi; Stebbing, Brittainy; Martinez Pereira, Yolanda; Handel, Ian; Culshaw, Geoff; Hodgkiss-Geere, Hannah; Lawrence, Jessica

2017-12-01

Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p = 0.021). Higher baseline VVTI was associated with higher subsequent scores (p < 0.001). VVTI also correlated with anxiety level (p = 0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma.

[Frontal symptoms, self-perceived stress, and subjective memory complaints in substance abusers].

PubMed

Terán-Mendoza, Oscar; Sira-Ramos, Diayanny; Guerrero-Alcedo, Jesús; Arroyo-Alvarado, Daniela

2016-04-01

Substance addiction is a public health problem considering that every day increases the number of individuals with problem drug use, in this sense it is interesting the study of neuropsychological variables to understand the nature of addiction, understanding that brain circuits are involved in the establishment, maintenance and rehabilitation of the same. To determine the influence of addiction on the frontal symptoms, self-perceived stress and subjective memory complaints, secondly, to analyze how these variables relate to people with addictions and finally, establish differences in them between addicts with and without subjective memory complaints. ISP, EEP-14 and MFE-30 instruments were applied to a sample of 115 substance abusers, and 115 people from non-clinical population, matched for age, sex and educational level. Significant differences are evident between addicted to substances and non-clinical subjects in the emotional scale ISP and MFE-30, also in the clinical sample highly significant correlations between all scales are observed; Finally, among people with addictions who reported memory complaints and those who do not, significant differences are evident on all scales except for the self-perceived stress. It is considered necessary to take into account the levels of self-perceived stress, frontal symptoms and subjective memory complaints in substance abusers, because the executive, attentional and mnemonic problems may affect several variables in the process of treatment and rehabilitation.

How to design and write a clinical research protocol in Cosmetic Dermatology*

PubMed Central

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

Comparative Genome Analysis of Ciprofloxacin-Resistant Pseudomonas aeruginosa Reveals Genes Within Newly Identified High Variability Regions Associated With Drug Resistance Development

PubMed Central

Su, Hsun-Cheng; Khatun, Jainab; Kanavy, Dona M.

2013-01-01

The alarming rise of ciprofloxacin-resistant Pseudomonas aeruginosa has been reported in several clinical studies. Though the mutation of resistance genes and their role in drug resistance has been researched, the process by which the bacterium acquires high-level resistance is still not well understood. How does the genomic evolution of P. aeruginosa affect resistance development? Could the exposure of antibiotics to the bacteria enrich genomic variants that lead to the development of resistance, and if so, how are these variants distributed through the genome? To answer these questions, we performed 454 pyrosequencing and a whole genome analysis both before and after exposure to ciprofloxacin. The comparative sequence data revealed 93 unique resistance strain variation sites, which included a mutation in the DNA gyrase subunit A gene. We generated variation-distribution maps comparing the wild and resistant types, and isolated 19 candidates from three discrete resistance-associated high variability regions that had available transposon mutants, to perform a ciprofloxacin exposure assay. Of these region candidates with transposon disruptions, 79% (15/19) showed a reduction in the ability to gain high-level resistance, suggesting that genes within these high variability regions might enrich for certain functions associated with resistance development. PMID:23808957

Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach.

PubMed

Panazzolo, Diogo G; Sicuro, Fernando L; Clapauch, Ruth; Maranhão, Priscila A; Bouskela, Eliete; Kraemer-Aguiar, Luiz G

2012-11-13

We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. Data from 189 female subjects (34.0 ± 15.5 years, 30.5 ± 7.1 kg/m2), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity. In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis

PubMed Central

de Araújo, Valdelaine Etelvina Miranda; Morais, Maria Helena Franco; Reis, Ilka Afonso; Rabello, Ana; Carneiro, Mariângela

2012-01-01

Background In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). Methodology The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002–2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. Principal Findings Model 1 (period 2002–2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007–2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3–6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2–4.8) and age ≥60 years (OR 2.5; 95%CI 1.5–4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2–10.3), other associated infections (OR 3.2; 95%CI 1.3–7.8), jaundice (OR 10.1; 95%CI 3.7–27.2) and age ≥60 years (OR 3.1; 95%CI 1.4–7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). Conclusions Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower mortality. PMID:22347514

Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

PubMed

Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

2016-05-01

Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

Is a clinical sociolinguistics possible?

PubMed

Ball, M J

1992-01-01

This paper considers the idea of developing a clinical sociolinguistics. Various areas of the field are examined, and the importance of the 'core' area of the correlation of non-linguistic variables with linguistic variables stressed. Issues concerning language and class, region, sex, age and context of utterance are investigated, together with the implications for clinical linguistics. Finally, the difficulty of integrating such issues into clinical assessment is explored, and a tentative step forward suggested along the lines of a 'clinical sociolinguistic checklist'.

VARIABLE SELECTION FOR QUALITATIVE INTERACTIONS IN PERSONALIZED MEDICINE WHILE CONTROLLING THE FAMILY-WISE ERROR RATE

PubMed Central

Gunter, Lacey; Zhu, Ji; Murphy, Susan

2012-01-01

For many years, subset analysis has been a popular topic for the biostatistics and clinical trials literature. In more recent years, the discussion has focused on finding subsets of genomes which play a role in the effect of treatment, often referred to as stratified or personalized medicine. Though highly sought after, methods for detecting subsets with altering treatment effects are limited and lacking in power. In this article we discuss variable selection for qualitative interactions with the aim to discover these critical patient subsets. We propose a new technique designed specifically to find these interaction variables among a large set of variables while still controlling for the number of false discoveries. We compare this new method against standard qualitative interaction tests using simulations and give an example of its use on data from a randomized controlled trial for the treatment of depression. PMID:22023676

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

PubMed Central

Kean, James D.; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-01-01

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831. PMID:26633481

Rural Status, Suicide Ideation, and Telemental Health: Risk Assessment in a Clinical Sample.

PubMed

Tarlow, Kevin R; Johnson, Tina A; McCord, Carly E

2018-06-25

Individuals living in rural areas die by suicide at higher rates than those living in metropolitan areas. Telemental health interventions provide rural residing individuals with access to needed care. Identifying telemental health clients at risk for suicide is an important task for clinicians and policymakers. This study evaluated to what degree rural status and other demographic variables predicted suicide ideation in clients seeking services at a telemental health clinic. Study participants included 457 low-income clients residing in the medically underserved, geographically diverse Brazos Valley region of Texas. Clients completed the patient health questionnaire during their initial counseling appointment, which assessed depression severity and suicide ideation in the 2 weeks prior to assessment. Suicide ideation was common among telemental health clients, with approximately 40% of clients in all demographic groups reporting some recent thoughts of suicide. Rates of suicide ideation did not significantly differ by geographic designation (ie, rural/metropolitan status), gender, or race/ethnicity. However, depression was a strong predictor of recent suicide ideation. Telemental health programs can effectively connect clinicians with rural residing clients who are otherwise isolated from health care services. However, clinicians working in high-need, historically underserved areas should be prepared to encounter a high prevalence of suicide ideation and depression. In these regions, clinical and diagnostic features may be better indicators of suicide ideation than demographic variables. © 2018 National Rural Health Association.

The Danish Neuro-Oncology Registry: establishment, completeness and validity.

PubMed

Hansen, Steinbjørn; Nielsen, Jan; Laursen, René J; Rasmussen, Birthe Krogh; Nørgård, Bente Mertz; Gradel, Kim Oren; Guldberg, Rikke

2016-08-30

The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database completeness of patient registration and validity of data. The completeness of the number of patients registered in the database was evaluated in the study period from January 2009 through December 2014 by comparing cases reported to the DNOR with the Danish National Patient Registry and the Danish Pathology Registry. The data validity of important clinical variables was evaluated by a random sample of 100 patients from the DNOR using the medical records as reference. A total of 2241 patients were registered in the DNOR by December 2014 with an overall patient completeness of 92 %, which increased during the study period (from 78 % in 2009 to 96 % in 2014). Medical records were available for all patients in the validity analyses. Most variables showed a high agreement proportion (56-100 %), with a fair to good chance-corrected agreement (k = 0.43-1.0). The completeness of patient registration was very high (92 %) and the validity of the most important patient data was good. The DNOR is a newly established national database, which is a reliable source for future scientific studies and clinical quality assessments among patients with gliomas.

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

PubMed

Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-12-02

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

Outcomes of patients in clinical trials with ST-segment elevation myocardial infarction among countries with different gross national incomes.

PubMed

Orlandini, Andrés; Díaz, Rafael; Wojdyla, Daniel; Pieper, Karen; Van de Werf, Frans; Granger, Christopher B; Harrington, Robert A; Boersma, Eric; Califf, Robert M; Armstrong, Paul; White, Harvey; Simes, John; Paolasso, Ernesto

2006-03-01

To evaluate whether there is an association between 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) included in clinical trials and country gross national income (GNI). A retrospective analysis of the databases of five randomized trials including 50 310 patients with STEMI (COBALT 7169, GIK-2 2931, HERO-2 17,089, ASSENT-2 17,005, and ASSENT-3 6116 patients) from 53 countries was performed. Countries were divided into three groups according to their GNI based on the World Bank data: low (less than 2900 US dollars), medium (between 2900 US dollars and 9000 US dollars), and high GNI (more than 9000 US dollars per capita). Baseline characteristics, in-hospital management variables, and 30-day outcomes were evaluated. A previously defined logistic regression model was used to adjust for differences in baseline characteristics and to predict mortality. The observed mortality was higher than the predicted mortality in the low (12.1 vs. 11.8%) and in the medium income groups (9.4 vs. 7.9%), whereas it was lower in the high income group (4.9 vs. 5.6%). An inverse relationship between mortality and GNI was observed in STEMI clinical trials. Most of the variability in mortality can be explained by differences in baseline characteristics; however, after adjustment, lower income countries have higher mortality than the expected.

The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism

PubMed Central

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

2017-01-01

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

Clinical features of body dysmorphic disorder in adolescents and adults

PubMed Central

Phillips, Katharine A.; Didie, Elizabeth R.; Menard, William; Pagano, Maria E.; Fay, Christina; Weisberg, Risa B.

2006-01-01

Body dysmorphic disorder (BDD) usually begins during adolescence, but its clinical features have received little investigation in this age group. Two hundred individuals with BDD (36 adolescents; 164 adults) completed interviewer-administered and self-report measures. Adolescents were preoccupied with numerous aspects of their appearance, most often their skin, hair, and stomach. Among the adolescents, 94.3% reported moderate, severe, or extreme distress due to BDD, 80.6% had a history of suicidal ideation, and 44.4% had attempted suicide. Adolescents experienced high rates and levels of impairment in school, work, and other aspects of psychosocial functioning. Adolescents and adults were comparable on most variables, although adolescents had significantly more delusional BDD beliefs and a higher lifetime rate of suicide attempts. Thus, adolescents with BDD have high levels of distress and rates of functional impairment, suicidal ideation, and suicide attempts. BDD’s clinical features in adolescents appear largely similar to those in adults. PMID:16499973

Identifying factors which enhance capacity to engage in clinical education among podiatry practitioners: an action research project.

PubMed

Abey, Sally; Lea, Susan; Callaghan, Lynne; Shaw, Steve; Cotton, Debbie

2015-01-01

Health profession students develop practical skills whilst integrating theory with practice in a real world environment as an important component of their training. Research in the area of practice placements has identified challenges and barriers to the delivery of effective placement learning. However, there has been little research in podiatry and the question of which factors impact upon clinical educators' capacity to engage with the role remains an under-researched area. This paper presents the second phase of an action research project designed to determine the factors that impact upon clinical educators' capacity to engage with the mentorship role. An online survey was developed and podiatry clinical educators recruited through National Health Service (NHS) Trusts. The survey included socio-demographic items, and questions relating to the factors identified as possible variables influencing clinical educator capacity; the latter was assessed using the 'Clinical Educator Capacity to Engage' scale (CECE). Descriptive statistics were used to explore demographic data whilst the relationship between the CECE and socio-demographic factors were examined using inferential statistics in relation to academic profile, career profile and organisation of the placement. The survey response rate was 42 % (n = 66). Multiple linear regression identified four independent variables which explain a significant proportion of the variability of the dependent variable, 'capacity to engage with clinical education', with an adjusted R2 of 0.428. The four variables were: protected mentorship time, clinical educator relationship with university, sign-off responsibility, and volunteer status. The identification of factors that impact upon clinical educators' capacity to engage in mentoring of students has relevance for strategic planning and policy-making with the emphasis upon capacity-building at an individual level, so that the key attitudes and characteristics that are linked with good clinical supervision are preserved.

Correlation of arterial fetal base deficit and lactate changes with severity of variable heart rate decelerations in the near-term ovine fetus.

PubMed

Ross, Michael G; Jessie, Marquis; Amaya, Kevin; Matushewski, Brad; Durosier, L Daniel; Frasch, Martin G; Richardson, Bryan S

2013-04-01

Recent guidelines classify variable decelerations without detail as to degree of depth. We hypothesized that variable deceleration severity is highly correlated with fetal base deficit accumulation. Seven near-term fetal sheep underwent a series of graded umbilical cord occlusions resulting in mild (30 bpm decrease), moderate (60 bpm decrease), or severe (decrease of 90 bpm to baseline <70 bpm) variable decelerations at 2.5 minute intervals. Mild, moderate, and severe variable decelerations increased fetal base deficit (0.21 ± 0.03, 0.27 ± 0.03, and 0.54 ± 0.09 mEq/L per minute) in direct proportion to severity. During recovery, fetal base deficit cleared at 0.12 mEq/L per minute. In this model, ovine fetuses can tolerate repetitive mild and moderate variable decelerations with minimal change in base deficit and lactate. In contrast, repetitive severe variable decelerations may result in significant base deficit increases, dependent on frequency. Modified guideline differentiation of mild/moderate vs severe variable decelerations may aid in the interpretation of fetal heart rate tracings and optimization of clinical management paradigms. Copyright © 2013 Mosby, Inc. All rights reserved.

Analysis of cardiovascular oscillations: A new approach to the early prediction of pre-eclampsia

NASA Astrophysics Data System (ADS)

Malberg, H.; Bauernschmitt, R.; Voss, A.; Walther, T.; Faber, R.; Stepan, H.; Wessel, N.

2007-03-01

Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.

Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

PubMed

Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

2017-03-01

Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

Effect of Embolization Material in the Calculation of Dose Deposition in Arteriovenous Malformations

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

De la Cruz, O. O. Galvan; Moreno-Jimenez, S.; Larraga-Gutierrez, J. M.

2010-12-07

In this work it is studied the impact of the incorporation of high Z materials (embolization material) in the dose calculation for stereotactic radiosurgery treatment for arteriovenous malformations. A statistical analysis is done to establish the variables that may impact in the dose calculation. To perform the comparison pencil beam (PB) and Monte Carlo (MC) calculation algorithms were used. The comparison between both dose calculations shows that PB overestimates the dose deposited. The statistical analysis, for the quantity of patients of the study (20), shows that the variable that may impact in the dose calculation is the volume of themore » high Z material in the arteriovenous malformation. Further studies have to be done to establish the clinical impact with the radiosurgery result.« less

Gender Roles and Acculturation: Relationships With Cancer Screening Among Vietnamese American Women

PubMed Central

Nguyen, Anh B.; Clark, Trenette T.; Belgrave, Faye Z.

2017-01-01

The aim of this study was to examine the influence of demographic variables and the interplay between gender roles and acculturation on breast and cervical cancer screening outcomes among Vietnamese American women. Convenience sampling was used to recruit 100 Vietnamese women from the Richmond, VA, metropolitan area. Women were recruited to participate in a larger cancer screening intervention. All participants completed measures on demographic variables, gender roles, acculturation, and cancer screening variables. Findings indicated that traditional masculine gender roles were associated with increased self-efficacy for breast and cervical cancer screening. Higher levels of acculturation were associated with higher probability of having had a Papanicolaou test. In addition, acculturation moderated the relationship between traditional female gender roles and cancer screening variables. For highly acculturated women, higher levels of feminine gender roles predicted higher probability of having had a previous clinical breast exam and higher levels of self-efficacy for cervical cancer screening, while the opposite was true for lower acculturated women. The findings of this study indicate the important roles that sociodemographic variables, gender roles, and acculturation play in affecting health attitudes and behaviors among Vietnamese women. These findings also help to identify a potentially high-risk subgroup and existing gaps that need to be targeted by preventive interventions. PMID:24491129

Gender roles and acculturation: relationships with cancer screening among Vietnamese American women.

PubMed

Nguyen, Anh B; Clark, Trenette T; Belgrave, Faye Z

2014-01-01

The aim of this study was to examine the influence of demographic variables and the interplay between gender roles and acculturation on breast and cervical cancer screening outcomes among Vietnamese American women. Convenience sampling was used to recruit 100 Vietnamese women from the Richmond, VA, metropolitan area. Women were recruited to participate in a larger cancer screening intervention. All participants completed measures on demographic variables, gender roles, acculturation, and cancer screening variables. Findings indicated that traditional masculine gender roles were associated with increased self-efficacy for breast and cervical cancer screening. Higher levels of acculturation were associated with higher probability of having had a Papanicolaou test. In addition, acculturation moderated the relationship between traditional female gender roles and cancer screening variables. For highly acculturated women, higher levels of feminine gender roles predicted higher probability of having had a previous clinical breast exam and higher levels of self-efficacy for cervical cancer screening, while the opposite was true for lower acculturated women. The findings of this study indicate the important roles that sociodemographic variables, gender roles, and acculturation play in affecting health attitudes and behaviors among Vietnamese women. These findings also help to identify a potentially high-risk subgroup and existing gaps that need to be targeted by preventive interventions.

Female Pattern Hair Loss: a clinical and pathophysiological review*

PubMed Central

Ramos, Paulo Müller; Miot, Hélio Amante

2015-01-01

Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss. PMID:26375223

[Personalization in the medicine of the future : Opportunities and risks].

PubMed

Malek, N P

2017-07-01

Personalized medicine is not a new concept. The renaissance of the term is due to the enormous progress in gene sequencing technology and functional imaging, as well as the development of targeted therapies. Application of these technologies in clinical medicine will necessitate infrastructural as well as organizational and educational changes in the healthcare system. An important change required already in the short-term is the introduction of centralized structures, preferably in university clinics, which adopt these innovations and incorporate them into clinical care. Simultaneously, the collation and use of large quantities of relevant data from highly variable sources must be successfully mastered, in order to pave the way for disruptive technologies such as artificial intelligence.

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Automatic optimization high-speed high-resolution OCT retinal imaging at 1μm

NASA Astrophysics Data System (ADS)

Cua, Michelle; Liu, Xiyun; Miao, Dongkai; Lee, Sujin; Lee, Sieun; Bonora, Stefano; Zawadzki, Robert J.; Mackenzie, Paul J.; Jian, Yifan; Sarunic, Marinko V.

2015-03-01

High-resolution OCT retinal imaging is important in providing visualization of various retinal structures to aid researchers in better understanding the pathogenesis of vision-robbing diseases. However, conventional optical coherence tomography (OCT) systems have a trade-off between lateral resolution and depth-of-focus. In this report, we present the development of a focus-stacking optical coherence tomography (OCT) system with automatic optimization for high-resolution, extended-focal-range clinical retinal imaging. A variable-focus liquid lens was added to correct for de-focus in real-time. A GPU-accelerated segmentation and optimization was used to provide real-time layer-specific enface visualization as well as depth-specific focus adjustment. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the ONH, from which we extracted clinically-relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture.

Homework compliance counts in cognitive-behavioral therapy.

PubMed

Lebeau, Richard T; Davies, Carolyn D; Culver, Najwa C; Craske, Michelle G

2013-01-01

Prior research has demonstrated that there is some association between treatment engagement and treatment outcome in behavioral therapy for anxiety disorders. However, many of these investigations have been limited by weak measurement of treatment engagement variables, failure to control for potentially important baseline variables, and failure to consider various treatment engagement variables simultaneously. The purpose of the present study is to examine the relationship between two treatment engagement variables (treatment expectancy and homework compliance) and the extent to which they predict improvement from cognitive-behavioral therapy (CBT) for anxiety disorders. 84 adults with a DSM-IV-defined principal anxiety disorder took part in up to 12 sessions of CBT or acceptance and commitment therapy. Pre- and post-treatment disorder severity was assessed using clinical severity ratings from a semi-structured diagnostic interview. Participants made ratings of treatment expectancy after the first session. Homework compliance was assessed each session by the treating clinician. Contrary to hypotheses, treatment expectancy and homework compliance were poorly correlated. Regression analyses revealed that homework compliance, but not treatment expectancy, predicted a significant portion of the variance in treatment outcome (10%). The present research suggests that although treatment expectation and homework compliance likely represent unique constructs of treatment engagement, homework compliance may be the more important treatment engagement variable for outcomes. The present research suggests that improvement of homework compliance has the potential to be a highly practical and effective way to improve clinical outcomes in CBT targeting anxiety disorders.

Liver Transplantation for Fulminant Hepatic Failure

PubMed Central

Farmer, Douglas G.; Anselmo, Dean M.; Ghobrial, R. Mark; Yersiz, Hasan; McDiarmid, Suzanne V.; Cao, Carlos; Weaver, Michael; Figueroa, Jesus; Khan, Khurram; Vargas, Jorge; Saab, Sammy; Han, Steven; Durazo, Francisco; Goldstein, Leonard; Holt, Curtis; Busuttil, Ronald W.

2003-01-01

Objective To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. Summary Background Data FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. Methods A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. Results Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and ICU-bound. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. Conclusions This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome. PMID:12724633

Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

PubMed

Schultze, A E; Irizarry, A R

2017-02-01

Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

PubMed

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.

Testing the 4Rs and 2Ss Multiple Family Group intervention: study protocol for a randomized controlled trial.

PubMed

Acri, Mary; Hamovitch, Emily; Mini, Maria; Garay, Elene; Connolly, Claire; McKay, Mary

2017-12-04

Oppositional defiant disorder (ODD) is a major mental health concern and highly prevalent among children living in poverty-impacted communities. Despite that treatments for ODD are among the most effective, few children living in poverty receive these services due to substantial barriers to access, as well as difficulties in the uptake and sustained adoption of evidence-based practices (EBPs) in community settings. The purpose of this study is to examine implementation processes that impact uptake of an evidence-based practice for childhood ODD, and the impact of a Clinic Implementation Team (CIT)-driven structured adaptation to enhance its fit within the public mental health clinic setting. This study, a Hybrid Type II effectiveness-implementation research trial, blends clinical effectiveness and implementation research methods to examine the impact of the 4Rs and 2Ss Multiple Family Group (MFG) intervention, family level mediators of child outcomes, clinic/provider-level mediators of implementation, and the impact of CITs on uptake and long-term utilization of this model. All New York City public outpatient mental health clinics have been invited to participate. A sampling procedure that included randomization at the agency level and a sub-study to examine the impact of clinic choice upon outcomes yielded a distribution of clinics across three study conditions. Quantitative data measuring child outcomes, organizational factors and implementation fidelity will be collected from caregivers and providers at baseline, 8, and 16 weeks from baseline, and 6 months from treatment completion. The expected participation is 134 clinics, 268 providers, and 2688 caregiver/child dyads. We will use mediation analysis with a multi-level Structural Equation Modeling (SEM) (MSEM including family level variables, provider variables, and clinic variables), as well as mediation tests to examine study hypotheses. The aim of the study is to generate knowledge about effectiveness and mediating factors in the treatment of ODDs in children in the context of family functioning, and to propose an innovative approach to the adaptation and implementation of new treatment interventions within clinic settings. The proposed CIT adaptation and implementation model has the potential to enhance implementation and sustainability, and ultimately increase the extent to which effective interventions are available and can impact children and families in need of services for serious behavior problems. ClinicalTrials.gov, ID: NCT02715414 . Registered on 3 March 2016.

Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program.

PubMed

Jones, Craig A; Clement, Loran T; Morphew, Tricia; Kwong, Kenny Yat Choi; Hanley-Lopez, Jean; Lifson, Francene; Opas, Lawrence; Guterman, Jeffrey J

2007-06-01

National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

PubMed Central

Goldstein, Lori J.; Gray, Robert; Badve, Sunil; Childs, Barrett H.; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L.; Ravdin, Peter M.; Davidson, Nancy E.; Sledge, George W.; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Sparano, Joseph A.

2008-01-01

Purpose Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments. PMID:18678838

Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

PubMed

Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

2008-09-01

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Artificial pancreas (AP) clinical trial participants' acceptance of future AP technology.

PubMed

Bevier, Wendy C; Fuller, Serena M; Fuller, Ryan P; Rubin, Richard R; Dassau, Eyal; Doyle, Francis J; Jovanovič, Lois; Zisser, Howard C

2014-09-01

Artificial pancreas (AP) systems are currently an active field of diabetes research. This pilot study examined the attitudes of AP clinical trial participants toward future acceptance of the technology, having gained firsthand experience. After possible influencers of AP technology adoption were considered, a 34-question questionnaire was developed. The survey assessed current treatment satisfaction, dimensions of clinical trial participant motivation, and variables of the technology acceptance model (TAM). Forty-seven subjects were contacted to complete the survey. The reliability of the survey scales was tested using Cronbach's α. The relationship of the factors to the likelihood of AP technology adoption was explored using regression analysis. Thirty-six subjects (76.6%) completed the survey. Of the respondents, 86.1% were either highly likely or likely to adopt the technology once available. Reliability analysis of the survey dimensions revealed good internal consistency, with scores of >0.7 for current treatment satisfaction, convenience (motivation), personal health benefit (motivation), perceived ease of use (TAM), and perceived usefulness (TAM). Linear modeling showed that future acceptance of the AP was significantly associated with TAM and the motivation variables of convenience plus the individual item benefit to others (R(2)=0.26, P=0.05). When insulin pump and continuous glucose monitor use were added, the model significance improved (R(2)=0.37, P=0.02). This pilot study demonstrated that individuals with direct AP technology experience expressed high likelihood of future acceptance. Results support the factors of personal benefit, convenience, perceived usefulness, and perceived ease of use as reliable scales that suggest system adoption in this highly motivated patient population.

Generalized Growth of Estuarine, Household and Clinical Isolates of Pseudomonas aeruginosa.

PubMed

Diaz, Kelly E; Remold, Susanna K; Onyiri, Ogochukwu; Bozeman, Maura; Raymond, Peter A; Turner, Paul E

2018-01-01

Pseudomonas aeruginosa is an opportunistic pathogen of particular concern to immune-compromised people, such as cystic fibrosis patients and burn victims. These bacteria grow in built environments including hospitals and households, and in natural environments such as rivers and estuaries. However, there is conflicting evidence whether recent environments like the human lung and open ocean affect P. aeruginosa growth performance in alternate environments. We hypothesized that bacteria recently isolated from dissimilar habitats should grow differently in media containing artificial versus natural resources. To test this idea, we examined growth of P. aeruginosa isolates from three environments (estuary, household, and clinic) in three media types: minimal-glucose lab medium, and media prepared from sugar maple leaves or big bluestem grass. We used automated spectrophotometry to measure high-resolution growth curves for all isolate by media combinations, and studied two fitness parameters: growth rate and maximum population density. Results showed high variability in growth rate among isolates, both overall and in its dependence on assay media, but this variability was not associated with habitat of isolation. In contrast, total growth (change in absorbance over the experiment) differed overall among habitats of isolation, and there were media-specific differences in mean total growth among habitats of isolation, and in among-habitat variability in the media-specific response. This was driven primarily by greater total growth of estuary isolates when compared with those from other habitats of origin, and greater media-specific variability among household isolates than those from other habitats of origin. Taken together, these results suggest that for growth rate P. aeruginosa bacteria appear to be broad generalists without regard to current or recent habitat, whereas for total growth a signature of recent ecological history can be detected.

Clinical and veterinary isolates of Salmonella enterica serovar Enteritidis defective in lipopolysaccharide O-chain polymerization

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

Guard-Petter, J.; Parker, C.T.; Asokan, K.

1999-05-01

Twelve human and chicken isolates of Salmonella enterica serovar Enteritidis belonging to phage types 4, 8, 13a, and 23 were characterized for variability in lipopolysaccharide (LPS) composition. Isolates were differentiated into two groups, i.e., those that lacked immunoreactive O-chain, termed rough isolates, and those that had immunoreactive O-chain, termed smooth isolates. Isolates within these groups could be further differentiated by LPS compositional differences as detected by gel electrophoresis and gas liquid chromatography of samples extracted with water, which yielded significantly more LPS in comparison to phenol-chloroform extraction. The rough isolates were of two types, the O-antigen synthesis mutants and themore » O-antigen polymerization (wzy) mutants. Smooth isolates were also of two types, one producing low-molecular-weight (LMW) LPS and the other producing high-molecular-weight (HMW) LPS. To determine the genetic basis for the O-chain variability of the smooth isolates, the authors analyzed the effects of a null mutation in the O-chain length determinant gene, wzz (cld) of serovar Typhimurium. This mutation results in a loss of HMW LPS; however, the LMW LPS of this mutant was longer and more glucosylated than that from clinical isolates of serovar Enteritidis. Cluster analysis of these data and of those from two previously characterized isogenic strains of serovar Enteritidis that had different virulence attributes indicated that glucosylation of HMW LPS (via oafR function) is variable and results in two types of HMW structures, one that is highly glucosylated and one that is minimally glucosylated. These results strongly indicate that naturally occurring variability in wzy, wzz, and oafR function can be used to subtype isolates of serovar Enteritidis during epidemiological investigations.« less

Objective Evaluation of Vergence Disorders and a Research-Based Novel Method for Vergence Rehabilitation

PubMed Central

Kapoula, Zoï; Morize, Aurélien; Daniel, François; Jonqua, Fabienne; Orssaud, Christophe; Brémond-Gignac, Dominique

2016-01-01

Purpose We performed video-oculography to evaluate vergence eye movement abnormalities in students diagnosed clinically with vergence disorders. We tested the efficiency of a novel rehabilitation method and evaluated its benefits with video-oculography cross-correlated with clinical tests and symptomatology. Methods A total of 19 students (20–27 years old) underwent ophthalmologic, orthoptic examination, and a vergence test coupled with video-oculography. Eight patients were diagnosed with vergence disorders with a high symptomatology score (CISS) and performed a 5-week session of vergence rehabilitation. Vergence and rehabilitation tasks were performed with a trapezoid surface of light emitting diodes (LEDs) and adjacent buzzers (US 8851669). We used a novel Vergence double-step (Vd-s) protocol: the target stepped to a second position before the vergence movement completion. Afterward the vergence test was repeated 1 week and 1 month later. Results Abnormally increased intertrial variability was observed for many vergence parameters (gain, duration, and speed) for the subjects with vergence disorders. High CISS scores were correlated with variability and increased latency. After the Vd-s, variability of all parameters dropped to normal or better levels. Moreover, the convergence and divergence latency diminished significantly to levels better than normal; benefits were maintained 1 month after completion of Vd-s. CISS scores dropped to normal level, which was maintained up to 1 year. Conclusions and Translational Relevance: Intertrial variability is the major marker of vergence disorders. The Vd-s research-based method leads to normalization of vergence properties and lasting removal of symptoms. The efficiency of the method is due to the spatiotemporal parameters of repetitive trials that stimulate neural plasticity. PMID:26981330

Association between non-cholesterol sterol concentrations and Achilles tendon thickness in patients with genetic familial hypercholesterolemia.

PubMed

Baila-Rueda, Lucía; Lamiquiz-Moneo, Itziar; Jarauta, Estíbaliz; Mateo-Gallego, Rocío; Perez-Calahorra, Sofía; Marco-Benedí, Victoria; Bea, Ana M; Cenarro, Ana; Civeira, Fernando

2018-01-15

Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the clinical expression is highly variable. TX are present in other metabolic diseases that associate increased sterol concentration. If non-cholesterol sterols are involved in the development of TX in FH has not been analyzed. Clinical and biochemical characteristics, non-cholesterol sterols concentrations and Aquilles tendon thickness were determined in subjects with genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann-Whitney test were used accordingly. Categorical variables were compared using a Chi square test. ANOVA and Kruskal-Wallis tests were performed to multiple independent variables comparison. Post hoc adjusted comparisons were performed with Bonferroni correction when applicable. Correlations of parameters in selected groups were calculated applying the non-parametric Spearman correlation procedure. To identify variables associated with Achilles tendon thickness changes, multiple linear regression were applied. Patients with TX presented higher concentrations of non-cholesterol sterols in plasma than patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore, there was a significant association between 5α-cholestanol, β-sitosterol, desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040, respectively). Our results indicate that non-cholesterol sterol concentrations are associated with the presence of TX. Since cholesterol and non-cholesterol sterols are present in the same lipoproteins, further studies would be needed to elucidate their potential role in the development of TX.

Surface-Sensitive Microwear Texture Analysis of Attrition and Erosion.

PubMed

Ranjitkar, S; Turan, A; Mann, C; Gully, G A; Marsman, M; Edwards, S; Kaidonis, J A; Hall, C; Lekkas, D; Wetselaar, P; Brook, A H; Lobbezoo, F; Townsend, G C

2017-03-01

Scale-sensitive fractal analysis of high-resolution 3-dimensional surface reconstructions of wear patterns has advanced our knowledge in evolutionary biology, and has opened up opportunities for translatory applications in clinical practice. To elucidate the microwear characteristics of attrition and erosion in worn natural teeth, we scanned 50 extracted human teeth using a confocal profiler at a high optical resolution (X-Y, 0.17 µm; Z < 3 nm). Our hypothesis was that microwear complexity would be greater in erosion and that anisotropy would be greater in attrition. The teeth were divided into 4 groups, including 2 wear types (attrition and erosion) and 2 locations (anterior and posterior teeth; n = 12 for each anterior group, n = 13 for each posterior group) for 2 tissue types (enamel and dentine). The raw 3-dimensional data cloud was subjected to a newly developed rigorous standardization technique to reduce interscanner variability as well as to filter anomalous scanning data. Linear mixed effects (regression) analyses conducted separately for the dependent variables, complexity and anisotropy, showed the following effects of the independent variables: significant interactions between wear type and tissue type ( P = 0.0157 and P = 0.0003, respectively) and significant effects of location ( P < 0.0001 and P = 0.0035, respectively). There were significant associations between complexity and anisotropy when the dependent variable was either complexity ( P = 0.0003) or anisotropy ( P = 0.0014). Our findings of greater complexity in erosion and greater anisotropy in attrition confirm our hypothesis. The greatest geometric means were noted in dentine erosion for complexity and dentine attrition for anisotropy. Dentine also exhibited microwear characteristics that were more consistent with wear types than enamel. Overall, our findings could complement macrowear assessment in dental clinical practice and research and could assist in the early detection and management of pathologic tooth wear.

Generalized Growth of Estuarine, Household and Clinical Isolates of Pseudomonas aeruginosa

PubMed Central

Diaz, Kelly E.; Remold, Susanna K.; Onyiri, Ogochukwu; Bozeman, Maura; Raymond, Peter A.; Turner, Paul E.

2018-01-01

Pseudomonas aeruginosa is an opportunistic pathogen of particular concern to immune-compromised people, such as cystic fibrosis patients and burn victims. These bacteria grow in built environments including hospitals and households, and in natural environments such as rivers and estuaries. However, there is conflicting evidence whether recent environments like the human lung and open ocean affect P. aeruginosa growth performance in alternate environments. We hypothesized that bacteria recently isolated from dissimilar habitats should grow differently in media containing artificial versus natural resources. To test this idea, we examined growth of P. aeruginosa isolates from three environments (estuary, household, and clinic) in three media types: minimal-glucose lab medium, and media prepared from sugar maple leaves or big bluestem grass. We used automated spectrophotometry to measure high-resolution growth curves for all isolate by media combinations, and studied two fitness parameters: growth rate and maximum population density. Results showed high variability in growth rate among isolates, both overall and in its dependence on assay media, but this variability was not associated with habitat of isolation. In contrast, total growth (change in absorbance over the experiment) differed overall among habitats of isolation, and there were media-specific differences in mean total growth among habitats of isolation, and in among-habitat variability in the media-specific response. This was driven primarily by greater total growth of estuary isolates when compared with those from other habitats of origin, and greater media-specific variability among household isolates than those from other habitats of origin. Taken together, these results suggest that for growth rate P. aeruginosa bacteria appear to be broad generalists without regard to current or recent habitat, whereas for total growth a signature of recent ecological history can be detected. PMID:29599754

Big biomedical data and cardiovascular disease research: opportunities and challenges.

PubMed

Denaxas, Spiros C; Morley, Katherine I

2015-07-01

Electronic health records (EHRs), data generated and collected during normal clinical care, are increasingly being linked and used for translational cardiovascular disease research. Electronic health record data can be structured (e.g. coded diagnoses) or unstructured (e.g. clinical notes) and increasingly encapsulate medical imaging, genomic and patient-generated information. Large-scale EHR linkages enable researchers to conduct high-resolution observational and interventional clinical research at an unprecedented scale. A significant amount of preparatory work and research, however, is required to identify, obtain, and transform raw EHR data into research-ready variables that can be statistically analysed. This study critically reviews the opportunities and challenges that EHR data present in the field of cardiovascular disease clinical research and provides a series of recommendations for advancing and facilitating EHR research.

Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

PubMed Central

Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J. Luis

2016-01-01

Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations. PMID:27232756

Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence.

PubMed

Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J Luis

2016-08-09

Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

Post-standardization of routine creatinine assays: are they suitable for clinical applications.

PubMed

Jassam, Nuthar; Weykamp, Cas; Thomas, Annette; Secchiero, Sandra; Sciacovelli, Laura; Plebani, Mario; Thelen, Marc; Cobbaert, Christa; Perich, Carmen; Ricós, Carmen; Paula, Faria A; Barth, Julian H

2017-05-01

Introduction Reliable serum creatinine measurements are of vital importance for the correct classification of chronic kidney disease and early identification of kidney injury. The National Kidney Disease Education Programme working group and other groups have defined clinically acceptable analytical limits for creatinine methods. The aim of this study was to re-evaluate the performance of routine creatinine methods in the light of these defined limits so as to assess their suitability for clinical practice. Method In collaboration with the Dutch External Quality Assurance scheme, six frozen commutable samples, with a creatinine concentration ranging from 80 to 239  μmol/L and traceable to isotope dilution mass spectrometry, were circulated to 91 laboratories in four European countries for creatinine measurement and estimated glomerular filtration rate calculation. Two out of the six samples were spiked with glucose to give high and low final concentrations of glucose. Results Results from 89 laboratories were analysed for bias, imprecision (%CV) for each creatinine assay and total error for estimated glomerular filtration rate. The participating laboratories used analytical instruments from four manufacturers; Abbott, Beckman, Roche and Siemens. All enzymatic methods in this study complied with the National Kidney Disease Education Programme working group recommended limits of bias of 5% above a creatinine concentration of 100  μmol/L. They also did not show any evidence of interference from glucose. In addition, they also showed compliance with the clinically recommended %CV of ≤4% across the analytical range. In contrast, the Jaffe methods showed variable performance with regard to the interference of glucose and unsatisfactory bias and precision. Conclusion Jaffe-based creatinine methods still exhibit considerable analytical variability in terms of bias, imprecision and lack of specificity, and this variability brings into question their clinical utility. We believe that clinical laboratories and manufacturers should work together to phase out the use of relatively non-specific Jaffe methods and replace them with more specific methods that are enzyme based.

Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

PubMed

Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

2017-01-01

Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001-7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Quantification of myocardium at risk in ST- elevation myocardial infarction: a comparison of contrast-enhanced steady-state free precession cine cardiovascular magnetic resonance with coronary angiographic jeopardy scores.

PubMed

De Palma, Rodney; Sörensson, Peder; Verouhis, Dinos; Pernow, John; Saleh, Nawzad

2017-07-27

Clinical outcome following acute myocardial infarction is predicted by final infarct size evaluated in relation to left ventricular myocardium at risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP) cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing MaR. Evidence of its utility compared to traditional assessment methods and as a surrogate for clinical outcome is needed. Retrospective analysis within a study evaluating post-conditioning during ST elevation myocardial infarction (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was compared with angiographic jeopardy methods. Differences and variability between CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical outcomes were compared to MaR and extent of infarction. MaR showed correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p < 0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was 1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2% (agreement limits -13 to +10.5). Inter-observer variability for the BARI score was 0.56 ± 2.9; 0.42 ± 2.1 for the APPROACH score; -1.4 ± 3.1% for CE-SSFP. Intra-observer variability was 0.15 ± 1.85 for the BARI score; for the APPROACH score 0.19 ± 1.6; and for CE-SSFP -0.58 ± 2.9%. Quantification of MaR with CE-SSFP imaging following STEMI shows high correlation and low bias compared with angiographic scoring and supports its use as a reliable and practical method to determine myocardial salvage in this patient population. Clinical trial registration information for the parent clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier: CT20080014. Registered 04 th January 2008.

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

Treacher Collins syndrome: clinical implications for the paediatrician--a new mutation in a severely affected newborn and comparison with three further patients with the same mutation, and review of the literature.

PubMed

Schlump, Jan-Ulrich; Stein, Anja; Hehr, Ute; Karen, Tanja; Möller-Hartmann, Claudia; Elcioglu, Nursel H; Bogdanova, Nadja; Woike, Hartmut Fritz; Lohmann, Dietmar R; Felderhoff-Mueser, Ursula; Linz, Annette; Wieczorek, Dagmar

2012-11-01

Treacher Collins syndrome (TCS) is the most common and well-known mandibulofacial dysostosis caused by mutations in at least three genes involved in pre-rRNA transcription, the TCOF1, POLR1D and POLR1C genes. We present a severely affected male individual with TCS with a heterozygous de novo frameshift mutation within the TCOF1 gene (c.790_791delAG,p.Ser264GlnfsX7) and compare the clinical findings with three previously unpublished, milder affected individuals from two families with the same mutation. We elucidate typical clinical features of TCS and its clinical implications for the paediatrician and mandibulofacial surgeon, especially in severely affected individuals and give a short review of the literature. The clinical data of these three families illustrate that the phenotype associated with this specific mutation has a wide intra- and interfamilial variability, which confirms that variable expressivity in carriers of TCOF1 mutations is not a simple consequence of the mutation but might be modified by the combination of genetic, environmental and stochastic factors. Being such a highly complex disease treatment of individuals with TCS should be tailored to the specific needs of each individual, preferably by a multidisciplinary team consisting of paediatricians, craniofacial surgeons and geneticists.

Novel approach to characterising individuals with low back-related leg pain: cluster identification with latent class analysis and 12-month follow-up.

PubMed

Stynes, Siobhán; Konstantinou, Kika; Ogollah, Reuben; Hay, Elaine M; Dunn, Kate M

2018-04-01

Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as referred leg pain or sciatica (nerve root involvement). However, within the spectrum of LBLP, we hypothesised that there may be other unrecognised patient subgroups. This study aimed to identify clusters of patients with LBLP using latent class analysis and describe their clinical course. The study population was 609 LBLP primary care consulters. Variables from clinical assessment were included in the latent class analysis. Characteristics of the statistically identified clusters were compared, and their clinical course over 1 year was described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg pain severity and was considered to represent a referred leg pain group with no clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n = 122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe pain and disability, respectively, and response to clinical assessment items suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126) had high pain and disability, longer pain duration, and more comorbidities and was difficult to map to a clinical diagnosis. Most improvement for pain and disability was seen in the first 4 months for all clusters. At 12 months, the proportion of patients reporting recovery ranged from 27% for cluster 5 to 45% for cluster 2 (mild sciatica). This is the first study that empirically shows the variability in profile and clinical course of patients with LBLP including sciatica. More homogenous groups were identified, which could be considered in future clinical and research settings.

Determinants of successful clinical networks: the conceptual framework and study protocol.

PubMed

Haines, Mary; Brown, Bernadette; Craig, Jonathan; D'Este, Catherine; Elliott, Elizabeth; Klineberg, Emily; McInnes, Elizabeth; Middleton, Sandy; Paul, Christine; Redman, Sally; Yano, Elizabeth M

2012-03-13

Clinical networks are increasingly being viewed as an important strategy for increasing evidence-based practice and improving models of care, but success is variable and characteristics of networks with high impact are uncertain. This study takes advantage of the variability in the functioning and outcomes of networks supported by the Australian New South Wales (NSW) Agency for Clinical Innovation's non-mandatory model of clinical networks to investigate the factors that contribute to the success of clinical networks. The objective of this retrospective study is to examine the association between external support, organisational and program factors, and indicators of success among 19 clinical networks over a three-year period (2006-2008). The outcomes (health impact, system impact, programs implemented, engagement, user perception, and financial leverage) and explanatory factors will be collected using a web-based survey, interviews, and record review. An independent expert panel will provide judgements about the impact or extent of each network's initiatives on health and system impacts. The ratings of the expert panel will be the outcome used in multivariable analyses. Following the rating of network success, a qualitative study will be conducted to provide a more in-depth examination of the most successful networks. This is the first study to combine quantitative and qualitative methods to examine the factors that contribute to the success of clinical networks and, more generally, is the largest study of clinical networks undertaken. The adaptation of expert panel methods to rate the impacts of networks is the methodological innovation of this study. The proposed project will identify the conditions that should be established or encouraged by agencies developing clinical networks and will be of immediate use in forming strategies and programs to maximise the effectiveness of such networks.

Does habituation matter? Emotional processing theory and exposure therapy for acrophobia.

PubMed

Baker, Aaron; Mystkowski, Jayson; Culver, Najwa; Yi, Rena; Mortazavi, Arezou; Craske, Michelle G

2010-11-01

Clinically, there is wide subscription to emotional processing theory (EPT; Foa & Kozak, 1986) as a model of therapeutic effectiveness of exposure therapy: EPT purports that exposure is maximal when (1) fear is activated (IFA), (2) fear subsides within sessions (WSH), and (3) fear subsides between sessions (BSH). This study examined these assumptions, using in vivo exposure therapy for 44 students scoring high on acrophobia measures. Results indicated that no EPT variables were consistently predictive of treatment outcome. No support was found for IFA or WSH; measures of BSH were predictive of short-term change, but these effects were attenuated at follow-up. Furthermore, EPT variables were not predictive of each other as previously hypothesized, indicating the variables are not functionally related. Copyright © 2010 Elsevier Ltd. All rights reserved.

Variability of age at onset in siblings with familial Alzheimer disease.

PubMed

Gómez-Tortosa, Estrella; Barquero, M Sagrario; Barón, Manuel; Sainz, M Jose; Manzano, Sagrario; Payno, Maria; Ros, Raquel; Almaraz, Carmen; Gómez-Garré, Pilar; Jiménez-Escrig, Adriano

2007-12-01

Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects. To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD. Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain. Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype. Maternal transmission of AD was significantly more frequent than paternal transmission (P < .001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (< or =5 years) or high (>5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO. There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

A tool for prediction of risk of rehospitalisation and mortality in the hospitalised elderly: secondary analysis of clinical trial data

PubMed Central

Alassaad, Anna; Melhus, Håkan; Hammarlund-Udenaes, Margareta; Bertilsson, Maria; Gillespie, Ulrika; Sundström, Johan

2015-01-01

Objectives To construct and internally validate a risk score, the ‘80+ score’, for revisits to hospital and mortality for older patients, incorporating aspects of pharmacotherapy. Our secondary aim was to compare the discriminatory ability of the score with that of three validated tools for measuring inappropriate prescribing: Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert doctors to Right Treatment (START) and Medication Appropriateness Index (MAI). Setting Two acute internal medicine wards at Uppsala University hospital. Patient data were used from a randomised controlled trial investigating the effects of a comprehensive clinical pharmacist intervention. Participants Data from 368 patients, aged 80 years and older, admitted to one of the study wards. Primary outcome measure Time to rehospitalisation or death during the year after discharge from hospital. Candidate variables were selected among a large number of clinical and drug-specific variables. After a selection process, a score for risk estimation was constructed. The 80+ score was internally validated, and the discriminatory ability of the score and of STOPP, START and MAI was assessed using C-statistics. Results Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid or being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked to a lower risk of the outcome. These variables made up the components of the 80+ score. The C-statistics were 0.71 (80+), 0.57 (STOPP), 0.54 (START) and 0.63 (MAI). Conclusions We developed and internally validated a score for prediction of risk of rehospitalisation and mortality in hospitalised older people. The score discriminated risk better than available tools for inappropriate prescribing. Pending external validation, this score can aid in clinical identification of high-risk patients and targeting of interventions. PMID:25694461

A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance.

PubMed

Short, Steven M; Cogdill, Robert P; D'Amico, Frank; Drennen, James K; Anderson, Carl A

2010-12-01

The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Development and Validation of a Clinic-Based Prediction Tool to Identify Female Athletes at High Risk for Anterior Cruciate Ligament Injury

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Khoury, Jane; Succop, Paul; Hewett, Timothy E.

2012-01-01

Background Prospective measures of high knee abduction moment (KAM) during landing identify female athletes at high risk for anterior cruciate ligament injury. Laboratory-based measurements demonstrate 90% accuracy in prediction of high KAM. Clinic-based prediction algorithms that employ correlates derived from laboratory-based measurements also demonstrate high accuracy for prediction of high KAM mechanics during landing. Hypotheses Clinic-based measures derived from highly predictive laboratory-based models are valid for the accurate prediction of high KAM status, and simultaneous measurements using laboratory-based and clinic-based techniques highly correlate. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods One hundred female athletes (basketball, soccer, volleyball players) were tested using laboratory-based measures to confirm the validity of identified laboratory-based correlate variables to clinic-based measures included in a prediction algorithm to determine high KAM status. To analyze selected clinic-based surrogate predictors, another cohort of 20 female athletes was simultaneously tested with both clinic-based and laboratory-based measures. Results The prediction model (odds ratio: 95% confidence interval), derived from laboratory-based surrogates including (1) knee valgus motion (1.59: 1.17-2.16 cm), (2) knee flexion range of motion (0.94: 0.89°-1.00°), (3) body mass (0.98: 0.94-1.03 kg), (4) tibia length (1.55: 1.20-2.07 cm), and (5) quadriceps-to-hamstrings ratio (1.70: 0.48%-6.0%), predicted high KAM status with 84% sensitivity and 67% specificity (P < .001). Clinic-based techniques that used a calibrated physician’s scale, a standard measuring tape, standard camcorder, ImageJ software, and an isokinetic dynamometer showed high correlation (knee valgus motion, r = .87; knee flexion range of motion, r = .95; and tibia length, r = .98) to simultaneous laboratory-based measurements. Body mass and quadriceps-to-hamstrings ratio were included in both methodologies and therefore had r values of 1.0. Conclusion Clinically obtainable measures of increased knee valgus, knee flexion range of motion, body mass, tibia length, and quadriceps-to-hamstrings ratio predict high KAM status in female athletes with high sensitivity and specificity. Female athletes who demonstrate high KAM landing mechanics are at increased risk for anterior cruciate ligament injury and are more likely to benefit from neuromuscular training targeted to this risk factor. Use of the developed clinic-based assessment tool may facilitate high-risk athletes’ entry into appropriate interventions that will have greater potential to reduce their injury risk. PMID:20595554

Neuropsychological Test Selection for Cognitive Impairment Classification: A Machine Learning Approach

PubMed Central

Williams, Jennifer A.; Schmitter-Edgecombe, Maureen; Cook, Diane J.

2016-01-01

Introduction Reducing the amount of testing required to accurately detect cognitive impairment is clinically relevant. The aim of this research was to determine the fewest number of clinical measures required to accurately classify participants as healthy older adult, mild cognitive impairment (MCI) or dementia using a suite of classification techniques. Methods Two variable selection machine learning models (i.e., naive Bayes, decision tree), a logistic regression, and two participant datasets (i.e., clinical diagnosis, clinical dementia rating; CDR) were explored. Participants classified using clinical diagnosis criteria included 52 individuals with dementia, 97 with MCI, and 161 cognitively healthy older adults. Participants classified using CDR included 154 individuals CDR = 0, 93 individuals with CDR = 0.5, and 25 individuals with CDR = 1.0+. Twenty-seven demographic, psychological, and neuropsychological variables were available for variable selection. Results No significant difference was observed between naive Bayes, decision tree, and logistic regression models for classification of both clinical diagnosis and CDR datasets. Participant classification (70.0 – 99.1%), geometric mean (60.9 – 98.1%), sensitivity (44.2 – 100%), and specificity (52.7 – 100%) were generally satisfactory. Unsurprisingly, the MCI/CDR = 0.5 participant group was the most challenging to classify. Through variable selection only 2 – 9 variables were required for classification and varied between datasets in a clinically meaningful way. Conclusions The current study results reveal that machine learning techniques can accurately classifying cognitive impairment and reduce the number of measures required for diagnosis. PMID:26332171

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics.

PubMed

Tyan, Marina; Espinoza-Cuadros, Fernando; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-11-06

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients' facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. ©Marina Tyan, Fernando Espinoza-Cuadros, Rubén Fernández Pozo, Doroteo Toledano, Eduardo Lopez Gonzalo, Jose Daniel Alcazar Ramirez, Luis Alfonso Hernandez Gomez. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.11.2017.

Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

PubMed Central

Jiang, Xi-Ling; Samant, Snehal; Lesko, Lawrence J.; Schmidt, Stephan

2017-01-01

Acute coronary syndromes (ACS) remain life-threatening disorders that are associated with high morbidity and mortality. Dual-antiplatelet therapy with aspirin and clopidogrel has shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in response to clopidogrel treatment in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y12 receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19 that affect clopidogrel’s pharmacokinetics. While FDA has issued a boxed warning for CYP2C19 poor metabolizers due to a potentially reduced efficacy in these patients, results from multivariate analyses suggest that additional factors, including age, sex, obesity, concurrent diseases and drug-drug interactions, may all contribute to the overall between-subject variability in treatment response. However, the extent to which each of these factors contributes to the overall variability and how they are interrelated is currently unclear. The objective of this review article is to provide a comprehensive update on the different factors that influence clopidogrel’s pharmacokinetics and pharmacodynamics and how they mechanistically contribute to inter-individual differences in response to clopidogrel treatment. PMID:25559342

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Therapeutic Misconception in Psychiatry Research: A Systematic Review.

PubMed

Thong, Ivan Sk; Foo, Meng Yee; Sum, Min Yi; Capps, Benjamin; Lee, Tih-Shih; Ho, Calvin; Sim, Kang

2016-02-29

Therapeutic misconception (TM) denotes the phenomenon in which research subjects conflate research purpose, protocols and procedures with clinical treatment. We examined the prevalence, contributory factors, clinical associations, impact, and collated solutions on TM within psychiatric research, and made suggestions going ahead. Literature search for relevant empirical research papers was conducted until February 2015. Eighty-eight reports were extracted, of which 31 were selected, summarised into different headings for discussion of implications and collated solutions of TM. We found variable and high rates of TM (ranging from 12.5% to 86%) in some psychiatry research populations. Contributory factors to TM included perceived medical roles of researchers, media, research setting and subject factors. Greater TM in affective, neurodevelopmental and psychotic spectrum conditions were associated with demographic variables (such as lower education, increased age), clinical factors (such as poor insight, cognitive deficits, increased symptoms, poorer self-rated quality of health), and social functioning (such as decreased independence). Inattention to TM may lead to frustration, negative impression and abandonment of participation in psychiatry research. Strategies such as the employment of a neutral educator during the informed consent process and education modules may be effective in addressing TM. Further research is warranted to examine the different TM facets, specific clinical correlates and more effective management strategies.

Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.

PubMed

Castiello, Luciano; Sabatino, Marianna; Zhao, Yingdong; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Wang, Ena; Wood, Lauren V; Marincola, Francesco M; Puri, Raj K; Stroncek, David F

2013-02-01

Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers.

Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

PubMed

Márquez-Ávila, Candy Sue; Vizcaíno-Alarcón, Alfredo; García-Delgado, Constanza; Núñez-Martínez, Paulina María; Flores-Ramírez, Francisco; Reyes-de la Rosa, Alejandra del Pilar; Mendelsberg-Fishbein, Paola; Ibarra-Grajeda, Diana; Medina-Bravo, Patricia; Balderrábano-Saucedo, Norma; Esteva-Solsona, Salvador; Márquez-Quiróz, Luz del Carmen; Flores-Cuevas, Arturo; Sánchez-Urbina, Rocío; Morales-Jiménez, Ariadna Berenice; Garibay-Nieto, Nayely; Del Bosque-Garza, Jesús; Pietropaolo-Cienfuegos, Dino; Gutiérrez-Camacho, Claudia; García-Morales, Leticia; Morán-Barroso, Verónica Fabiola

2015-11-01

Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ERPs and Psychopathology. I. Behavioral process issues.

PubMed

Roth, W T; Tecce, J J; Pfefferbaum, A; Rosenbloom, M; Callaway, E

1984-01-01

The clinical study of ERPs has an inherent defect--a self-selection of clinical populations that hampers equating of clinically defined groups on factors extraneous to the independent variables. Such ex post facto studies increase the likelihood of confounding variables in the interpretation of findings. Hence, the development of lawful relationships between clinical variables and ERPs is impeded and the fulfillment of description, explanation, prediction, and control in brain science is thwarted. Proper methodologies and theory development can increase the likelihood of establishing these lawful relationships. One methodology of potential value in the clinical application of ERPs, particularly in studies of aging, is that of divided attention. Two promising theoretical developments in the understanding of brain functioning and aging are the distraction-arousal hypothesis and the controlled-automatic attention model. The evaluation of ERPs in the study of brain-behavior relations in clinical populations might be facilitated by the differentiation of concurrent, predictive, content, and construct validities.

PRP For the Treatment of Cartilage Pathology

PubMed Central

Kon, Elizaveta; Filardo, Giuseppe; Di Matteo, Berardo; Marcacci, Maurilio

2013-01-01

In recent years biological strategies are being more widely used to treat cartilage lesions. One of the most exploited novel treatments is Platelet-rich Plasma (PRP), whose high content of growth factors is supposed to determine a regenerative stimulus to cartilaginous tissue. Despite many promising in vitro and in vivo studies, when discussing clinical application a clear indication for the use of PRP cannot be assessed. There are initial encouraging clinical data, but only a few randomized controlled trials have been published, so it is not possible to fully endorse this kind of approach for the treatment of cartilage pathology. Furthermore, study comparison is very difficult due to the great variability in PRP preparation methods, cell content and concentration, storage modalities, activation methods and even application protocols. These factors partially explain the lack of high quality controlled trials up to now. This paper discusses the main aspects concerning the basic biology of PRP, the principal sources of variability, and summarizes the available literature on PRP use, both in surgical and conservative treatments. Based on current evidence, PRP treatment should only be indicated for low-grade cartilage degeneration and in case of failure of more traditional conservative approaches. PMID:23730375

Predicting reattendance at a high-risk breast cancer clinic.

PubMed

Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

2015-10-01

The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

Glaucoma Structural and Functional Progression in American and Korean Cohorts

PubMed Central

Kostanyan, Tigran; Sung, Kyung Rim; Schuman, Joel S.; Ling, Yun; Lucy, Katie A.; Bilonick, Richard A.; Ishikawa, Hiroshi; Kagemann, Larry; Lee, Jin Y.; Wollstein, Gadi

2016-01-01

Objective To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. Design Retrospective longitudinal study. Participants 313 eyes from 189 glaucoma and glaucoma suspects, followed for an average of 38 months. Methods All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had ≥5 reliable visits. Main Outcome Measurements The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and severity, disease subtype (high vs. normal tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. Results The Korean cohort was predominantly normal tension glaucoma, while the American cohort was high tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thinner mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean: −0.71 vs. −0.24μm/year, p<0.01). There was no detectable difference in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. Conclusion Ethnicity, baseline severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies. PMID:26778345

The utility of hemoglobin A1c at diagnosis for prediction of future glycemic control in children with type 1 diabetes

PubMed Central

Viswanathan, Vidhya; Sneeringer, M. Rhonda; Miller, Adam; Eugster, Erica A.; DiMeglio, Linda A.

2014-01-01

Introduction We evaluated the relationships of hemoglobin A1c (A1c) at diagnosis of type 1 diabetes (T1DM) to future glycemic control and to a series of clinical variables in children with T1DM. Materials and methods Patients <18 years old diagnosed with T1DM during a one year period who had an A1c at diagnosis and at least one follow-up visit at our center were eligible for inclusion. Baseline variables examined included age, race, gender, symptom duration, admission acuity, anthropometrics, bicarbonate, and A1c. Annual anthropometric and A1c data were also obtained from clinic visits through 4 years after diagnosis. Results We identified 120 children (53 males). Mean age at diagnosis was 7.6 ± 3.9 years. Mean A1c at diagnosis was 10.9 ± 1.9%. A1c at diagnosis correlated with age at diagnosis, symptom duration, and A1c at 3-years, with trends towards correlations at 6 weeks and 4 years. A1c at 1 year correlated highly with A1c at subsequent visits. No other baseline variables correlated with subsequent glycemic control. Conclusions In children with newly diagnosed diabetes, A1cs at diagnosis and one year post diagnosis are related to subsequent glycemic control. Children with high A1cs particularly at one year post diagnosis may benefit from targeted intensification of resources. PMID:21272951

[Modulating variables of work disability in depressive disorders].

PubMed

Catalina Romero, C; Cabrera Sierra, M; Sainz Gutiérrez, J C; Barrenechea Albarrán, J L; Madrid Conesa, A; Calvo Bonacho, E

2011-01-01

To describe the duration of sickness absence in unipolar depression and to determine the relationship of demographic, job-related and clinical variables with length of temporary work disability in depressive disorders. Prospective observational study. A total of 1,292 subjects with depressive disorder diagnosis (ICD-9-CM) were selected claiming sick leave in an Occupational Diseases and Accident sat Work Insurance Scheme (sampling on successive occasions). Descriptive analyses of sickness absence duration, and bivariate (median test) and multivariate analysis (logistic regression) were performed to find relationships between demographic, job-related and clinical variables. Mean duration of sickness absence episodes due to a depressive disorder was 120 days. After multivariate analyses, female sex (p < 0.01), higher age (p < 0.01), lower educational level (p < 0.01), method of payment according to whether self-employed or unemployed workers (p < 0.01) and being referred to both psychiatrist and psychologist (p < 0.01) remained significantly associated with sick leave length. These findings confirm a strong association of depression with long periods of work disability and high absenteeism, and also suggest the need for improvements in functional ability assessment and promotion, treatment and referral of depressed patients. Copyright © 2010 SECA. Published by Elsevier Espana. All rights reserved.

Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

PubMed

Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

2016-01-01

The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (P<0.03). Adequate knowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Adherence to hysterosalpingogram appointments following hysteroscopic sterilization among low income women

PubMed Central

Leyser-Whalen, Ophra; Berenson, Abbey B.

2013-01-01

Background The few studies on post-Essure hysterosalpingogram (HSG) adherence rates show inconsistent results. This study examined associations between sociodemographic variables not examined in prior studies and HSG adherence among low income women. Study Design Medical records of 286 women who underwent sterilization between August 31, 2005 and September 30, 2011 were reviewed. Chi-square and Mann-Whitney tests were used to determine variable associations with HSG adherence. Results The adherence rate for the first HSG was 85.0% (243/286). Variables associated with adherence were: lower education level (p=.01), not working outside the home (p=.04), being married (p<.0001), lower gravidity (p=.03), fewer lifetime number of sexual partners (p<.0001), no sexually transmitted infection history (p<.01), Hispanic ethnicity (p<.0001), Spanish as a primary language (p<.0001) and living further from the clinic (p<.01). Conclusions This study demonstrates that achieving high rates of adherence with the recommended HSG following Essure placement is feasible among low income populations. Furthermore, not speaking English or having to commute a far distance to the clinic do not appear to be barriers. This is encouraging considering the importance of this test to confirm tubal occlusion. PMID:24012097

Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population.

PubMed

Patten, S B; Metz, L M; Reimer, M A

2000-04-01

The objective of this paper was to evaluate the lifetime and point prevalence of major depression in a population-based Multiple Sclerosis (MS) clinic sample, and to describe associations between selected biopsychosocial variables and the prevalence of lifetime major depression in this sample. Subjects who had participated in an earlier study were re-contacted for additional data collection. Eighty-three per cent (n=136) of those eligible consented to participate. Each subject completed the Composite International Diagnostic Interview (CIDI) and an interviewer-administered questionnaire evaluating a series of biopsychosocial variables. The lifetime prevalence of major depression in this sample was 22.8%, somewhat lower than previous estimates in MS clinic populations. Women, those under 35, and those with a family history of major depression had a higher prevalence. Also, subjects reporting high levels of stress and heavy ingestion of caffeine (>400 mg) had a higher prevalence of major depression. As this was a cross-sectional analysis, the direction of causal effect for the observed associations could not be determined. By identifying variables that are associated with lifetime major depression, these data generate hypotheses for future prospective studies. Such studies will be needed to further understand the etiology of depressive disorders in MS.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

PubMed

Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji

2017-01-01

Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

A national survey of pain clinics within the United Kingdom and Ireland focusing on the multidisciplinary team and the incorporation of the extended nursing role.

PubMed

Kailainathan, Pungavi; Humble, Stephen; Dawson, Helen; Cameron, Fiona; Gokani, Shyam; Lidder, Gursimren

2018-02-01

Inconsistencies in the availability and quality of pain service provision have been noted nationally, as have lengthy waiting times for appointments and lack of awareness of the Pain Clinic role. The 2013 NHS England report stated that specialist pain services must offer multispecialty and multidisciplinary pain clinics. This national survey of multidisciplinary pain service provision in the United Kingdom and Ireland provides a snapshot of pain service provision in order to review and highlight what variations exist in multidisciplinary team (MDT) provision and working patterns. A common perception among clinicians is that financial pressures have led to alternate ways of staff utilisation with variable degrees of success. The survey included 143 pain clinics, focusing principally on MDT working patterns, MDT composition and adoption of the extended role. The results identified that the majority of Pain Clinics utilise the MDT approach. However, provision of critical components such as regular MDT meetings is highly variable as is the composition of the MDT itself and also working patterns of the individual clinicians. The survey reports the successful use of the extended roles for specialist nurses in follow up clinics. In contrast, the survey highlights that a large proportion of clinicians surveyed have reservations about both the effectiveness and the safety of utilising specialist nurses in the extended role to see new referrals of complex pain patients to pain clinics. This survey underlines the essential requirement for incorporation of greater MDT working locally and nationally and allocation of appropriate resources to facilitate this.

A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions.

PubMed

Olivry, Thierry; Bizikova, Petra

2010-02-01

Several hydrolysate-based diets have been commercialized for helping diagnose or treat dogs with cutaneous adverse food reactions (CAFR). This systematic review was performed to examine the evidence in favour of reduced immunological and clinical allergenicity of hydrolysates in dogs with CAFR. Citation databases, meeting abstracts and article bibliographies were scanned for relevant citations, and companies were contacted to provide unpublished reports. Eleven studies relevant to this study were identified. Some evidence of reduced serum IgE binding to a soy hydrolysate (1 study) and decreased intradermal test reactivity to hydrolysed proteins (three studies) was found. In four reports, the feeding of dogs suspected of having CAFR with hydrolysate-based diets reduced or eliminated clinical signs in a variable proportion of subjects. The percentage of dogs with CAFR that still reacted to these hydrolysate-based diets could not be assessed, however. Importantly, up to 50% of dogs with CAFR enrolled in three controlled studies exhibited increases in clinical signs after ingesting partial hydrolysates derived from foods to which they were hypersensitive. In conclusion, the limited number of studies undertaken point to reduced - but not eliminated - immunological and clinical allergenicity of hydrolysate-based commercial diets. A variable proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Clinicians must weigh the clinical benefit of these diets versus their high cost and low risk of reduced appetence or gastrointestinal sign development. At this time, hydrolysate-containing diets are probably best used in dogs suspected not to be hypersensitive to their individual components.

Predictive validity of pre-admission assessments on medical student performance.

PubMed

Dabaliz, Al-Awwab; Kaadan, Samy; Dabbagh, M Marwan; Barakat, Abdulaziz; Shareef, Mohammad Abrar; Al-Tannir, Mohamad; Obeidat, Akef; Mohamed, Ayman

2017-11-24

To examine the predictive validity of pre-admission variables on students' performance in a medical school in Saudi Arabia. In this retrospective study, we collected admission and college performance data for 737 students in preclinical and clinical years. Data included high school scores and other standardized test scores, such as those of the National Achievement Test and the General Aptitude Test. Additionally, we included the scores of the Test of English as a Foreign Language (TOEFL) and the International English Language Testing System (IELTS) exams. Those datasets were then compared with college performance indicators, namely the cumulative Grade Point Average (cGPA) and progress test, using multivariate linear regression analysis. In preclinical years, both the National Achievement Test (p=0.04, B=0.08) and TOEFL (p=0.017, B=0.01) scores were positive predictors of cGPA, whereas the General Aptitude Test (p=0.048, B=-0.05) negatively predicted cGPA. Moreover, none of the pre-admission variables were predictive of progress test performance in the same group. On the other hand, none of the pre-admission variables were predictive of cGPA in clinical years. Overall, cGPA strongly predict-ed students' progress test performance (p<0.001 and B=19.02). Only the National Achievement Test and TOEFL significantly predicted performance in preclinical years. However, these variables do not predict progress test performance, meaning that they do not predict the functional knowledge reflected in the progress test. We report various strengths and deficiencies in the current medical college admission criteria, and call for employing more sensitive and valid ones that predict student performance and functional knowledge, especially in the clinical years.

Predictive validity of pre-admission assessments on medical student performance

PubMed Central

Dabaliz, Al-Awwab; Kaadan, Samy; Dabbagh, M. Marwan; Barakat, Abdulaziz; Shareef, Mohammad Abrar; Al-Tannir, Mohamad; Obeidat, Akef

2017-01-01

Objectives To examine the predictive validity of pre-admission variables on students’ performance in a medical school in Saudi Arabia.  Methods In this retrospective study, we collected admission and college performance data for 737 students in preclinical and clinical years. Data included high school scores and other standardized test scores, such as those of the National Achievement Test and the General Aptitude Test. Additionally, we included the scores of the Test of English as a Foreign Language (TOEFL) and the International English Language Testing System (IELTS) exams. Those datasets were then compared with college performance indicators, namely the cumulative Grade Point Average (cGPA) and progress test, using multivariate linear regression analysis. Results In preclinical years, both the National Achievement Test (p=0.04, B=0.08) and TOEFL (p=0.017, B=0.01) scores were positive predictors of cGPA, whereas the General Aptitude Test (p=0.048, B=-0.05) negatively predicted cGPA. Moreover, none of the pre-admission variables were predictive of progress test performance in the same group. On the other hand, none of the pre-admission variables were predictive of cGPA in clinical years. Overall, cGPA strongly predict-ed students’ progress test performance (p<0.001 and B=19.02). Conclusions Only the National Achievement Test and TOEFL significantly predicted performance in preclinical years. However, these variables do not predict progress test performance, meaning that they do not predict the functional knowledge reflected in the progress test. We report various strengths and deficiencies in the current medical college admission criteria, and call for employing more sensitive and valid ones that predict student performance and functional knowledge, especially in the clinical years. PMID:29176032

Bi-exponential T2 analysis of healthy and diseased Achilles tendons: an in vivo preliminary magnetic resonance study and correlation with clinical score.

PubMed

Juras, Vladimir; Apprich, Sebastian; Szomolanyi, Pavol; Bieri, Oliver; Deligianni, Xeni; Trattnig, Siegfried

2013-10-01

To compare mono- and bi-exponential T2 analysis in healthy and degenerated Achilles tendons using a recently introduced magnetic resonance variable-echo-time sequence (vTE) for T2 mapping. Ten volunteers and ten patients were included in the study. A variable-echo-time sequence was used with 20 echo times. Images were post-processed with both techniques, mono- and bi-exponential [T2 m, short T2 component (T2 s) and long T2 component (T2 l)]. The number of mono- and bi-exponentially decaying pixels in each region of interest was expressed as a ratio (B/M). Patients were clinically assessed with the Achilles Tendon Rupture Score (ATRS), and these values were correlated with the T2 values. The means for both T2 m and T2 s were statistically significantly different between patients and volunteers; however, for T2 s, the P value was lower. In patients, the Pearson correlation coefficient between ATRS and T2 s was -0.816 (P = 0.007). The proposed variable-echo-time sequence can be successfully used as an alternative method to UTE sequences with some added benefits, such as a short imaging time along with relatively high resolution and minimised blurring artefacts, and minimised susceptibility artefacts and chemical shift artefacts. Bi-exponential T2 calculation is superior to mono-exponential in terms of statistical significance for the diagnosis of Achilles tendinopathy. • Magnetic resonance imaging offers new insight into healthy and diseased Achilles tendons • Bi-exponential T2 calculation in Achilles tendons is more beneficial than mono-exponential • A short T2 component correlates strongly with clinical score • Variable echo time sequences successfully used instead of ultrashort echo time sequences.

Predictive factors for clinically actionable computed tomography findings in inflammatory bowel disease patients seen in the emergency department with acute gastrointestinal symptoms.

PubMed

Yarur, Andres J; Mandalia, Amar B; Dauer, Ryan M; Czul, Frank; Deshpande, Amar R; Kerman, David H; Abreu, Maria T; Sussman, Daniel A

2014-06-01

The wide use of abdomino-pelvic computed tomography (APCT) in emergency departments (ED) has raised the concern for radiation exposure, costs and potential reactions to contrast agents. The aim of this study was to determine the yield and predictive factors for clinically actionable findings (CAF) in APCTs performed in patients with inflammatory bowel disease (IBD) who visit the ED. We performed a cross-sectional study including patients with IBD who visited the ED. Variables considered were demographics, IBD phenotype, clinical symptoms, IBD medication use prior to ED visit, laboratory values, and imaging results. The primary outcome was a composite of CAF, defined as new, intra-abdominal abscess or tumor, bowel obstruction, fistulae, diverticulitis, choledocholithiasis, or appendicitis. 354 patients were included. One or more CAF were reported in 26.6% of the APCTs (32.1% in CD and 12.8% in UC [p<0.01]). Independent predictive variables of CAF in CD were: CRP level ≥5mg/dl (p=0.04), previous history of IBD surgery (p=0.037), Black race (p<0.01) and low body mass index (p<0.01). None of the study variables predicted CAF in UC. The yield for CAF with APCT in the ED was high for CD patients but minimal for those with UC and was not improved by the use of contrast. Elevated CRP, low BMI, Black race and previous history of IBD surgery predicted CAF in CD but no variables were predictive of CAF in UC. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Postoperative chest tube management: measuring air leak using an electronic device decreases variability in the clinical practice.

PubMed

Varela, Gonzalo; Jiménez, Marcelo F; Novoa, Nuria Maria; Aranda, José Luis

2009-01-01

Since there are no data in the literature regarding variability in the management of postoperative pleural drainages, we have designed a prospective randomized study aimed at measuring inter-observer variability in deciding when to withdraw chest tubes after lung resection and to evaluate if the use of an electronic device to measure postoperative air leak decreases clinical practice variations. Sixty-one patients undergoing pulmonary resection were randomly assigned to one of the following groups: digital group (electronic measure of pleural air leak using Millicore AB DigiVent chest drainage system) or traditional group (standard water seal pleural chamber). Chest tube withdrawal criteria were established in advance. During morning rounds, two thoracic surgeons with comparable clinical experience and blinded to the decision of their counterpart, evaluated chest tube withdrawal criteria and noted whether the tube should be withdrawn or not. Inter-observer variability kappa index and global, positive, and negative agreement rates were calculated on 2 x 2 tables. Each observation episode was considered in the calculation. Fifty-four observations were recorded in the traditional group. Kappa coefficient was 0.37 (overall agreement rate: 0.58; positive agreement rate: 0.72; and negative agreement rate: 0.64). In the digital group, 67 observations were recorded. Kappa coefficient was 0.88 (overall agreement rate: 0.94; positive agreement rate 0.94; and negative agreement rate 0.94). We have demonstrated a high rate of disagreement related to the indication to remove chest tubes after lung resection and the improvement of the agreement rate with the use of an electronic device to measure postoperative air leak and pleural pressures.

T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Pueyo, Esther; Laguna, Pablo

2017-05-19

Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P <0.001). When TMR was dichotomized at TMR=0.040, the SCD rate was significantly higher in the TMR≥0.040 group ( P <0.001). Cox analysis revealed that TMR≥0.040 was strongly associated with SCD, with a hazard ratio of 3.27 ( P <0.001), independently of clinical and ECG-derived variables. No association was found between TMR and pump failure death. This study shows that TMR is specifically associated with SCD in a population of chronic heart failure patients, and it is a better predictor than clinical and ECG-derived variables. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Field evaluation of a prototype paper-based point-of-care fingerstick transaminase test.

PubMed

Pollock, Nira R; McGray, Sarah; Colby, Donn J; Noubary, Farzad; Nguyen, Huyen; Nguyen, The Anh; Khormaee, Sariah; Jain, Sidhartha; Hawkins, Kenneth; Kumar, Shailendra; Rolland, Jason P; Beattie, Patrick D; Chau, Nguyen V; Quang, Vo M; Barfield, Cori; Tietje, Kathy; Steele, Matt; Weigl, Bernhard H

2013-01-01

Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically-defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading-obtained in a target clinical environment, as performed by local practitioners-indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes.

Developing and validating a predictive model for stroke progression.

PubMed

Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

2011-01-01

Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice.

Addiction treatment dropout: exploring patients' characteristics.

PubMed

López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso

2012-01-01

This study explored the characteristics associated with treatment dropout in substance dependence patients. A sample of 122 addicted patients (84 treatment completers and 38 treatment dropouts) who sought outpatient treatment was assessed to collect information on sociodemographic, consumption (assessed by EuropASI), psychopathological (assessed by SCL-90-R), and personality variables (assessed by MCMI-II). Completers and dropouts were compared on all studied variables. According to the results, dropouts scored significantly higher on the EuropASI variables measuring employment/support, alcohol consumption, and family/social problems, as well as on the schizotypal scale of MCMI-II. Because most of the significant differences were found in EuropASI variables, three clusters analyses (2, 3, and 4 groups) based on EuropASI mean scores were carried out to determine clinically relevant information predicting dropout. The most relevant results were obtained when four groups were used. Comparisons between the four groups derived from cluster analysis showed statistically significant differences in the rate of dropout, with one group exhibiting the highest dropout rate. The distinctive characteristics of the group with highest dropout rate included the presence of an increased labor problem combined with high alcohol consumption. Furthermore, this group had the highest scores on three scales of the MCMI-II: phobic, dependent, and schizotypal. The implications of these results for further research and clinical practice are discussed.  Copyright © American Academy of Addiction Psychiatry.

Variable expressivity of the phenotype in two families with brachydactyly type E, craniofacial dysmorphism, short stature and delayed bone age caused by novel heterozygous mutations in the PTHLH gene.

PubMed

Jamsheer, Aleksander; Sowińska-Seidler, Anna; Olech, Ewelina M; Socha, Magdalena; Kozłowski, Kazimierz; Pyrkosz, Antoni; Trzeciak, Tomasz; Materna-Kiryluk, Anna; Latos-Bieleńska, Anna

2016-05-01

Brachydactyly refers to shortening of digits due to hypoplasia or aplasia of bones forming the hands and/or feet. Isolated brachydactyly type E (BDE), which is characterized by shortened metacarpals and/or metatarsals, results in a small proportion of patients from HOXD13 or PTHLH mutations, although in the majority of cases molecular lesion remains unknown. BDE, like other brachydactylies, shows clinical heterogeneity with highly variable intrafamilial and interindividual expressivity. In this study, we investigated two Polish cases (one familial and one sporadic) presenting with BDE and additional symptoms due to novel PTHLH mutations. Apart from BDE, the affected family showed short stature, mild craniofacial dysmorphism and delayed bone age. Sanger sequencing of PTHLH revealed a novel heterozygous frameshift mutation c.258delC(p.N87Tfs*18) in two affected individuals and one relative manifesting mild brachydactyly. The sporadic patient, in addition to BDE, presented with craniofacial dysmorphism, normal stature and bone age, and was demonstrated to carry a de novo heterozygous c.166C>T(p.R56*) mutation. Our paper reports on the two novel truncating PTHLH variants, resulting in variable combination of BDE and other symptoms. Data shown here expand the knowledge on the phenotypic presentation of PTHLH mutations, highlighting significant clinical variability and incomplete penetrance of the PTHLH-related symptoms.

Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis.

PubMed

Weiss, Bettina G; Bachmann, Lucas M; Pfirrmann, Christian W A; Kissling, Rudolf O; Zubler, Veronika

2016-02-01

Discrimination of diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) can be challenging. Usefulness of whole-body magnetic resonance imaging (WB-MRI) in diagnosing spondyloarthritis has been recently proved. We assessed the value of clinical variables alone and in combination with WB-MRI to distinguish between DISH and AS. Diagnostic case-control study: 33 patients with AS and 15 patients with DISH were included. All patients underwent 1.5 Tesla WB-MRI scanning. MR scans were read by a blinded radiologist using the Canadian-Danish Working Group's recommendation. Imaging and clinical variables were identified using the bootstrap. The most important variables from MR and clinical history were assessed in a multivariate fashion resulting in 3 diagnostic models (MRI, clinical, and combined). The discriminative capacity was quantified using the area under the receiver-operating characteristic (ROC) curve. The strength of diagnostic variables was quantified with OR. Forty-eight patients provided 1545 positive findings (193 DISH/1352 AS). The final MR model contained upper anterior corner fat infiltration (32 DISH/181 AS), ankylosis on the vertebral endplate (4 DISH/60 AS), facet joint ankylosis (4 DISH/49 AS), sacroiliac joint edema (11 DISH/91 AS), sacroiliac joint fat infiltration (2 DISH/114 AS), sacroiliac joint ankylosis (2 DISH/119 AS); area under the ROC curve was 0.71, 95% CI 0.64-0.78. The final clinical model contained patient's age and body mass index (area under the ROC curve 0.90, 95% CI 0.89-0.91). The full diagnostic model containing clinical and MR information had an area under the ROC curve of 0.93 (95% CI 0.92-0.95). WB-MRI features can contribute to the correct diagnosis after a thorough conventional workup of patients with DISH and AS.

Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance.

PubMed

Bright, Molly G; Murphy, Kevin

2013-12-01

Cerebrovascular reactivity (CVR) can be mapped using BOLD fMRI to provide a clinical insight into vascular health that can be used to diagnose cerebrovascular disease. Breath-holds are a readily accessible method for producing the required arterial CO2 increases but their implementation into clinical studies is limited by concerns that patients will demonstrate highly variable performance of breath-hold challenges. This study assesses the repeatability of CVR measurements despite poor task performance, to determine if and how robust results could be achieved with breath-holds in patients. Twelve healthy volunteers were scanned at 3 T. Six functional scans were acquired, each consisting of 6 breath-hold challenges (10, 15, or 20 s duration) interleaved with periods of paced breathing. These scans simulated the varying breath-hold consistency and ability levels that may occur in patient data. Uniform ramps, time-scaled ramps, and end-tidal CO2 data were used as regressors in a general linear model in order to measure CVR at the grey matter, regional, and voxelwise level. The intraclass correlation coefficient (ICC) quantified the repeatability of the CVR measurement for each breath-hold regressor type and scale of interest across the variable task performances. The ramp regressors did not fully account for variability in breath-hold performance and did not achieve acceptable repeatability (ICC<0.4) in several regions analysed. In contrast, the end-tidal CO2 regressors resulted in "excellent" repeatability (ICC=0.82) in the average grey matter data, and resulted in acceptable repeatability in all smaller regions tested (ICC>0.4). Further analysis of intra-subject CVR variability across the brain (ICCspatial and voxelwise correlation) supported the use of end-tidal CO2 data to extract robust whole-brain CVR maps, despite variability in breath-hold performance. We conclude that the incorporation of end-tidal CO2 monitoring into scanning enables robust, repeatable measurement of CVR that makes breath-hold challenges suitable for routine clinical practice. © 2013.

Predicting Clinical Gains and Side Effects of Stimulant Medication in Pediatric Attention-Deficit/Hyperactivity Disorder by Combining Measures From qEEG and ERPs in a Cued GO/NOGO Task.

PubMed

Ogrim, Geir; Kropotov, Juri D

2018-06-01

The study aim was to develop 2 scales: predicting clinical gains and risk of acute side effects of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), combining measures from EEG spectra, event-related potentials (ERPs), and a cued visual GO/NOGO task. Based on 4-week systematic medication trials, 87 ADHD patients aged 8 to 17 years were classified as responders (REs, n = 62) or non-REs (n = 25), and belonging to the side effects (SEs, n = 42) or no-SEs (n = 45) groups. Before starting the trial, a 19-channel EEG was registered twice: Test 1 (T1) without medication and T2 on a single dose of stimulant medication a few days before the trial. EEG was registered T1 and T2: 3 minutes eyes-closed, 3 minutes eyes-open, and 20 minutes cued GO/NOGO. EEG spectra, ERPs, omissions, commissions, reaction time (RT), and RT variability were computed. Groups were compared at T1 and T2 on quantitative EEG (qEEG), ERPs and behavioral parameters; effect sizes ( d) were estimated. Variables with d > 0.5 were converted to quartiles, multiplied by corresponding d, and summed to obtain 2 global scales. Six variables differed significantly between REs and non-REs (T1: theta/alpha ratio, P3NOGO amplitude. Differences T2-T1: Omissions, RT variability, P3NOGO, contingent negative variation [CNV]). The global scale d was 1.86. Accuracy (receiver operating characteristic) was 0.92. SEs and no-SEs differed significantly on 4 variables. (T1: RT, T2: novelty component and alpha peak frequency, and RT changes. Global scale d = 1.08 and accuracy = 0.78. Gains and side effects of stimulants in pediatric ADHD can be predicted with high accuracy by combining EEG spectra, ERPs, and behavior from baseline and single-dose tests. ClinicalTrials.gov identifier: NCT02695355.

Correlation between morphological characteristics in spectral-domain-optical coherence tomography, different functional tests and a patient's subjective handicap in acute central serous chorioretinopathy.

PubMed

Gerendas, Bianca S; Kroisamer, Julia-Sophie; Buehl, Wolf; Rezar-Dreindl, Sandra M; Eibenberger, Katharina M; Pablik, Eleonore; Schmidt-Erfurth, Ursula; Sacu, Stefan

2018-01-16

The purpose of this study was to identify quantitatively measurable morphologic optical coherence tomography (OCT) characteristics in patients with an acute episode of central serous chorioretinopathy (CSC) and evaluate their correlation to functional and psychological variables for their use in daily clinical practice. Retinal thickness (RT), the height, area and volume of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the standardized procedures of the Vienna Reading Center. These morphologic characteristics were compared with functional variables [best-corrected visual acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry, fixation stability], and patients' subjective handicap from CSC using the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25). Data from 39 CSC patients were included in this analysis. Three different SRF height measures showed a high negative correlation (r = -0.7) to retinal sensitivity within the central 9°, which was also negatively correlated with SRF area and volume (r = -0.6). The CS score and fixation stability (fixation points within 2°) showed a moderate negative correlation (r = -0.4) with SRF height variables. Comparison of the subjective handicap with morphological characteristics in spectral-domain (SD)-OCT showed SRF height had the highest correlation (r = -0.4) with the subjective problems reported and overall NEI VFQ-25 score. In conclusion, SRF height measured in SD-OCT showed the best correlation with functional variables and patients' subjective handicap caused by the disease and therefore seems to be the best variable to look at in daily clinical routine. Even though area and volume also show a correlation, these cannot be so easily measured as height and are therefore not suggested for daily clinical routine. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Day-by-Day Variability of Home Blood Pressure and Incident Cardiovascular Disease in Clinical Practice: The J-HOP Study (Japan Morning Surge-Home Blood Pressure).

PubMed

Hoshide, Satoshi; Yano, Yuichiro; Mizuno, Hiroyuki; Kanegae, Hiroshi; Kario, Kazuomi

2018-01-01

We assessed the relationship between day-by-day home blood pressure (BP) variability and incident cardiovascular disease (CVD) in clinical practice. J-HOP study (Japan Morning Surge-Home Blood Pressure) participants underwent home BP monitoring in the morning and evening for a 14-day period, and their BP levels and BP variability independent of the mean (VIM) were assessed. Incident CVD events included coronary heart disease and stroke. Cox models were fitted to assess the home BP variability-CVD risk association. Among 4231 participants (mean±SD age, 64.9±10.9 years; 53.3% women; 79.1% taking antihypertensive medication), mean (SD) home systolic BP (SBP) levels over time and VIM SBP were 134.2 (14.3) and 6.8 (2.5) mm Hg, respectively. During a 4-year follow-up period (16 750.3 person-years), 148 CVD events occurred. VIM SBP was associated with CVD risk (hazard ratio per 1-SD increase, 1.32; 95% confidence interval [CI], 1.15-1.52), independently of mean home SBP levels over time and circulating B-type natriuretic peptide levels or urine albumin-to-creatinine ratio. Adding VIM SBP to the CVD prediction model improved the discrimination (C statistic, 0.785 versus 0.770; C statistic difference, 0.015; 95% CI, 0.003-0.028). Changes in continuous net reclassification improvement (0.259; 95% CI, 0.052-0.537), absolute integrated discrimination improvement (0.010; 95% CI, 0.003-0.016), and relative integrated discrimination improvement (0.104; 95% CI, 0.037-0.166) were also observed with the addition of VIM SBP to the CVD prediction models. In addition to the assessments of mean home SBP levels and cardiovascular end-organ damage, home BP variability measurements may provide a clinically useful distinction between high- and low-risk groups among Japanese outpatients. © 2017 American Heart Association, Inc.

Work-related stressors experienced by part-time clinical affiliate nursing faculty in baccalaureate education.

PubMed

Whalen, Kathleen S

2009-01-01

This descriptive and multivariate correlational study identifies work-related situations that were perceived as stressful in a sample of part-time clinical affiliate nursing faculty (n = 91) from a western state who teach in baccalaureate programs. The most stressful conditions include being physically and emotionally drained; working outside regular hours; dealing with the number of role expectations; and receiving inadequate monetary compensation. Subjects reported other specific stressful situations related to their work with clinical agencies, universities, and students. The researcher also examined the relationships between selected background factors (number of years of clinical teaching experience, clinical teacher education, and holding a second job), role stress, and job satisfaction. Even though this sample had a high job satisfaction rating, the variable, role stress, was shown to significantly predict job satisfaction. Lastly, implications for nurse educators in baccalaureate programs are explored.

[Diagnosis of MODY - brief overview for clinical practice].

PubMed

Urbanová, Jana; Brunerová, Ludmila; Brož, Jan

2018-01-01

Maturity Onset Diabetes of the Young (MODY) comprises inherited forms of diabetes mellitus caused by the mutations in the genes involved in the development, differentiation and function of beta-cells. The majority of patients with MODY remains misdiagnosed and erroneously classified as type 1 or type 2 diabetic patients. Correct MODY diagnosis is, however, essential since it enables individualization of treatment, assessment of the prognosis and identification of diabetes among patient´s relatives. Clinical presentation of MODY is highly variable and it could resemble other types of diabetes, thus identification of MODY patients might be difficult. In this review, we describe typical clinical presentation of the most common MODY subtypes, we summarize current diagnostic guidelines in confirmation of MODY and we raise the question of possible need for extension of current clinical criteria indicating a patient for molecular-genetic testing.Key words: clinical course - diagnosis - differential diagnosis - glucokinase - hepatocyte nuclear factors - MODY.

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

PubMed Central

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

2017-01-01

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

Suicide and suicidal behaviour

PubMed Central

Turecki, Gustavo; Brent, David A.

2017-01-01

Summary Suicide is a complex public health problem of global dimension. Suicidal behaviour (SB) shows marked differences between genders, age groups, geographic regions and socio-political realities, and variably associates with different risk factors, underscoring likely etiological heterogeneity. Although there is no effective algorithm to predict suicide in clinical practice, improved recognition and understanding of clinical, psychological, sociological, and biological factors may facilitate the detection of high-risk individuals and assist in treatment selection. Psychotherapeutic, pharmacological, or neuromodulatory treatments of mental disorders can often prevent SB; additionally, regular follow-up of suicide attempters by mental health services is key to prevent future SB. PMID:26385066

A Meta-analysis on Resting State High-frequency Heart Rate Variability in Bulimia Nervosa.

PubMed

Peschel, Stephanie K V; Feeling, Nicole R; Vögele, Claus; Kaess, Michael; Thayer, Julian F; Koenig, Julian

2016-09-01

Autonomic nervous system function is altered in eating disorders. We aimed to quantify differences in resting state vagal activity, indexed by high-frequency heart rate variability comparing patients with bulimia nervosa (BN) and healthy controls. A systematic search of the literature to identify studies eligible for inclusion and meta-analytical methods were applied. Meta-regression was used to identify potential covariates. Eight studies reporting measures of resting high-frequency heart rate variability in individuals with BN (n = 137) and controls (n = 190) were included. Random-effects meta-analysis revealed a sizeable main effect (Z = 2.22, p = .03; Hedge's g = 0.52, 95% CI [0.06;0.98]) indicating higher resting state vagal activity in individuals with BN. Meta-regression showed that body mass index and medication intake are significant covariates. Findings suggest higher vagal activity in BN at rest, particularly in unmedicated samples with lower body mass index. Potential mechanisms underlying these findings and implications for routine clinical care are discussed. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

[Prescribing monitoring in clinical practice: from enlightened empiricism to rational strategies].

PubMed

Buclin, Thierry; Herzig, Lilli

2013-05-15

Monitoring of a medical condition is the periodic measurement of one or several physiological or biological variables to detect a signal regarding its clinical progression or its response to treatment. We distinguish different medical situations between diagnostic, clinical and therapeutic process to apply monitoring. Many clinical, variables can be used for monitoring, once their intrinsic properties (normal range, critical difference, kinetics, reactivity) and external validity (pathophysiological importance, predictive power for clinical outcomes) are established. A formal conceptualization of monitoring is being developed and should support the rational development of monitoring strategies and their validation through appropriate clinical trials.

Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

PubMed

Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

2010-11-01

Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT.

PubMed

Iyaniwura, John E; Elfarnawany, Mai; Riyahi-Alam, Sadegh; Sharma, Manas; Kassam, Zahra; Bureau, Yves; Parnes, Lorne S; Ladak, Hanif M; Agrawal, Sumit K

2017-07-01

The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. Interobserver variability was good (average absolute difference: 0.77 ± 0.42 mm) using standard views and fair (average absolute difference: 0.90 ± 0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ± 0.09 mm for the standard views and 0.38 ± 0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Risk factors correlated with plantar pressure in Chinese patients with type 2 diabetes.

PubMed

Qiu, Xuan; Tian, De-Hu; Han, Chang-Ling; Chen, Wei; Wang, Zhan-Jian; Mu, Zhen-Yun; Li, Xu; Liu, Kuan-Zhi

2013-12-01

Plantar pressure is a key factor for predicting ulceration in the foot of a diabetes patient. We recruited a group of 100 Chinese patients with type 2 diabetes and an age-, sex-, weight-, and height-matched group of 100 Chinese subjects without diabetes. We obtained plantar pressure data using a Footscan(®) gait system (RsScan International, Olen, Belgium) when the subjects with and without diabetes walked barefoot across a sensor platform. We recorded the maximum force, maximum pressure, impulse, pressure-time integral, and loading rate from 10 regions of the foot. We collected the data of 11 history-based variables, 10 anthropometric variables, and three metabolic variables regarding the clinical characteristics of the diabetes patients. Weight was identified as a determining factor for high plantar pressure. Height, the Neuropathy Symptom Score (NSS), and ankle-brachial index (ABI) were correlated positively with plantar pressure measurements, respectively. The sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and fasting blood glucose (FBG) could also explain a portion of the variability of the plantar pressure measurements. However, the correlations were low or weak. High plantar pressure in diabetes patients could be predicted, in part, based on weight, height, NSS, ABI, sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and FBG. Therefore, interventions should be taken specifically before high plantar pressure emerges.

Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

PubMed

Sanchez-Moreno, J; Bonnin, C M; González-Pinto, A; Amann, B L; Solé, B; Balanzá-Martinez, V; Arango, C; Jiménez, E; Tabarés-Seisdedos, R; Garcia-Portilla, M P; Ibáñez, A; Crespo, J M; Ayuso-Mateos, J L; Martinez-Aran, A; Torrent, C; Vieta, E

2018-05-03

The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine.

PubMed

Wu, Alan H B; Christenson, Robert H; Greene, Dina N; Jaffe, Allan S; Kavsak, Peter A; Ordonez-Llanos, Jordi; Apple, Fred S

2018-04-01

This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB, 8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: ( a ) quality control (QC) utilization, ( b ) validation of the lower reportable analytical limits, ( c ) units to be used in reporting measurable concentrations for patients and QC materials, ( d ) 99th percentile sex-specific upper reference limits to define the reference interval; ( e ) criteria required to define hs-cTn assays, ( f ) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, ( g ) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, ( h ) harmonizing and standardizing assay results and the role of commutable materials, ( i ) time to reporting of results from sample receipt and sample collection, and ( j ) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections. © 2017 American Association for Clinical Chemistry.

Mandatory implementation of NICE Guidelines for the care of bipolar disorder and other conditions in England and Wales.

PubMed

Morriss, Richard

2015-09-30

Bipolar disorder is a common long-term mental health condition characterised by episodes of mania or hypomania and depression resulting in disability, early death, and high health and society costs. Public money funds the National Institute of Healthcare and Clinical Excellence (NICE) to produce clinical guidelines by systematically identifying the most up to date research evidence and costing its main recommendations for healthcare organisations and professionals to follow in England and Wales. Most governments, including those of England and Wales, need to improve healthcare but at reduced cost. There is evidence, particularly in bipolar disorder, that systematically following clinical guidelines achieves these outcomes. NICE clinical guidelines, including those regarding bipolar disorder, remain variably implemented. They give clinicians and patients a non-prescriptive basis for deciding their care. Despite the passing of the Health and Social Care Act in 2012 in England requiring all healthcare organisations to consider NICE clinical guidelines in commissioning, delivering, and inspecting healthcare services, healthcare organisations in the National Health Service may ignore them with little accountability and few consequences. There is no mechanism to ensure that healthcare professionals know or consider them. Barriers to their implementation include the lack of political and professional leadership, the complexity of the organisation of care and policy, mistrust of some processes and recommendations of clinical guidelines, and a lack of a clear implementation model, strategy, responsibility, or accountability. Mitigation to these barriers is presented herein. The variability, safety, and quality of healthcare might be improved and its cost reduced if the implementation of NICE clinical guidelines, such as those for bipolar disorder, were made the minimum starting point for clinical decision-making and mandatory responsibilities of all healthcare organisations and professionals.

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.

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

2010-12-01

Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of Visual Acuity Measurements after Autorefraction versus Manual Refraction in Eyes with and without Diabetic Macular Edema

PubMed Central

Sun, Jennifer K.; Qin, Haijing; Aiello, Lloyd Paul; Melia, Michele; Beck, Roy W.; Andreoli, Christopher M.; Edwards, Paul A.; Glassman, Adam R.; Pavlica, Michael R.

2012-01-01

Objective To compare visual acuity (VA) scores after autorefraction versus research protocol manual refraction in eyes of patients with diabetes and a wide range of VA. Methods Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) VA Test© letter score (EVA) was measured after autorefraction (AR-EVA) and after Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction (MR-EVA). Testing order was randomized, study participants and VA examiners were masked to refraction source, and a second EVA utilizing an identical manual refraction (MR-EVAsupl) was performed to determine test-retest variability. Results In 878 eyes of 456 study participants, median MR-EVA was 74 (Snellen equivalent approximately 20/32). Spherical equivalent was often similar for manual and autorefraction (median difference: 0.00, 5th and 95th percentiles −1.75 to +1.13 Diopters). However, on average, MR-EVA results were slightly better than AR-EVA results across the entire VA range. Furthermore, variability between AR-EVA and MR-EVA was substantially greater than the test-retest variability of MR-EVA (P<0.001). Variability of differences was highly dependent on autorefractor model. Conclusions Across a wide range of VA at multiple sites using a variety of autorefractors, VA measurements tend to be worse with autorefraction than manual refraction. Differences between individual autorefractor models were identified. However, even among autorefractor models comparing most favorably to manual refraction, VA variability between autorefraction and manual refraction is higher than the test-retest variability of manual refraction. The results suggest that with current instruments, autorefraction is not an acceptable substitute for manual refraction for most clinical trials with primary outcomes dependent on best-corrected VA. PMID:22159173

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Risk factors and prevalence of burnout syndrome in the nursing profession.

PubMed

Cañadas-De la Fuente, Guillermo A; Vargas, Cristina; San Luis, Concepción; García, Inmaculada; Cañadas, Gustavo R; De la Fuente, Emilia I

2015-01-01

The burnout syndrome is beginning to be regarded as an occupational illness of high prevalence among nursing in Spain. Individuals suffering from the syndrome manifest important health problems. More information about prevalence and risk factors for burnout is needed to prevent the syndrome and to determine the most appropriate clinical interventions when the disorder appears. Burnout levels were evaluated in a group of nurses. The objectives of this study were to estimate the prevalence of burnout, to identify the variables related to burnout and to propose a risk profile for this syndrome among the nursing personnel. The study was carried out in public health centers in Andalusia (Spain). The sample consisted of 676 nursing professionals from public health centers. Dependent variables were the three Burnout dimensions: emotional exhaustion, depersonalization and personal accomplishment. Independent variables were socio-demographic, organizational, personality-related variables. The nurses manifested average to high burnout levels. There were statistically significant differences in burnout levels associated with the following variables: age, gender, marital status, having children, level of healthcare, type of work shift, healthcare service areas and conducting administrative tasks. Burnout was also associated with personality-related variables. The prevalence of burnout among nursing professionals is high. Gender, age, marital status, level of healthcare, work shift and healthcare service areas predicted at least one of the dimensions of the syndrome. Neuroticism, agreeability, extraversion and conscientiousness are personality traits that predict at least two of the dimensions of burnout syndrome in nurses. Therefore, personality factors should be considered in any theory of risk profiles for developing burnout syndrome in the nursing profession. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of variables influencing pharmaceutical interventions to improve medication review efficiency.

PubMed

Cornuault, Lauriane; Mouchel, Victorine; Phan Thi, Thuy-Tan; Beaussier, Hélène; Bézie, Yvonnick; Corny, Jennifer

2018-06-02

Background Clinical pharmacists' involvement has improved patients' care, by suggesting therapeutic optimizations. However, budget restrictions require a prioritization of these activities to focus resources on patients more at risk of medication errors. Objective The aim of our study was to identify variables influencing the formulation of pharmaceutical to improve medication review efficiency. Setting This study was conducted in medical wards of a 643-acute beds hospital in Paris, France. Methods All hospital medical prescriptions of all patients admitted within four medical wards (cardiology, rheumatology, neurology, vascular medicine) were analyzed. The study was conducted in each ward for 2 weeks, during 4 weeks. For each patient, variables prospectively collected were: age, gender, weight, emergency admission, number of high-alert medications and of total drugs prescribed, care unit, serum creatinine. Number of pharmaceutical interventions (PIs) and their type were reported. Main outcome measures Variables influencing the number of pharmaceutical interventions during medication review were identified using simple and multiple linear regressions. Results A total of 2328 drug prescriptions (303 patients, mean age 70.6 years-old) were analyzed. Mean number of hospital drug prescriptions was 7.9. A total of 318 PIs were formulated. Most frequent PIs were drug omission (n = 88, 27.7%), overdosing (n = 69, 21.7%), and underdosing (n = 51, 16.0%). Among variables studied, age, serum creatinine level, number of high-alert medications prescribed and total number of drugs prescribed were significantly associated with the formulation of pharmaceutical interventions (adjusted R 2  = 0.34). Conclusions This study identified variables (age, serum creatinine level, number of high-alert medication, number of prescribed drugs) that may help institutions/pharmacists target their reviews towards patients most likely to require pharmacist interventions.

Dynamic perfusion assessment during perforator flap surgery: an up-to-date

PubMed Central

MUNTEAN, MAXIMILIAN VLAD; MUNTEAN, VALENTIN; ARDELEAN, FILIP; GEORGESCU, ALEXANDRU

2015-01-01

Flap monitoring technology has progressed alongside flap design. The highly variable vascular anatomy and the complexity associated with modern perforator flaps demands dynamic, real-time, intraoperative information about the vessel location, perfusion patterns and flap physiology. Although most surgeons still assess flap perfusion and viability based solely on clinical experience, studies have shown that results may be highly variable and often misleading. Poor judgment of intraoperative perfusion leads to major complications. Employing dynamic perfusion imaging during flap reconstruction has led to a reduced complication rate, lower morbidity, shorter hospital stay, and an overall better result. With the emergence of multiple systems capable of intraoperative flap evaluation, the purpose of this article is to review the two systems that have been widely accepted and are currently used by plastic surgeons: Indocyanine green angiography (ICGA) and dynamic infrared thermography (DIRT). PMID:26609259

Measuring cardiac waste: the premier cardiac waste measures.

PubMed

Lowe, Timothy J; Partovian, Chohreh; Kroch, Eugene; Martin, John; Bankowitz, Richard

2014-01-01

The authors developed 8 measures of waste associated with cardiac procedures to assist hospitals in comparing their performance with peer facilities. Measure selection was based on review of the research literature, clinical guidelines, and consultation with key stakeholders. Development and validation used the data from 261 hospitals in a split-sample design. Measures were risk adjusted using Premier's CareScience methodologies or mean peer value based on Medicare Severity Diagnosis-Related Group assignment. High variability was found in resource utilization across facilities. Validation of the measures using item-to-total correlations (range = 0.27-0.78), Cronbach α (.88), and Spearman rank correlation (0.92) showed high reliability and discriminatory power. Because of the level of variability observed among hospitals, this study suggests that there is opportunity for facilities to design successful waste reduction programs targeting cardiac-device procedures.

Metabolic Tumor Burden Assessed by Dual Time Point [18F]FDG PET/CT in Locally Advanced Breast Cancer: Relation with Tumor Biology.

PubMed

Garcia-Vicente, Ana María; Pérez-Beteta, Julián; Pérez-García, Víctor Manuel; Molina, David; Jiménez-Londoño, German Andrés; Soriano-Castrejón, Angel; Martínez-González, Alicia

2017-08-01

The aim of the study was to investigate the influence of dual time point 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) on the standard uptake value (SUV) and volume-based metabolic variables of breast lesions and their relation with biological characteristics and molecular phenotypes. Retrospective analysis including 67 patients with locally advanced breast cancer (LABC). All patients underwent a dual time point [ 18 F]FDG PET/CT, 1 h (PET-1) and 3 h (PET-2) after [ 18 F]FDG administration. Tumors were segmented following a three-dimensional methodology. Semiquantitative metabolic variables (SUV max , SUV mean , and SUV peak ) and volume-based variables (metabolic tumor volume, MTV, and total lesion glycolysis, TLG) were obtained. Biologic prognostic parameters, such as the hormone receptors status, p53, HER2 expression, proliferation rate (Ki-67), and grading were obtained. Molecular phenotypes and risk-classification [low: luminal A, intermediate: luminal B HER2 (-) or luminal B HER2 (+), and high: HER2 pure or triple negative] were established. Relations between clinical and biological variables with the metabolic parameters were studied. The relevance of each metabolic variable in the prediction of phenotype risk was assessed using a multivariate analysis. SUV-based variables and TLG obtained in the PET-1 and PET-2 showed high and significant correlations between them. MTV and SUV variables (SUV max , SUV mean , and SUV peak ) where only marginally correlated. Significant differences were found between mean SUV variables and TLG obtained in PET-1 and PET-2. High and significant associations were found between metabolic variables obtained in PET-1 and their homonymous in PET-2. Based on that, only relations of PET-1 variables with biological tumor characteristics were explored. SUV variables showed associations with hormone receptors status (p < 0.001 and p = 0.001 for estrogen and progesterone receptor, respectively) and risk-classification according to phenotype (SUV max , p = 0.003; SUV mean , p = 0.004; SUV peak , p = 0.003). As to volume-based variables, only TLG showed association with hormone receptors status (estrogen, p < 0.001; progesterone, p = 0.031), risk-classification (p = 0.007), and grade (p = 0.036). Hormone receptor negative tumors, high-grade tumors, and high-risk phenotypes showed higher TLG values. No association was found between the metabolic variables and Ki-67, HER2, or p53 expression. Statistical differences were found between mean SUV-based variables and TLG obtained in the dual time point PET/CT. Most of PET-derived parameters showed high association with molecular factors of breast cancer. However, dual time point PET/CT did not offer any added value to the single PET acquisition with respect to the relations with biological variables, based on PET-1 SUV, and volume-based variables were predictors of those obtained in PET-2.

Noninvasive characterization of carotid plaque strain.

PubMed

Khan, Amir A; Sikdar, Siddhartha; Hatsukami, Thomas; Cebral, Juan; Jones, Michael; Huston, John; Howard, George; Lal, Brajesh K

2017-06-01

Current risk stratification of internal carotid artery plaques based on diameter-reducing percentage stenosis may be unreliable because ischemic stroke results from plaque disruption with atheroembolization. Biomechanical forces acting on the plaque may render it vulnerable to rupture. The feasibility of ultrasound-based quantification of plaque displacement and strain induced by hemodynamic forces and their relationship to high-risk plaques have not been determined. We studied the feasibility and reliability of carotid plaque strain measurement from clinical B-mode ultrasound images and the relationship of strain to high-risk plaque morphology. We analyzed carotid ultrasound B-mode cine loops obtained in patients with asymptomatic ≥50% stenosis during routine clinical scanning. Optical flow methods were used to quantify plaque motion and shear strain during the cardiac cycle. The magnitude (maximum absolute shear strain rate [MASSR]) and variability (entropy of shear strain rate [ESSR] and variance of shear strain rate [VSSR]) of strain were combined into a composite shear strain index (SSI), which was assessed for interscan repeatability and correlated with plaque echolucency. Nineteen patients (mean age, 70 years) constituting 36 plaques underwent imaging; 37% of patients (n = 7) showed high strain (SSI ≥0.5; MASSR, 2.2; ESSR, 39.7; VSSR, 0.03) in their plaques; the remaining clustered into a low-strain group (SSI <0.5; MASSR, 0.58; ESSR, 21.2; VSSR, 0.002). The area of echolucent morphology was greater in high-strain plaques vs low-strain plaques (28% vs 17%; P = .018). Strain measurements showed low variability on Bland-Altman plots with cluster assignment agreement of 76% on repeated scanning. Two patients developed a stroke during 2 years of follow-up; both demonstrated high SSI (≥0.5) at baseline. Carotid plaque strain is reliably computed from routine B-mode imaging using clinical ultrasound machines. High plaque strain correlates with known high-risk echolucent morphology. Strain measurement can complement identification of patients at high risk for plaque disruption and stroke. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Preliminary definition of improvement in juvenile arthritis.

PubMed

Giannini, E H; Ruperto, N; Ravelli, A; Lovell, D J; Felson, D T; Martini, A

1997-07-01

To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.

Reflections in the clinical practice.

PubMed

Borrell-Carrió, F; Hernández-Clemente, J C

2014-03-01

The purpose of this article is to analyze some models of expert decision and their impact on the clinical practice. We have analyzed decision-making considering the cognitive aspects (explanatory models, perceptual skills, analysis of the variability of a phenomenon, creating habits and inertia of reasoning and declarative models based on criteria). We have added the importance of emotions in decision making within highly complex situations, such as those occurring within the clinical practice. The quality of the reflective act depends, among other factors, on the ability of metacognition (thinking about what we think). Finally, we propose an educational strategy based on having a task supervisor and rectification scenarios to improve the quality of medical decision making. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Gorlin-Goltz Syndrome: An Uncommon Cause of Facial Pain and Asymmetry.

PubMed

Pickrell, Brent B; Nguyen, Harrison P; Buchanan, Edward P

2015-10-01

Gorlin-Goltz syndrome is an underdiagnosed autosomal dominant disorder with variable expressivity that is characterized by an increased predisposition to tumorigenesis of multiple types. The major clinical features include multiple basal cell carcinomas (BCCs) appearing in early childhood, palmar and plantar pits, odontogenic keratocysts of the oral cavity, skeletal defects, craniofacial dysmorphism, and ectopic intracranial calcification. The authors present the clinical course of a 12-year-old girl presenting with facial asymmetry and pain because of previously undiagnosed Gorlin-Goltz syndrome. Early diagnosis and attentive management by a multidisciplinary team are paramount to improving outcomes in patients with this disorder, and this report serves as a paradigm for maintaining a high clinical suspicion, which must be accompanied by an appropriate radiologic workup.

Another Piece of the Antibody Puzzle: Observations from the HALT study\\.

PubMed

Snyder, Laurie D; Tinckam, Kathryn J

2018-06-04

In the rapidly evolving domain of clinical transplantation immunobiology, the interrogation and interpretation of HLA antibodies and their associated clinical consequences are in the spotlight. In lung transplant, HLA antibodies, in particular donor specific antibodies (DSA), are a determining component of the lung transplant antibody mediated rejection (AMR) definition (1). DSA after lung transplant are widely regarded as poor prognosticator, though sparse data to date necessitate ongoing discourse and continued investigation into incidence, timing and treatment. Prior studies reported a wide range of DSA incidence with differing consequences on a background of highly variable timing, methods, antibody analytic strategies and clinical definitions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Mitral Transcatheter Technologies

PubMed Central

Maisano, Francesco; Buzzatti, Nicola; Taramasso, Maurizio; Alfieri, Ottavio

2013-01-01

Mitral valve regurgitation (MR) is often diagnosed in patients with heart failure and is associated with worsening of symptoms and reduced survival. While surgery remains the gold standard treatment in low-risk patients with degenerative MR, in high-risk patients and in those with functional MR, transcatheter procedures are emerging as an alternative therapeutic option. MitraClip® is the device with which the largest clinical experience has been gained to date, as it offers sustained clinical benefit in selected patients. Further to MitraClip implantation, several additional approaches are developing, to better match with the extreme variability of mitral valve disease. Not only repair is evolving, initial steps towards percutaneous mitral valve implantation have already been undertaken, and initial clinical experience has just started. PMID:23908865

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

PubMed

Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

2016-07-01

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical and hematologic variables in ponies with experimentally induced equine ehrlichial colitis (Potomac horse fever).

PubMed

Ziemer, E L; Whitlock, R H; Palmer, J E; Spencer, P A

1987-01-01

The clinical and hematologic variables of 10 ponies with experimentally induced equine ehrlichial colitis (EEC; syn: Potomac horse fever) were studied for a 30-day period (6 ponies) or until death (4 ponies). The earliest clinical sign indicative of EEC was fever (rectal temperature exceeding 39 C). All ponies became depressed (CNS) at various times during the disease, and 90% of the ponies developed diarrhea between 9 and 15 days after infection was induced. The most significant hematologic change was an increase in plasma protein concentration after the onset of fever (P less than 0.05). The PCV in all ponies became increased above base line during the diarrheic phase of EEC. Forty percent of the ponies developed anemia (PCV less than or equal to 23%) during the study. White blood cell counts were highly variable, with 80% of the ponies developing leukopenia (WBC less than 5,000/microliters) during the illness and 60% of the ponies developing leukocytosis (WBC greater than 14,000/microliters) after leukopenia was observed. Differential WBC changes varied widely and included neutropenia with a left shift, lymphopenia, and eosinopenia. Serial thrombocyte counts, which were done for only 1 pony, identified the development of marked thrombocytopenia. Some hematologic changes in ponies with EEC were similar to those reported in canine monocytic and equine granulocytic ehrlichioses. These data are discussed in the context of the pathogenesis and differential diagnosis of EEC.

Head Circumference and Height in Autism

PubMed Central

Lainhart, Janet E.; Bigler, Erin D.; Bocian, Maureen; Coon, Hilary; Dinh, Elena; Dawson, Geraldine; Deutsch, Curtis K.; Dunn, Michelle; Estes, Annette; Tager-Flusberg, Helen; Folstein, Susan; Hepburn, Susan; Hyman, Susan; McMahon, William; Minshew, Nancy; Munson, Jeff; Osann, Kathy; Ozonoff, Sally; Rodier, Patricia; Rogers, Sally; Sigman, Marian; Spence, M. Anne; Stodgell, Christopher J.; Volkmar, Fred

2016-01-01

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI-R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research. PMID:17022081

What drives attitude towards telemedicine among families of pediatric patients? A survey.

PubMed

Russo, Luisa; Campagna, Ilaria; Ferretti, Beatrice; Agricola, Eleonora; Pandolfi, Elisabetta; Carloni, Emanuela; D'Ambrosio, Angelo; Gesualdo, Francesco; Tozzi, Alberto E

2017-01-17

Telemedicine has been recognized as a way to improve accessibility, quality, and efficiency of care. In view of the introduction of new telemedicine services, we conducted a survey through a self-administered questionnaire among families of children attending the Bambino Gesù Children's Hospital IRCCS, a tertiary care children's hospital located in Rome, Italy. We investigated sociodemographic data, clinical information, technological profile, attitude towards telemedicine, perceived advantages of telemedicine, fears regarding telemedicine, willingness to use a smartphone app providing telemedicine services and willingness to use a televisit service. Through logistic regression, we explored the effect of sociodemographic and clinical variables and technological profile on willingness of using a telemedicine app and a televisit service. We enrolled a total of 751 families. Most patients had a high technological profile, 81% had at least one account on a social network. Whatsapp was the most popular messaging service (76%). Seventy-two percent of patients would use an app for telemedicine services and 65% would perform a televisit. Owning a tablet was associated with both outcome variables - respectively: OR 2.216, 95% CI 1.358-3.616 (app) and OR 2.117, 95% CI 1.415-3.168 (televisit). Kind of hospitalization, diagnosis of a chronic disease, disease severity and distance from the health care center were not associated with the outcome variables. Families of pediatric patients with different clinical problems are keen to embark in telemedicine programs, independently from severity of disease or chronicity, and of distance from the hospital.

Treatment of scalp psoriasis with clobetasol-17 propionate 0.05% shampoo: a study on daily clinical practice.

PubMed

Bovenschen, H J; Van de Kerkhof, P C M

2010-04-01

Safety and clinical effectiveness of clobetasol-17 propionate 0.05% shampoo have been shown in patients with scalp psoriasis. First, to evaluate treatment satisfaction, user convenience safety and effectiveness of clobetasol-17 propionate 0.05% shampoo treatment in daily clinical practice. Second, to identify subgroup variables that may predict treatment success or failure. A total of 56 patients with scalp psoriasis were treated with short-contact clobetasol-17 propionate 0.05% shampoo once daily for 4 weeks. Data on treatment satisfaction, user convenience, safety and effectiveness were assessed on a 7-point Likert scale using postal questionnaires. Subgroup analyses were performed to identify variables that may predict treatment outcome. A total of 41 patients returned both questionnaires (73%). Positive treatment satisfaction and user convenience were reported by 66% and 79% of patients respectively. Patient-rated indicators for disease severity improved by 39-46% (P < 0.05%). No major side-effects were reported. Subgroup analyses did not reveal any statistically significant patient variable that may predict treatment outcome. However, a tendency towards improved treatment satisfaction was observed in patients who had received fewer topical antipsoriatic treatments previously (P > 0.05). Short-contact treatment with clobetasol-17 propionate 0.05% shampoo has high user convenience and patient satisfaction rates. Moreover, the treatment is well-tolerated and efficacious from patients' perspective. Subgroup analyses did not reveal factors predicting treatment outcome, although treatment success tended to be more evident in patients who had received fewer treatments previously.

Distal embolization during native vessel and vein graft coronary intervention with a vascular protection device: predictors of high-risk lesions.

PubMed

El-Jack, Seif S; Suwatchai, Pornratanarangsi; Stewart, James T; Ruygrok, Peter N; Ormiston, John A; West, Teena; Webster, Mark W I

2007-12-01

We sought to define clinical and angiographic variables that may predict patients and lesions at increased risk for distal embolism during percutaneous intervention (PCI), as assessed by debris retrieval from a distal-protection filter device. Distal thrombo- and atheroembolism may contribute to periprocedural myocardial necrosis during PCI, which may in turn affect long-term outcomes. Distal protection devices have been used to reduce this occurrence with variable outcomes depending on lesion and patient subsets. 194 consecutive patients in whom the FilterWire(R) device (FW) [Boston Scientific Corp., Natick, MA] was used for native coronary vessel (n =129) or vein graft (n = 65) PCI were studied. FW debris was visually analyzed using a semi-quantitative grading score. Patients with "significant" debris (particles > or = 1 mm diameter) were compared with those with "nonsignificant" debris (no debris or particles <1 mm) with respect to clinical (age, gender, coronary disease risk factors, clinical presentation, periprocedural medications), and angiographic (vessel treated, vessel size, lesion length, lesion characteristics, angiographic thrombus and TIMI flow before and after PCI) variables. Significant debris was retrieved in 55% of patients, more frequently from vein graft (69%) than native vessel lesions (48%, p = 0.006). No clinical characteristics predicted significant debris retrieval. Angiographic predictors of significant debris by multivariate analysis were longer stent length and final TIMI flow <3 (p = 0.009 and 0.007, respectively). Longer stent length, likely reflecting increased lesion length and plaque burden, predicted significant distal embolism during PCI in native vessel and vein graft lesions, as assessed by debris collected in a distal vascular protection device. This suggests that use of vascular protection devices should be considered during PCI of long lesions.

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi

PubMed Central

Alamgir, Muhammad Mohiuddin; Jamal, Qamar; Mirza, Talat

2016-01-01

Objective: To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. Methods: The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. Results: The patient’s population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41–50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. Conclusions: Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases. PMID:27375712

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi.

PubMed

Alamgir, Muhammad Mohiuddin; Jamal, Qamar; Mirza, Talat

2016-01-01

To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. The patient's population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases.

Accuracy, calibration and clinical performance of the EuroSCORE: can we reduce the number of variables?

PubMed

Ranucci, Marco; Castelvecchio, Serenella; Menicanti, Lorenzo; Frigiola, Alessandro; Pelissero, Gabriele

2010-03-01

The European system for cardiac operative risk evaluation (EuroSCORE) is currently used in many institutions and is considered a reference tool in many countries. We hypothesised that too many variables were included in the EuroSCORE using limited patient series. We tested different models using a limited number of variables. A total of 11150 adult patients undergoing cardiac operations at our institution (2001-2007) were retrospectively analysed. The 17 risk factors composing the EuroSCORE were separately analysed and ranked for accuracy of prediction of hospital mortality. Seventeen models were created by progressively including one factor at a time. The models were compared for accuracy with a receiver operating characteristics (ROC) analysis and area under the curve (AUC) evaluation. Calibration was tested with Hosmer-Lemeshow statistics. Clinical performance was assessed by comparing the predicted with the observed mortality rates. The best accuracy (AUC 0.76) was obtained using a model including only age, left ventricular ejection fraction, serum creatinine, emergency operation and non-isolated coronary operation. The EuroSCORE AUC (0.75) was not significantly different. Calibration and clinical performance were better in the five-factor model than in the EuroSCORE. Only in high-risk patients were 12 factors needed to achieve a good performance. Including many factors in multivariable logistic models increases the risk for overfitting, multicollinearity and human error. A five-factor model offers the same level of accuracy but demonstrated better calibration and clinical performance. Models with a limited number of factors may work better than complex models when applied to a limited number of patients. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Optimal auxiliary-covariate-based two-phase sampling design for semiparametric efficient estimation of a mean or mean difference, with application to clinical trials.

PubMed

Gilbert, Peter B; Yu, Xuesong; Rotnitzky, Andrea

2014-03-15

To address the objective in a clinical trial to estimate the mean or mean difference of an expensive endpoint Y, one approach employs a two-phase sampling design, wherein inexpensive auxiliary variables W predictive of Y are measured in everyone, Y is measured in a random sample, and the semiparametric efficient estimator is applied. This approach is made efficient by specifying the phase two selection probabilities as optimal functions of the auxiliary variables and measurement costs. While this approach is familiar to survey samplers, it apparently has seldom been used in clinical trials, and several novel results practicable for clinical trials are developed. We perform simulations to identify settings where the optimal approach significantly improves efficiency compared to approaches in current practice. We provide proofs and R code. The optimality results are developed to design an HIV vaccine trial, with objective to compare the mean 'importance-weighted' breadth (Y) of the T-cell response between randomized vaccine groups. The trial collects an auxiliary response (W) highly predictive of Y and measures Y in the optimal subset. We show that the optimal design-estimation approach can confer anywhere between absent and large efficiency gain (up to 24 % in the examples) compared to the approach with the same efficient estimator but simple random sampling, where greater variability in the cost-standardized conditional variance of Y given W yields greater efficiency gains. Accurate estimation of E[Y | W] is important for realizing the efficiency gain, which is aided by an ample phase two sample and by using a robust fitting method. Copyright © 2013 John Wiley & Sons, Ltd.

Optimal Auxiliary-Covariate Based Two-Phase Sampling Design for Semiparametric Efficient Estimation of a Mean or Mean Difference, with Application to Clinical Trials

PubMed Central

Gilbert, Peter B.; Yu, Xuesong; Rotnitzky, Andrea

2014-01-01

To address the objective in a clinical trial to estimate the mean or mean difference of an expensive endpoint Y, one approach employs a two-phase sampling design, wherein inexpensive auxiliary variables W predictive of Y are measured in everyone, Y is measured in a random sample, and the semi-parametric efficient estimator is applied. This approach is made efficient by specifying the phase-two selection probabilities as optimal functions of the auxiliary variables and measurement costs. While this approach is familiar to survey samplers, it apparently has seldom been used in clinical trials, and several novel results practicable for clinical trials are developed. Simulations are performed to identify settings where the optimal approach significantly improves efficiency compared to approaches in current practice. Proofs and R code are provided. The optimality results are developed to design an HIV vaccine trial, with objective to compare the mean “importance-weighted” breadth (Y) of the T cell response between randomized vaccine groups. The trial collects an auxiliary response (W) highly predictive of Y, and measures Y in the optimal subset. We show that the optimal design-estimation approach can confer anywhere between absent and large efficiency gain (up to 24% in the examples) compared to the approach with the same efficient estimator but simple random sampling, where greater variability in the cost-standardized conditional variance of Y given W yields greater efficiency gains. Accurate estimation of E[Y∣W] is important for realizing the efficiency gain, which is aided by an ample phase-two sample and by using a robust fitting method. PMID:24123289

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

PubMed Central

Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Salva, Katrin A.; Wood, Gary S.; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Pulitzer, Melissa; Advani, Ranjana H.; Horwitz, Steven M.

2015-01-01

Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. PMID:26195720

From vital signs to clinical outcomes for patients with sepsis: a machine learning basis for a clinical decision support system

PubMed Central

Gultepe, Eren; Green, Jeffrey P; Nguyen, Hien; Adams, Jason; Albertson, Timothy; Tagkopoulos, Ilias

2014-01-01

Objective To develop a decision support system to identify patients at high risk for hyperlactatemia based upon routinely measured vital signs and laboratory studies. Materials and methods Electronic health records of 741 adult patients at the University of California Davis Health System who met at least two systemic inflammatory response syndrome criteria were used to associate patients’ vital signs, white blood cell count (WBC), with sepsis occurrence and mortality. Generative and discriminative classification (naïve Bayes, support vector machines, Gaussian mixture models, hidden Markov models) were used to integrate heterogeneous patient data and form a predictive tool for the inference of lactate level and mortality risk. Results An accuracy of 0.99 and discriminability of 1.00 area under the receiver operating characteristic curve (AUC) for lactate level prediction was obtained when the vital signs and WBC measurements were analysed in a 24 h time bin. An accuracy of 0.73 and discriminability of 0.73 AUC for mortality prediction in patients with sepsis was achieved with only three features: median of lactate levels, mean arterial pressure, and median absolute deviation of the respiratory rate. Discussion This study introduces a new scheme for the prediction of lactate levels and mortality risk from patient vital signs and WBC. Accurate prediction of both these variables can drive the appropriate response by clinical staff and thus may have important implications for patient health and treatment outcome. Conclusions Effective predictions of lactate levels and mortality risk can be provided with a few clinical variables when the temporal aspect and variability of patient data are considered. PMID:23959843

Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

PubMed

Feletar, Marie; Hall, Stephen; Bird, Paul

2016-01-01

To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

Molecular classification of idiopathic pulmonary fibrosis: personalized medicine, genetics and biomarkers.

PubMed

Hambly, Nathan; Shimbori, Chiko; Kolb, Martin

2015-10-01

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease associated with high morbidity and poor survival. Characterized by substantial disease heterogeneity, the diagnostic considerations, clinical course and treatment response in individual patients can be variable. In the past decade, with the advent of high-throughput proteomic and genomic technologies, our understanding of the pathogenesis of IPF has greatly improved and has led to the recognition of novel treatment targets and numerous putative biomarkers. Molecular biomarkers with mechanistic plausibility are highly desired in IPF, where they have the potential to accelerate drug development, facilitate early detection in susceptible individuals, improve prognostic accuracy and inform treatment recommendations. Although the search for candidate biomarkers remains in its infancy, attractive targets such as MUC5B and MPP7 have already been validated in large cohorts and have demonstrated their potential to improve clinical predictors beyond that of routine clinical practices. The discovery and implementation of future biomarkers will face many challenges, but with strong collaborative efforts among scientists, clinicians and the industry the ultimate goal of personalized medicine may be realized. © 2015 Asian Pacific Society of Respirology.

Physiological and behavioral indices of emotion dysregulation as predictors of outcome from cognitive behavioral therapy and acceptance and commitment therapy for anxiety.

PubMed

Davies, Carolyn D; Niles, Andrea N; Pittig, Andre; Arch, Joanna J; Craske, Michelle G

2015-03-01

Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Commentary: Factors predicting family court decisions in high-conflict divorce.

PubMed

Stover, Carla Smith

2013-01-01

Factors that predict custody and visitation decisions are an important area of research, especially in the context of high-conflict divorce. In these cases, youths are at significantly higher risk for exposure to ongoing conflict, violence, and triangulation in their parents' disputes. What variables courts and evaluation clinics use to make custody decisions and whether they are the most salient requires further study. The work by Raub and colleagues in this issue extends our understanding of important factors considered by the courts and custody evaluators in high-conflict divorce and points to directions for future research in this area.

[A primer on Wilson disease for the general practitioner].

PubMed

Hiroz, Philippe; Antonino, Anca; Doerig, Christopher; Pache, Isabelle; Moradpour, Darius

2011-09-07

Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.

Automated Detection of Actinic Keratoses in Clinical Photographs

PubMed Central

Hames, Samuel C.; Sinnya, Sudipta; Tan, Jean-Marie; Morze, Conrad; Sahebian, Azadeh; Soyer, H. Peter; Prow, Tarl W.

2015-01-01

Background Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. Objective The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. Methods Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. Results The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. Conclusions The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face. PMID:25615930

Does nutrition support have a role in managing cancer cachexia?

PubMed

Laviano, Alessandro; Di Lazzaro Giraldi, Gianluca; Koverech, Angela

2016-12-01

Cachexia is a negative prognostic factor in cancer patients. The pathogenesis is related to a variable combination of reduced food intake and metabolic changes. However, whether nutritional support may contribute to effectively prevent and treat cachexia remains a debated issue. Consistent evidence demonstrates that anabolic windows of opportunity occur during the clinical trajectory of cancer patients. Also, the use of specific nutrients, namely omega-3 fatty acids, may enhance the efficacy of nutritional support when tumor-driven inflammatory response is high. Of greater interest, it is now becoming clearer that the use of nutritional support at key time points in the clinical journey of cancer patients (i.e., perioperative period) may extend its clinical benefits beyond those on nutritional status. Nutritional support plays a role in managing cancer cachexia, when it is timely delivered, when it provides adequate amounts of calories and proteins, and when it is part of a concurrent palliative care approach. Specific nutrients, that is, omega-3 fatty acids, may help in those cancer patients with high-inflammatory response, and may also contribute to positively influence long-term clinical outcomes.

Expressed emotion is not associated with disorder severity in first-episode mental disorder.

PubMed

Heikkilä, Jyrki; Karlsson, Hasse; Taiminen, Tero; Lauerma, Hannu; Ilonen, Tuula; Leinonen, Kirsi-Marja; Wallenius, Elina; Virtanen, Hilkka; Heinimaa, Markus; Koponen, Salla; Jalo, Päivi; Kaljonen, Anne; Salakangas, Raimo K R

2002-08-30

A family atmosphere characterized by expressed emotion (EE) is a robust predictor of clinical outcome of patients with schizophrenia and mood disorders. However, there is ongoing discussion as to whether EE is more a cause of clinical outcome or a parental reaction to disorder severity. This cross-sectional study examines a sample of 42 consecutive first-episode patients from a defined geographical area with severe mental disorders (schizophrenia-related disorders, psychotic mood disorders, and non-psychotic mood disorders). Their 42 relatives were interviewed, and the relationships between EE variables derived with the five-minute speech sample method (FMSS) and the patients' demographic, premorbid and clinical measures were analyzed. A high EE score was found in 40% of the relatives. High EE was associated with the interviewed relative's not being a spouse and the patient's being young and unmarried. It was not associated with premorbid characteristics, symptom dimensions or the diagnostic group of the patient. These results do not support the hypothesis that EE is a reaction to the clinical features of the patient. Instead, demographic factors may partly mediate the effect of EE on prognosis.

Heart failure in primary care: co-morbidity and utilization of health care resources.

PubMed

Carmona, Montserrat; García-Olmos, Luis M; García-Sagredo, Pilar; Alberquilla, Ángel; López-Rodríguez, Fernando; Pascual, Mario; Muñoz, Adolfo; Salvador, Carlos H; Monteagudo, José L; Otero-Puime, Ángel

2013-10-01

In order to ensure proper management of primary care (PC) services, the efficiency of the health professionals tasked with such services must be known. Patients with heart failure (HF) are characterized by advanced age, high co-morbidity and high resource utilization. To ascertain PC resource utilization by HF patients and variability in the management of such patients by GPs. Descriptive, cross-sectional study targeting a population attended by 129 GPs over the course of 1 year. All patients with diagnosis of HF in their clinical histories were included, classified using the Adjusted Clinical Group system and then grouped into six resource utilization bands (RUBs). Resource utilization and Efficiency Index were both calculated. One hundred per cent of patients with HF were ranked in RUBs 3, 4 and 5. The highest GP visit rate was 20 and the lowest in excess of 10 visits per year. Prescription drug costs for these patients ranged from €885 to €1422 per patient per year. Health professional efficiency varied notably, even after adjustment for co-morbidity (Efficiency Index Variation Ratio of 28.27 for visits and 404.29 for prescription drug cost). Patients with HF register a high utilization of resources, and there is great variability in the management of such patients by health professionals, which cannot be accounted for by the degree of case complexity.

Using hypnosis to disrupt face processing: mirrored-self misidentification delusion and different visual media

PubMed Central

Connors, Michael H.; Barnier, Amanda J.; Coltheart, Max; Langdon, Robyn; Cox, Rochelle E.; Rivolta, Davide; Halligan, Peter W.

2014-01-01

Mirrored-self misidentification delusion is the belief that one’s reflection in the mirror is not oneself. This experiment used hypnotic suggestion to impair normal face processing in healthy participants and recreate key aspects of the delusion in the laboratory. From a pool of 439 participants, 22 high hypnotisable participants (“highs”) and 20 low hypnotisable participants were selected on the basis of their extreme scores on two separately administered measures of hypnotisability. These participants received a hypnotic induction and a suggestion for either impaired (i) self-face recognition or (ii) impaired recognition of all faces. Participants were tested on their ability to recognize themselves in a mirror and other visual media – including a photograph, live video, and handheld mirror – and their ability to recognize other people, including the experimenter and famous faces. Both suggestions produced impaired self-face recognition and recreated key aspects of the delusion in highs. However, only the suggestion for impaired other-face recognition disrupted recognition of other faces, albeit in a minority of highs. The findings confirm that hypnotic suggestion can disrupt face processing and recreate features of mirrored-self misidentification. The variability seen in participants’ responses also corresponds to the heterogeneity seen in clinical patients. An important direction for future research will be to examine sources of this variability within both clinical patients and the hypnotic model. PMID:24994973

CBCT-based bone quality assessment: are Hounsfield units applicable?

PubMed Central

Jacobs, R; Singer, S R; Mupparapu, M

2015-01-01

CBCT is a widely applied imaging modality in dentistry. It enables the visualization of high-contrast structures of the oral region (bone, teeth, air cavities) at a high resolution. CBCT is now commonly used for the assessment of bone quality, primarily for pre-operative implant planning. Traditionally, bone quality parameters and classifications were primarily based on bone density, which could be estimated through the use of Hounsfield units derived from multidetector CT (MDCT) data sets. However, there are crucial differences between MDCT and CBCT, which complicates the use of quantitative gray values (GVs) for the latter. From experimental as well as clinical research, it can be seen that great variability of GVs can exist on CBCT images owing to various reasons that are inherently associated with this technique (i.e. the limited field size, relatively high amount of scattered radiation and limitations of currently applied reconstruction algorithms). Although attempts have been made to correct for GV variability, it can be postulated that the quantitative use of GVs in CBCT should be generally avoided at this time. In addition, recent research and clinical findings have shifted the paradigm of bone quality from a density-based analysis to a structural evaluation of the bone. The ever-improving image quality of CBCT allows it to display trabecular bone patterns, indicating that it may be possible to apply structural analysis methods that are commonly used in micro-CT and histology. PMID:25315442

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders

PubMed Central

Conelea, Christine A.; Wellen, Brianna; Woods, Douglas W.; Greene, Deanna J.; Black, Kevin J.; Specht, Matthew; Himle, Michael B.; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression. PMID:29875706

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders.

PubMed

Conelea, Christine A; Wellen, Brianna; Woods, Douglas W; Greene, Deanna J; Black, Kevin J; Specht, Matthew; Himle, Michael B; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs.

PubMed

Censi, Roberta; Di Martino, Piera

2015-10-15

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

Impulsivity in bipolar disorders in a Tunisian sample.

PubMed

Feki, Ines; Moalla, Mariem; Baati, Imen; Trigui, Dorsaf; Sellami, Rim; Masmoudi, Jaweher

2016-08-01

Impulsivity as a trait characteristic is increased in bipolar disorder and may be a core factor of the illness. The objectives of our work are to evaluate the level of impulsivity among patients with bipolar disorder and to study its relation with mood state, alcohol misuse, suicide attempts and other socio-demographic and clinical factors. We measured impulsivity in 60 subjects with bipolar disorder in relationship to socio-demographic and clinical variables. The subjects completed Data included socio-demographic details and clinical variables, the Barratt Impulsiveness Scale (BIS-11) in an Arabic version to assess impulsivity, The Mini International Neuropsychiatric Interview "MINI" version 05 to screen for alcohol abuse or dependence and mood graphic rate scale (MGRS) to evaluate mood state. Our results show that the mean score of BIS-11 was 71.5. Fifty-five per cent of the patients had a high level of impulsiveness. No differences were found relating to mood state. Impulsivity was related to Male gender, lower educational level, early age of onset, smoking, alcohol and drug misuse and prior suicide attempts. The treatment of patients with BD should consider to reduce impulsivity to improve morbidity. Copyright © 2016 Elsevier B.V. All rights reserved.

Macro- and microperfusion during application of a new compression system, designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease.

PubMed

Jünger, Michael; Haase, Hermann; Schwenke, Linda; Bichel, Jens; Schuren, Jan; Ladwig, Andrea

2013-01-01

To investigate macro- and microperfusion during 14 days of treatment with a new 2-layer compression system (3M™ Coban™ 2 Lite), designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease. A single-centre, open-label, prospective pilot study was performed with 15 subjects suffering from peripheral arterial occlusive disease with an ankle brachial pressure index (ABPI) of 0.5-0.8, who volunteered to have their 'study leg' bandaged with the new system. Coincident leg ulcer or chronic venous disease was not mandatory. All subjects received the new compression system, which stayed in place from 1 up to 4 days according to scheduled study visits. The system was reapplied by study personnel at each clinical visit (days 1, 2, 3, 4, 7, 10 and 14). The study participation stopped after 14 days. At each clinical visit safety assessments were performed: measurement of acral pulsation to capture macroperfusion; laser Doppler fluxmetry to capture microperfusion; clinical signs of pressure related skin damage, hypoxia-related pain and sub-bandage pressure measurement. In addition, the leg volume was measured and a comfort questionnaire was completed. An average sub-bandage pressure in standing position of approximately 30 mmHg was measured at the B1 location immediately after bandage application. Laser Doppler fluxmetry demonstrated positive effects on microcirculation regarding vasomotion and respiratory reflux. No change of the cardiac signal appeared. For acrale pulsations a high intraindividual variability was found with no clear interference to the bandage application. No pressure-related skin damage or hypoxia-related pain was detected. After application of the new compression system in subjects with moderate PAOD, laser Doppler fluxmetry indicated significant improvements of the microcirculation. High variability and lack of correlation to clinical symptoms was found for the acral pulsation. The new compression system revealed a high grade of tolerability and a good safety profile.

A partner-related risk behavior index to identify people at elevated risk for sexually transmitted infections.

PubMed

Crosby, Richard; Shrier, Lydia A

2013-04-01

The purpose of this study was to develop and test a sexual-partner-related risk behavior index to identify high-risk individuals most likely to have a sexually transmitted infection (STI). Patients from five STI and adolescent medical clinics in three US cities were recruited (N = 928; M age = 29.2 years). Data were collected using audio-computer-assisted self-interviewing. Of seven sexual-partner-related variables, those that were significantly associated with the outcomes were combined into a partner-related risk behavior index. The dependent variables were laboratory-confirmed infection with Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. Nearly one-fifth of the sample (169/928; 18.4%) tested positive for an STI. Three of the seven items were significantly associated with having one or more STIs: sex with a newly released prisoner, sex with a person known or suspected of having an STI, and sexual concurrency. In combined form, this three-item index was significantly associated with STI prevalence (p < .001). In the presence of three covariates (gender, race, and age), those classified as being at-risk by the index were 1.8 times more likely than those not classified as such to test positive for an STI (p < .001). Among individuals at risk for STIs, a three-item index predicted testing positive for one or more of three STIs. This index could be used to prioritize and guide intensified clinic-based counseling for high-risk patients of STI and other clinics.

Schizotypy and specificity of negative emotions on an emotional Stroop paradigm in the general population.

PubMed

Yaffe, Beril; Walder, Deborah J

2016-05-30

Attentional-interference using emotional Stroop tasks (ESTs) is greater among individuals in the general population with positive (versus negative) schizotypal traits; specifically in response to negatively (versus positively) valenced words, potentially capturing threat-sensitivity. Variability in attentional-interference as a function of subcategories of negatively valenced words (and in relation to schizotypal traits) remains underexplored in EST studies. We examined attentional-interference across negative word subcategories (fear/anger/sadness/disgust), and in relation to positive schizotypy, among non-clinical individuals in the general population reporting varying degrees of schizotypal traits. As hypothesized, performance differed across word subcategories, though the pattern varied from expectation. Attentional-interference was greater for fear and sadness compared to anger; and analogous for fear, disgust, and sadness. In the high schizotypy group, positive schizotypal traits were directly associated with attentional-interference to disgust. Attentional-interference was comparable between high- and low-positive schizotypy. Results suggest negative emotion subcategories may differentially reflect threat-sensitivity. Disgust-sensitivity may be particularly salient in (non-clinical) positive schizotypy. Findings have implications for understanding negative emotion specificity and variability in stimulus presentation modality when studying threat-related attentional-interference. Finally, disgust-related attentional-interference may serve as a cognitive correlate of (non-clinical) positive schizotypy. Expanding this research to prodromal populations will help explore disgust-related attentional-interference as a potential cognitive marker of positive symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Financial Management of a Large Multi-site Randomized Clinical Trial

PubMed Central

Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

gHRV: Heart rate variability analysis made easy.

PubMed

Rodríguez-Liñares, L; Lado, M J; Vila, X A; Méndez, A J; Cuesta, P

2014-08-01

In this paper, the gHRV software tool is presented. It is a simple, free and portable tool developed in python for analysing heart rate variability. It includes a graphical user interface and it can import files in multiple formats, analyse time intervals in the signal, test statistical significance and export the results. This paper also contains, as an example of use, a clinical analysis performed with the gHRV tool, namely to determine whether the heart rate variability indexes change across different stages of sleep. Results from tests completed by researchers who have tried gHRV are also explained: in general the application was positively valued and results reflect a high level of satisfaction. gHRV is in continuous development and new versions will include suggestions made by testers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic mutations in Gorlin-Goltz syndrome

PubMed Central

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-01-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. PMID:24339558

Genetic mutations in Gorlin-Goltz syndrome.

PubMed

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-07-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management.

Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study

USDA-ARS?s Scientific Manuscript database

Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clin...

Accuracy and variability of tumor burden measurement on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Salarian, Mehrnoush; Gibson, Eli; Shahedi, Maysam; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Romagnoli, Cesare; Cool, Derek W.; Bastian-Jordan, Matthew; Chin, Joseph L.; Pautler, Stephen; Bauman, Glenn S.; Ward, Aaron D.

2014-03-01

Measurement of prostate tumour volume can inform prognosis and treatment selection, including an assessment of the suitability and feasibility of focal therapy, which can potentially spare patients the deleterious side effects of radical treatment. Prostate biopsy is the clinical standard for diagnosis but provides limited information regarding tumour volume due to sparse tissue sampling. A non-invasive means for accurate determination of tumour burden could be of clinical value and an important step toward reduction of overtreatment. Multi-parametric magnetic resonance imaging (MPMRI) is showing promise for prostate cancer diagnosis. However, the accuracy and inter-observer variability of prostate tumour volume estimation based on separate expert contouring of T2-weighted (T2W), dynamic contrastenhanced (DCE), and diffusion-weighted (DW) MRI sequences acquired using an endorectal coil at 3T is currently unknown. We investigated this question using a histologic reference standard based on a highly accurate MPMRIhistology image registration and a smooth interpolation of planimetric tumour measurements on histology. Our results showed that prostate tumour volumes estimated based on MPMRI consistently overestimated histological reference tumour volumes. The variability of tumour volume estimates across the different pulse sequences exceeded interobserver variability within any sequence. Tumour volume estimates on DCE MRI provided the lowest inter-observer variability and the highest correlation with histology tumour volumes, whereas the apparent diffusion coefficient (ADC) maps provided the lowest volume estimation error. If validated on a larger data set, the observed correlations could support the development of automated prostate tumour volume segmentation algorithms as well as correction schemes for tumour burden estimation on MPMRI.

Clustering of metabolic and cardiovascular risk factors in the polycystic ovary syndrome: a principal component analysis.

PubMed

Stuckey, Bronwyn G A; Opie, Nicole; Cussons, Andrea J; Watts, Gerald F; Burke, Valerie

2014-08-01

Polycystic ovary syndrome (PCOS) is a prevalent condition with heterogeneity of clinical features and cardiovascular risk factors that implies multiple aetiological factors and possible outcomes. To reduce a set of correlated variables to a smaller number of uncorrelated and interpretable factors that may delineate subgroups within PCOS or suggest pathogenetic mechanisms. We used principal component analysis (PCA) to examine the endocrine and cardiometabolic variables associated with PCOS defined by the National Institutes of Health (NIH) criteria. Data were retrieved from the database of a single clinical endocrinologist. We included women with PCOS (N = 378) who were not taking the oral contraceptive pill or other sex hormones, lipid lowering medication, metformin or other medication that could influence the variables of interest. PCA was performed retaining those factors with eigenvalues of at least 1.0. Varimax rotation was used to produce interpretable factors. We identified three principal components. In component 1, the dominant variables were homeostatic model assessment (HOMA) index, body mass index (BMI), high density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL) cholesterol and triglycerides; in component 3, total testosterone and LH/FSH ratio. These components explained 37%, 13% and 11% of the variance in the PCOS cohort respectively. Multiple correlated variables from patients with PCOS can be reduced to three uncorrelated components characterised by insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering of risk factors is consistent with different pathogenetic pathways within PCOS and/or differing cardiometabolic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of three-dimensional multi-segmental foot models used in clinical gait laboratories.

PubMed

Nicholson, Kristen; Church, Chris; Takata, Colton; Niiler, Tim; Chen, Brian Po-Jung; Lennon, Nancy; Sees, Julie P; Henley, John; Miller, Freeman

2018-05-16

Many skin-mounted three-dimensional multi-segmented foot models are currently in use for gait analysis. Evidence regarding the repeatability of models, including between trial and between assessors, is mixed, and there are no between model comparisons of kinematic results. This study explores differences in kinematics and repeatability between five three-dimensional multi-segmented foot models. The five models include duPont, Heidelberg, Oxford Child, Leardini, and Utah. Hind foot, forefoot, and hallux angles were calculated with each model for ten individuals. Two physical therapists applied markers three times to each individual to assess within and between therapist variability. Standard deviations were used to evaluate marker placement variability. Locally weighted regression smoothing with alpha-adjusted serial T tests analysis was used to assess kinematic similarities. All five models had similar variability, however, the Leardini model showed high standard deviations in plantarflexion/dorsiflexion angles. P-value curves for the gait cycle were used to assess kinematic similarities. The duPont and Oxford models had the most similar kinematics. All models demonstrated similar marker placement variability. Lower variability was noted in the sagittal and coronal planes compared to rotation in the transverse plane, suggesting a higher minimal detectable change when clinically considering rotation and a need for additional research. Between the five models, the duPont and Oxford shared the most kinematic similarities. While patterns of movement were very similar between all models, offsets were often present and need to be considered when evaluating published data. Copyright © 2018 Elsevier B.V. All rights reserved.

Screening for periodontal disease in research dogs - a methodology study.

PubMed

Kortegaard, Hanne E; Eriksen, Thomas; Baelum, Vibeke

2014-11-19

It has been shown that the prevalence of both clinical attachment loss (CAL) ≥1 mm and pocket probing depth (PPD) ≥4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence, a minority of dogs carry the major PD burden. These epidemiological features suggest that screening for PD in larger groups of dogs, allowing for rapid assessment of treatment planning, or for the selection of dogs with or without PD prior to be included in experimental trials, should be possible. CAL is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle dogs was to construct a fast, simple and accurate screening tool, which is highly sensitive for the identification of dogs with PD. Examination of the maxillary P4, P3, P2, I1 and C would, in this population, result in the identification of 85.5% of all dogs and 96% of all teeth positive for CAL ≥1 mm, and 58.9% of all dogs and 82.1% of all teeth positive for PD ≥4 mm. Examination of tooth pairs, all C's, maxillary I2, M2 and the mandibular P4 would, in this population result in identification of 92.9% of all dogs and 97.3% of all teeth positive for PD ≥4 mm, and 65.5% of all dogs and 83.2% of all teeth positive for CAL ≥1 mm. The results presented here only pertain to the present study population. This screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree of sensitivity. Before this screening can be used in clinical practice, it has to be validated in breeds other than Beagle dogs and in populations with larger age variation.

Long-term cortisol measures predict Alzheimer disease risk.

PubMed

Ennis, Gilda E; An, Yang; Resnick, Susan M; Ferrucci, Luigi; O'Brien, Richard J; Moffat, Scott D

2017-01-24

To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD. © 2016 American Academy of Neurology.

Clinical Practice Guideline Implementation Strategy Patterns in Veterans Affairs Primary Care Clinics

PubMed Central

Hysong, Sylvia J; Best, Richard G; Pugh, Jacqueline A

2007-01-01

Background The Department of Veterans Affairs (VA) mandated the system-wide implementation of clinical practice guidelines (CPGs) in the mid-1990s, arming all facilities with basic resources to facilitate implementation; despite this resource allocation, significant variability still exists across VA facilities in implementation success. Objective This study compares CPG implementation strategy patterns used by high and low performing primary care clinics in the VA. Research Design Descriptive, cross-sectional study of a purposeful sample of six Veterans Affairs Medical Centers (VAMCs) with high and low performance on six CPGs. Subjects One hundred and two employees (management, quality improvement, clinic personnel) involved with guideline implementation at each VAMC primary care clinic. Measures Participants reported specific strategies used by their facility to implement guidelines in 1-hour semi-structured interviews. Facilities were classified as high or low performers based on their guideline adherence scores calculated through independently conducted chart reviews. Findings High performing facilities (HPFs) (a) invested significantly in the implementation of the electronic medical record and locally adapting it to provider needs, (b) invested dedicated resources to guideline-related initiatives, and (c) exhibited a clear direction in their strategy choices. Low performing facilities exhibited (a) earlier stages of development for their electronic medical record, (b) reliance on preexisting resources for guideline implementation, with little local adaptation, and (c) no clear direction in their strategy choices. Conclusion A multifaceted, yet targeted, strategic approach to guideline implementation emphasizing dedicated resources and local adaptation may result in more successful implementation and higher guideline adherence than relying on standardized resources and taxing preexisting channels. PMID:17355583

Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

PubMed

Cleophas, Ton J

2016-01-01

Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample.

PubMed

Gutiérrez-Rojas, Luis; Jurado, Dolores; Martínez-Ortega, José María; Gurpegui, Manuel

2010-12-01

We analyzed the association of previous course-of-illness and other variables of clinical interest with a high frequency of both depressive or (hypo)manic episodes controlling for the effect of socio-demographic characteristics. A total of 108 outpatients with a DSM-IV diagnosis of bipolar disorder (BD) were recruited. A retrospective and naturalistic study was conducted to examine the number of affective episodes and their relationship with socio-demographic, clinical and course-of-illness variables, including adherence to medication, type of medication used and the use of addictive substances. The episode frequency was estimated as the number of "major instances" of depression, hypomania and mania during the illness. To classify the patients into two groups (higher and lower-episode frequency), we used the statistical criterion of median split. Results were analyzed with logistic regression models to control for the effects of potential confounders. A high episode frequency (nine or more episodes) was associated with age (36-55years), delay in diagnosis, poor adherence to medication and current use of antipsychotic medication. In addition, a high frequency of manic episodes (four or more) was associated with female sex, age (>36years) and a manic onset of the illness, whereas a high frequency of depressive episodes (five or more) was associated with delay in diagnosis and poor adherence to medication. Cross-sectional study design. Avoiding delay in diagnosis and enhancing treatment adherence might be important targets for reducing recurrences in BD. Copyright © 2010 Elsevier B.V. All rights reserved.

Automated extraction of clinical traits of multiple sclerosis in electronic medical records

PubMed Central

Davis, Mary F; Sriram, Subramaniam; Bush, William S; Denny, Joshua C; Haines, Jonathan L

2013-01-01

Objectives The clinical course of multiple sclerosis (MS) is highly variable, and research data collection is costly and time consuming. We evaluated natural language processing techniques applied to electronic medical records (EMR) to identify MS patients and the key clinical traits of their disease course. Materials and methods We used four algorithms based on ICD-9 codes, text keywords, and medications to identify individuals with MS from a de-identified, research version of the EMR at Vanderbilt University. Using a training dataset of the records of 899 individuals, algorithms were constructed to identify and extract detailed information regarding the clinical course of MS from the text of the medical records, including clinical subtype, presence of oligoclonal bands, year of diagnosis, year and origin of first symptom, Expanded Disability Status Scale (EDSS) scores, timed 25-foot walk scores, and MS medications. Algorithms were evaluated on a test set validated by two independent reviewers. Results We identified 5789 individuals with MS. For all clinical traits extracted, precision was at least 87% and specificity was greater than 80%. Recall values for clinical subtype, EDSS scores, and timed 25-foot walk scores were greater than 80%. Discussion and conclusion This collection of clinical data represents one of the largest databases of detailed, clinical traits available for research on MS. This work demonstrates that detailed clinical information is recorded in the EMR and can be extracted for research purposes with high reliability. PMID:24148554

Exploring correlates of diabetes-related stress among adults with Type 1 diabetes in the T1D exchange clinic registry.

PubMed

Boden, Matthew Tyler; Gala, Sasha

2018-04-01

To explore relations between diabetes-related stress and multiple sociodemographic, diabetes health, other health, and treatment-related variables among a large sample of adults with Type 1 Diabetes (T1D). The sample consisted of 10,821 adults (over 18 years old) enrolled in the T1D Exchange Clinic Registry. The T1D Exchange clinic network consists of 67 diabetes clinical centers throughout the United States selected to broadly represent pediatric and adult patients with T1D. Variables were assessed through participant self-report and extraction of clinic chart data. Univariate and multiple linear regression (with simultaneous entry of all predictors) analyses were conducted. Robustly associated with increased diabetes-related stress across analyses were multiple sociodemographic (female [vs. male], native Hawaiian/other Pacific islander [vs. white/Caucasian], decreased age and diabetes duration), diabetes health (higher HbA1c), other health (lower general health, presence of major life stress and depression, less physical activity), and treatment related variables (use of injections/pen or combination injection/pen/pump [vs. pump], use of CGM, increased frequency of missing insulin doses and BG checking, decreased frequency of BG checking prior to bolus, receipt of mental health treatment). We replicated and extended research demonstrating that diabetes-related stress among people with T1D occurs at higher levels among those with particular sociodemographic characteristics and is associated with a range poorer diabetes health and other health variables, and multiple treatment-related variables. The strong incremental prediction of diabetes-related stress by multiple variables in our study suggests that a multi-variable, personalized approach may increase the effectiveness of treatments for diabetes-related stress. Published by Elsevier B.V.

A New Understanding of Quality of Life in Children and Adolescents with Obesity: Contribution of the Self-determination Theory.

PubMed

Buttitta, Marie; Rousseau, Amélie; Guerrien, Alain

2017-12-01

Preservation of Quality of Life (QOL) is now a major determinant of obesity management, but little is known about variables predicting QOL. Identifying these predicting variables of QOL would provide further understanding of the QOL concept and help draw clinical implications. The Self-determination Theory (SDT) is a promising understanding perspective of the QOL. The SDT postulates that well-being and motivation are determined by the satisfaction of three needs: autonomy, competence, and relatedness. Many researches have confirmed the relationships between these SDT's needs and well-being, but this theory has little been applied to the problem of QOL in obese children and adolescents. Literature results and theoretical implications of the SDT in understanding of QOL in youth obesity are discussed. New clinical applications could be drawn: in children with obesity, interventions promoting high satisfaction of the SDT's needs could improve their QOL and help them break the vicious circles of overweight.

Heart Failure Clinical Trials in East and Southeast Asia: Understanding the Importance and Defining the Next Steps

PubMed Central

Mentz, Robert J.; Roessig, Lothar; Greenberg, Barry H.; Sato, Naoki; Shinagawa, Kaori; Yeo, Daniel; Kwok, Bernard W.K.; Reyes, Eugenio B.; Krum, Henry; Pieske, Burkert; Greene, Stephen J.; Ambrosy, Andrew P.; Kelly, Jacob P.; Zannad, Faiez; Pitt, Bertram; Lam, Carolyn S.P.

2016-01-01

Heart failure (HF) is a major and increasing global public health problem. In Asia, aging populations and recent increases in cardiovascular risk factors have contributed to a particularly high burden of HF with similarly poor outcomes compared to the rest of the world. Representation of Asians in landmark HF trials has been variable. In addition, HF patients from Asia demonstrate clinical differences from other geographic regions. Thus, the generalizability of some clinical trials results to the Asian population remains uncertain. In this manuscript, we review differences in the HF phenotype, management and outcomes in patients from East and Southeast Asia. We describe lessons learned in Asia from recent HF registries and clinical trial databases and outline strategies to improve the potential for success in future trials. This review is based on discussions between scientists, clinical trialists, industry representatives and regulatory representatives at the CardioVascular Clinical Trialist Asia Forum on July 4, 2014. PMID:27256745

Data management by using R: big data clinical research series.

PubMed

Zhang, Zhongheng

2015-11-01

Electronic medical record (EMR) system has been widely used in clinical practice. Instead of traditional record system by hand writing and recording, the EMR makes big data clinical research feasible. The most important feature of big data research is its real-world setting. Furthermore, big data research can provide all aspects of information related to healthcare. However, big data research requires some skills on data management, which however, is always lacking in the curriculum of medical education. This greatly hinders doctors from testing their clinical hypothesis by using EMR. To make ends meet, a series of articles introducing data management techniques are put forward to guide clinicians to big data clinical research. The present educational article firstly introduces some basic knowledge on R language, followed by some data management skills on creating new variables, recoding variables and renaming variables. These are very basic skills and may be used in every project of big data research.

Cost efficiency of university hospitals in the Nordic countries: a cross-country analysis.

PubMed

Medin, Emma; Anthun, Kjartan S; Häkkinen, Unto; Kittelsen, Sverre A C; Linna, Miika; Magnussen, Jon; Olsen, Kim; Rehnberg, Clas

2011-12-01

This paper estimates cost efficiency scores using the bootstrap bias-corrected procedure, including variables for teaching and research, for the performance of university hospitals in the Nordic countries. Previous research has shown that hospital provision of research and education interferes with patient care routines and inflates the costs of health care services, turning university hospitals into outliers in comparative productivity and efficiency analyses. The organisation of patient care, medical education and clinical research as well as available data at the university hospital level are highly similar in the Nordic countries, creating a data set of comparable decision-making units suitable for a cross-country cost efficiency analysis. The results demonstrate significant differences in university hospital cost efficiency when variables for teaching and research are entered into the analysis, both between and within the Nordic countries. The results of a second-stage analysis show that the most important explanatory variables are geographical location of the hospital and the share of discharges with a high case weight. However, a substantial amount of the variation in cost efficiency at the university hospital level remains unexplained.

Critical discussion of evaluation parameters for inter-observer variability in target definition for radiation therapy.

PubMed

Fotina, I; Lütgendorf-Caucig, C; Stock, M; Pötter, R; Georg, D

2012-02-01

Inter-observer studies represent a valid method for the evaluation of target definition uncertainties and contouring guidelines. However, data from the literature do not yet give clear guidelines for reporting contouring variability. Thus, the purpose of this work was to compare and discuss various methods to determine variability on the basis of clinical cases and a literature review. In this study, 7 prostate and 8 lung cases were contoured on CT images by 8 experienced observers. Analysis of variability included descriptive statistics, calculation of overlap measures, and statistical measures of agreement. Cross tables with ratios and correlations were established for overlap parameters. It was shown that the minimal set of parameters to be reported should include at least one of three volume overlap measures (i.e., generalized conformity index, Jaccard coefficient, or conformation number). High correlation between these parameters and scatter of the results was observed. A combination of descriptive statistics, overlap measure, and statistical measure of agreement or reliability analysis is required to fully report the interrater variability in delineation.

Adherence to AIOM (Italian Association of Medical Oncology) lung cancer guidelines in Italian clinical practice: Results from the RIGHT-3 (research for the identification of the most effective and highly accepted clinical guidelines for cancer treatment) study.

PubMed

Barni, Sandro; Maiello, Evaristo; Di Maio, Massimo; Ardizzoni, Andrea; Cappuzzo, Federico; Maranzano, Ernesto; Novello, Silvia; Bennati, Chiara; Ori, Alessandra; Rizzoli, Sara; Crinò, Lucio

2015-11-01

Clinical practice guidelines represent a key tool to improve quality and reduce variability of cancer care. In 2004, Italian Association of Medical Oncology (AIOM) launched the RIGHT (research for the identification of the most effective and highly accepted clinical guidelines for cancer treatment) program. The third step, RIGHT-3, evaluated the concordance between AIOM lung cancer guidelines and Italian clinical practice. RIGHT-3 was a retrospective observational study, conducted in 53 Italian centers treating lung cancer. Sampling from AIOM database of 230 centers was stratified by presence of thoracic surgery and geographic distribution. To describe the adherence to AIOM guidelines (2009 edition), 11 indicators regarding diagnostic and treatment procedures were identified. Patients with non-small-cell lung cancer (NSCLC) diagnosis who had first visit in 2010 were divided into 3 groups, based on TNM stage: I-II-IIIA (5 indicators), IIIB (3 indicators) and IV (3 indicators). 708 patients were enrolled; 680 were eligible: 225 patients in stage I-II-IIIA; 156 patients in stage IIIB; 299 patients in stage IV. Cyto-histological diagnosis was available in 96%, 97%, 96% of stage I-II-IIIA, IIIB, IV respectively. Positron-emission tomography was performed in 64% of stage I-II-IIIA and 46% of stage IIIB. 88% of stage I-II patients eligible for surgery underwent lobectomy; after surgery, 61% of stage II and 57% of stage IIIA patients received adjuvant chemotherapy. Among stage IIIB patients who received combined chemo- radiotherapy, sequential approach was more common than concomitant treatment (86% vs. 14%). Among stage IV patients, 87% received platinum-based first-line treatment, and 70% received second-line. The RIGHT-3 study showed that, in 2010, adherence to Italian NSCLC guidelines was high for many indicators (including those related to treatment of stage IV patients), but lower for some diagnostic procedures. Guidelines adherence monitoring can be useful to reduce variability in cancer care. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.